psychiatryПСИХИАТРИЯPsychiatry (Moscow) (Psikhiatriya)1683-83192618-6667FSBSI “The Mental Health Research Centre”; LLC «Publisher «MIA»10.30629/2618-6667-2023-21-7-46-64psychiatry-1083Research ArticleНАУЧНЫЕ ОБЗОРЫSCIENTIFIC REVIEWSПрогениторы олигодендроцитов при шизофрении: патогенетическая роль и потенциальная мишень для терапииOligodendrocyte Progenitors in Schizophrenia: The Role in Pathogenesis and Potential Treatment Targethttps://orcid.org/0000-0003-3710-8456КоломеецН. С.KolomeetsN. S.

Наталья Степановна Коломеец, доктор биологических наук, ведущий научный сотрудник, лаборатория клинической нейроморфологии

Москва

Natalya S. Kolomeets, Dr. of Sci. (Biol.), Leading Researcher, Laboratory of Neuropathology

Moscow

ns-kolomeets@mail.ruФГБНУ «Научный центр психического здоровья»РоссияFSBSI “Mental Health Research Centre”Russian Federation2023310120242174664Copyright © Коломеец Н.С., 20242024Коломеец Н.С.Kolomeets N.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.journalpsychiatry.com/jour/article/view/1083

Обоснование: синдром нарушений межнейронных связей в мозге больных шизофренией тесно связан с выраженными нарушениями миелинизации в мозге пациентов, что подтверждается данными нейровизуалиционных исследований. Нарушения миелинизации мозга предполагают патологию клеток семейства олигодендроцитов (ОЛ). Особый интерес представляют прогениторы олигодендроцитов (ОП), осуществляющие миелинизацию аксонов в зрелом мозге на последних этапах дифференцировки. Цель обзора:  обобщить данные современных исследований, касающихся нарушений клеточного цикла семейства ОЛ при шизофрении и их возможных причин. Материалы и методы:  по ключевым словам «шизофрения, ОЛ, ОП», «ОП и гены риска шизофрении», «ОП и нейровоспаление», «ОП и антипсихотические препараты», «ОП, дофамин, серотонин» проведен поиск научных публикаций в базах MedLine/PubMed, Google Scholar, eLibrary. Для настоящего обзора отобрано 164 статьи, касающиеся связи перечисленных факторов с нарушениями дифференцировки ОП. Заключение:  для аутопсийного мозга пациентов характерен дефицит всех клеток семейства ОЛ, а также изменения корреляционных взаимосвязей между числом этих клеток, что может свидетельствовать о нарушениях дифференцировки ОП. Олигодендроцит- и миелин-связанные гены повышенного риска шизофрении играют значимую роль в регуляции дифференцировки ОП. В условиях нейровоспаления — важной составляющей патогенеза шизофрении — провоспалительные цитокины и активированная микроглия способны существенно влиять на пролиферацию и дифференцировку ОП. Атипичные нейролептики могут корректировать нарушения клеточного цикла семейства ОЛ и влиять на выраженность воспалительного процесса в мозге. Известно, что как ОЛ и ОП, так и микроглия и периферические иммунные клетки экспрессируют рецепторы дофамина и серотонина, основных мишеней этих препаратов. Патология ОП, тесно связанная с другими механизмами в патогенезе при шизофрении, рассматривается в качестве перспективной мишени для разработки новых подходов к фармакотерапии заболевания.

Background:  schizophrenia is considered as a dysconnectivity disorder supported by neuroimaging studies have revealed altered myelination of white and grey matter. Altered myelination suggests oligodendrocyte (OL) family pathology. Oligodendrocyte progenitors (OP) are of special interest since they myelinate axons in mature brain at the last stage of the differentiation. The aim of review  —  to summarize modern research data concerning altered cell cycle of OL family in schizophrenia and their plausible reason. Material and methods: using the keywords “schizophrenia, OL, OP”, “OP and schizophrenia risk genes”, “OP and neuroinflamation”, “OP and antipsychotic drugs”, “OP, dopamine, serotonin” 164 studies concerning the influence of listed above factors on OP differentiation were selected the MedLine/PubMed, Google Scholar, eLibrary databases for analysis.  Conclusion: postmortem studies demonstrated essential deficit of OL family cells as well as altered correlation pattern between the number of these cells suggested altered OP differentiation. Some of OL and myelin-related gene variants caused higher schizophrenia risk play a critical role in OP differentiation. While neuroinflammation is important component of schizophrenia brain pathology proinflammatory cytokines and activated microglia exert substantial influence on OP proliferation and differentiation. Atypical antipsychotics are able to correct OP maturation and have anti-inflammatory effects. OL and OP as well as microglia and peripheral immune cells express dopamine and serotonin receptors, main  therapeutic targets of these drugs. OP pathology as important component of schizophrenia  pathogenesis, tightly linked with another abnormalities, and considers as promising target for future therapeutic strategy.

шизофренияолигодендроцитыпрогениторы олигодендроцитовмиелин- и олигодендроцит-связанные гены риска шизофрениинейровоспалениеатипичные антипсихотические препаратынейромедиаторыschizophreniaoligodendrocyteoligodendrocyte progenitorsOL- and myelin-related risk genesneuroinflamationatypical antipsychoticsneurotransmittersReferencesSchmitt A, Hasan A, Gruber O, Falkai P. Schizophrenia as a disorder of disconnectivity. Eur Arch Psychiatry Clin Neurosci. 2011;261(2):150–154. doi: 10.1007/s00406-011-0242-2Schmitt A, Hasan A, Gruber O, Falkai P. Schizophrenia as a disorder of disconnectivity. Eur Arch Psychiatry Clin Neurosci. 2011;261(2):150–154. doi: 10.1007/s00406-011-0242-2Koshiyama D, Fukunaga M, Okada N, Morita K, Nemoto K, Usui K, Yamamori H, Yasuda Y, Fujimoto M, Kudo N, Azechi H, Watanabe Y, Hashimoto N, Narita H, Kusumi I, Ohi K, Shimada T, Kataoka Y, Yamamoto M, Ozaki N, Okada G, Okamoto Y, Harada K, Matsuo K, Yamasue H, Abe O, Hashimoto R, Takahashi T, Hori T, Nakataki M, Onitsuka T, Holleran L, Jahanshad N, van Erp TGM, Turner J, Donohoe G, Thompson PM, Kasai K, Hashimoto R; COCORO. White matter microstructural alterations across four major psychiatric disorders: megaanalysis study in 2937 individuals. Mol Psychiatry . 2020;25(4):883–895. doi: 10.1038/s41380-019-0553-7 Epub 2019 Nov 29. PMID: 31780770; PMCID: PMC7156346.Koshiyama D, Fukunaga M, Okada N, Morita K, Nemoto K, Usui K, Yamamori H, Yasuda Y, Fujimoto M, Kudo N, Azechi H, Watanabe Y, Hashimoto N, Narita H, Kusumi I, Ohi K, Shimada T, Kataoka Y, Yamamoto M, Ozaki N, Okada G, Okamoto Y, Harada K, Matsuo K, Yamasue H, Abe O, Hashimoto R, Takahashi T, Hori T, Nakataki M, Onitsuka T, Holleran L, Jahanshad N, van Erp TGM, Turner J, Donohoe G, Thompson PM, Kasai K, Hashimoto R; COCORO. White matter microstructural alterations across four major psychiatric disorders: megaanalysis study in 2937 individuals. Mol Psychiatry . 2020;25(4):883–895. doi: 10.1038/s41380-019-0553-7 Epub 2019 Nov 29. PMID: 31780770; PMCID: PMC7156346.Bells S, Lefebvre J, Longoni G, Narayanan S, Arnold DL, Yeh EA, Mabbott DJ. White matter plasticity and maturation in human cognition. Glia. 2019;67(11):2020– 2037. doi: 10.1002/glia.23661Bells S, Lefebvre J, Longoni G, Narayanan S, Arnold DL, Yeh EA, Mabbott DJ. White matter plasticity and maturation in human cognition. Glia. 2019;67(11):2020– 2037. doi: 10.1002/glia.23661Fields RD, Araque A, Johansen-Berg H, Lim SS, Lynch G, Nave KA, Nedergaard M, Perez R, Sejnowski T, Wake H. Glial biology in learning and cognition. Neuroscientist. 2014;20(5):426–431. doi: 10.1177/1073858413504465 Epub 2013 Oct 11. PMID: 24122821; PMCID: PMC4161624.Fields RD, Araque A, Johansen-Berg H, Lim SS, Lynch G, Nave KA, Nedergaard M, Perez R, Sejnowski T, Wake H. Glial biology in learning and cognition. Neuroscientist. 2014;20(5):426–431. doi: 10.1177/1073858413504465 Epub 2013 Oct 11. PMID: 24122821; PMCID: PMC4161624.Bartzokis G. Neuroglialpharmacology: myelination as a shared mechanism of action of psychotropic treatments. Neuropharmacology . 2012;62(7):2137–2153. doi: 10.1016/j.neuropharm.2012.01.015Bartzokis G. Neuroglialpharmacology: myelination as a shared mechanism of action of psychotropic treatments. Neuropharmacology . 2012;62(7):2137–2153. doi: 10.1016/j.neuropharm.2012.01.015Huntenburg JM, Bazin PL, Goulas A, Tardif CL, Villringer A, Margulies DS. A Systematic Relationship Between Functional Connectivity and Intracortical Myelin in the Human Cerebral Cortex. Cereb Cortex. 2017;27(2):981–997. doi: 10.1093/cercor/bhx030Huntenburg JM, Bazin PL, Goulas A, Tardif CL, Villringer A, Margulies DS. A Systematic Relationship Between Functional Connectivity and Intracortical Myelin in the Human Cerebral Cortex. Cereb Cortex. 2017;27(2):981–997. doi: 10.1093/cercor/bhx030Forkel SJ, Friedrich P, Thiebaut de Schotten M, Howells H. White matter variability, cognition, and disorders: a systematic review. Brain Struct Funct. 2022;227(2):529–544. doi: 10.1007/s00429-021-02382-wForkel SJ, Friedrich P, Thiebaut de Schotten M, Howells H. White matter variability, cognition, and disorders: a systematic review. Brain Struct Funct. 2022;227(2):529–544. doi: 10.1007/s00429-021-02382-wSakurai T, Gamo NJ, Hikida T, Kim SH, Murai T, Tomoda T, Sawa A. Converging models of schizophrenia — Network alterations of prefrontal cortex underlying cognitive impairments. Prog Neurobiol . 2015;134:178– 201. doi: 10.1016/j.pneurobio.2015.09.010Sakurai T, Gamo NJ, Hikida T, Kim SH, Murai T, Tomoda T, Sawa A. Converging models of schizophrenia — Network alterations of prefrontal cortex underlying cognitive impairments. Prog Neurobiol . 2015;134:178– 201. doi: 10.1016/j.pneurobio.2015.09.010Whitfield-Gabrieli S, Ford JM. Default mode network activity and connectivity in psychopathology. Annu Rev Clin Psychol . 2012;8:49–76. doi: 10.1146/an-nurev-clinpsy-032511-143049Whitfield-Gabrieli S, Ford JM. Default mode network activity and connectivity in psychopathology. Annu Rev Clin Psychol . 2012;8:49–76. doi: 10.1146/an-nurev-clinpsy-032511-143049Suminaite D, Lyons DA, Livesey MR. Myelinated axon physiology and regulation of neural circuit function. Glia . 2019;67(11):2050–2062. doi: 10.1002/glia.23665Suminaite D, Lyons DA, Livesey MR. Myelinated axon physiology and regulation of neural circuit function. Glia . 2019;67(11):2050–2062. doi: 10.1002/glia.23665Takahashi N, Sakurai T, Davis KL, Buxbaum JD. Linking oligodendrocyte and myelin dysfunction to neurocircuitry abnormalities in schizophrenia. Prog Neurobiol. 2011;93(1):13–24. doi: 10.1016/j.pneuro-bio.2010.09.004Takahashi N, Sakurai T, Davis KL, Buxbaum JD. Linking oligodendrocyte and myelin dysfunction to neurocircuitry abnormalities in schizophrenia. Prog Neurobiol. 2011;93(1):13–24. doi: 10.1016/j.pneuro-bio.2010.09.004Stephan KE, Friston KJ, Frith CD. Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring. Schizophr Bull. 2009;35(3):509–527. doi: 10.1093/schbul/sbn176Stephan KE, Friston KJ, Frith CD. Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring. Schizophr Bull. 2009;35(3):509–527. doi: 10.1093/schbul/sbn176Tanaka H, Ma J, Tanaka KF, Takao K, Komada M, Tanda K, Suzuki A, Ishibashi T, Baba H, Isa T, Shigemoto R, Ono K, Miyakawa T, Ikenaka K. Mice with altered myelin proteolipid protein gene expression display cognitive deficits accompanied by abnormal neuronglia interactions and decreased conduction velocities. J Neurosci. 2009;29(26):8363–8371. doi: 10.1523/JNEUROSCI.3216-08.2009Tanaka H, Ma J, Tanaka KF, Takao K, Komada M, Tanda K, Suzuki A, Ishibashi T, Baba H, Isa T, Shigemoto R, Ono K, Miyakawa T, Ikenaka K. Mice with altered myelin proteolipid protein gene expression display cognitive deficits accompanied by abnormal neuronglia interactions and decreased conduction velocities. J Neurosci. 2009;29(26):8363–8371. doi: 10.1523/JNEUROSCI.3216-08.2009Dawson MR, Polito A, Levine JM, Reynolds R. NG2-expressing glial progenitor cells: an abundant and widespread population of cycling cells in the adult rat CNS. Mol Cell Neurosci. 2003;24(2):476–488. doi: 10.1016/s1044-7431(03)00210-0Dawson MR, Polito A, Levine JM, Reynolds R. NG2-expressing glial progenitor cells: an abundant and widespread population of cycling cells in the adult rat CNS. Mol Cell Neurosci. 2003;24(2):476–488. doi: 10.1016/s1044-7431(03)00210-0Fekete CD, Nishiyama A. Presentation and integration of multiple signals that modulate oligodendrocyte lineage progression and myelination. Front Cell Neurosci. 2022;16:1041853. doi: 10.3389/fn-cel.2022.1041853Fekete CD, Nishiyama A. Presentation and integration of multiple signals that modulate oligodendrocyte lineage progression and myelination. Front Cell Neurosci. 2022;16:1041853. doi: 10.3389/fn-cel.2022.1041853Zhu X , Hill RA, Dietr ich D, Komitova M, Suzuki R, Nishiyama A. Age-dependent fate and lineage restriction of single NG2 cells. Development. 2011;138(4):745– 753. doi: 10.1242/dev.047951Zhu X , Hill RA, Dietr ich D, Komitova M, Suzuki R, Nishiyama A. Age-dependent fate and lineage restriction of single NG2 cells. Development. 2011;138(4):745– 753. doi: 10.1242/dev.047951Kang SH, Fukaya M, Yang JK, Rothstein JD, Bergles DE. NG2 + CNS glial progenitors remain committed to the oligodendrocyte lineage in post-natal life and following neurodegeneration. Neuron . 2010;68(4):668–681. doi: 10.1016/j.neuron.2010.09.009Kang SH, Fukaya M, Yang JK, Rothstein JD, Bergles DE. NG2 + CNS glial progenitors remain committed to the oligodendrocyte lineage in post-natal life and following neurodegeneration. Neuron . 2010;68(4):668–681. doi: 10.1016/j.neuron.2010.09.009Bergles DE, Richardson WD. Oligodendrocyte Development and Plasticity. Cold Spring Harb Perspect Biol . 2015;8(2):a020453. doi: 10.1101/cshperspect.a020453Bergles DE, Richardson WD. Oligodendrocyte Development and Plasticity. Cold Spring Harb Perspect Biol . 2015;8(2):a020453. doi: 10.1101/cshperspect.a020453Nagy B, Hovhannisyan A, Barzan R, Chen TJ, Kukley M. Different patterns of neuronal activity trigger distinct responses of oligodendrocyte precursor cells in the corpus callosum. PLoS Biol. 2017;15(8):e2001993. doi: 10.1371/journal.pbio.2001993Nagy B, Hovhannisyan A, Barzan R, Chen TJ, Kukley M. Different patterns of neuronal activity trigger distinct responses of oligodendrocyte precursor cells in the corpus callosum. PLoS Biol. 2017;15(8):e2001993. doi: 10.1371/journal.pbio.2001993Mitew S, Gobius I, Fenlon LR, McDougall SJ, Hawkes D, Xing YL, Bujalka H, Gundlach AL, Richards LJ, Kilpatrick TJ, Merson TD, Emery B. Pharmacogenetic stimulation of neuronal activity increases myelination in an axon-specific manner. Nat Commun . 2018;9(1):306. doi: 10.1038/s41467-017-02719-2Mitew S, Gobius I, Fenlon LR, McDougall SJ, Hawkes D, Xing YL, Bujalka H, Gundlach AL, Richards LJ, Kilpatrick TJ, Merson TD, Emery B. Pharmacogenetic stimulation of neuronal activity increases myelination in an axon-specific manner. Nat Commun . 2018;9(1):306. doi: 10.1038/s41467-017-02719-2Linneberg C, Toft CLF, Kjaer-Sorensen K, Laurs-en LS. L1cam-mediated developmental processes of the nervous system are differentially regulated by proteolytic processing. Sci Rep . 2019;9(1):3716. doi: 10.1038/s41598-019-39884-xLinneberg C, Toft CLF, Kjaer-Sorensen K, Laurs-en LS. L1cam-mediated developmental processes of the nervous system are differentially regulated by proteolytic processing. Sci Rep . 2019;9(1):3716. doi: 10.1038/s41598-019-39884-xClayton BLJ, Paul J. Tesar PJ. Oligodendrocyte progenitor cell fate and function in development and disease. Curr Opin Cell Biol . 2021;73:35–40. doi: 10.1016/j.ceb.2021.05.003Clayton BLJ, Paul J. Tesar PJ. Oligodendrocyte progenitor cell fate and function in development and disease. Curr Opin Cell Biol . 2021;73:35–40. doi: 10.1016/j.ceb.2021.05.003Uranova NA, Vikhreva OV, Rakhmanova VI, Orlovskaya DD. Ultrastructural pathology of oligodendrocytes adjacent to microglia in prefrontal white matter in schizophrenia. NPJ Schizophr. 2018;4(1):26. doi: 10.1038/s41537-018-0068-2Uranova NA, Vikhreva OV, Rakhmanova VI, Orlovskaya DD. Ultrastructural pathology of oligodendrocytes adjacent to microglia in prefrontal white matter in schizophrenia. NPJ Schizophr. 2018;4(1):26. doi: 10.1038/s41537-018-0068-2Vikhreva OV, Rakhmanova VI, Orlovskaya DD, Uranova NA. Ultrastructural alterations of oligodendrocytes in prefrontal white matter in schizophrenia: A post-mortem morphometric study. Schizophr Res. 2016;177(1–3):28–36. doi: 10.1016/j.schres.2016.04.023Vikhreva OV, Rakhmanova VI, Orlovskaya DD, Uranova NA. Ultrastructural alterations of oligodendrocytes in prefrontal white matter in schizophrenia: A post-mortem morphometric study. Schizophr Res. 2016;177(1–3):28–36. doi: 10.1016/j.schres.2016.04.023Uranova NA, Vikhreva OV, Rachmanova VI, Orlovskaya DD. Ultrastructural alterations of myelinated fibers and oligodendrocytes in the prefrontal cortex in schizophrenia: a postmortem morphometric study. Schizophr Res Treatment . 2011;2011:325789. doi: 10.1155/2011/325789Uranova NA, Vikhreva OV, Rachmanova VI, Orlovskaya DD. Ultrastructural alterations of myelinated fibers and oligodendrocytes in the prefrontal cortex in schizophrenia: a postmortem morphometric study. Schizophr Res Treatment . 2011;2011:325789. doi: 10.1155/2011/325789Schmitt A, Tatsch L, Vollhardt A, Schneider-Axmann T, Raabe FJ, Roell L, Heinsen H, Hof PR, Falkai P, Schmitz C. Decreased Oligodendrocyte Number in Hippocampal Subfield CA4 in Schizophrenia: A Replication Study. Cells. 2022;11(20):3242. doi: 10.3390/cells11203242Schmitt A, Tatsch L, Vollhardt A, Schneider-Axmann T, Raabe FJ, Roell L, Heinsen H, Hof PR, Falkai P, Schmitz C. Decreased Oligodendrocyte Number in Hippocampal Subfield CA4 in Schizophrenia: A Replication Study. Cells. 2022;11(20):3242. doi: 10.3390/cells11203242Falkai P, Raabe F, Bogerts B, Schneider-Axmann T, Malchow B, Tatsch L, Huber V, Slapakova L, Dobrowolny H, Schmitz C, Cantuti-Castelvetri L, Simons M, Steiner J, Schmitt A. Association between altered hippocampal oligodendrocyte number and neuronal circuit structures in schizophrenia: a post-mortem analysis. Eur Arch Psychiatry Clin Neurosci. 2020;270(4):413–424. doi: 10.1007/s00406-019-01067-0Falkai P, Raabe F, Bogerts B, Schneider-Axmann T, Malchow B, Tatsch L, Huber V, Slapakova L, Dobrowolny H, Schmitz C, Cantuti-Castelvetri L, Simons M, Steiner J, Schmitt A. Association between altered hippocampal oligodendrocyte number and neuronal circuit structures in schizophrenia: a post-mortem analysis. Eur Arch Psychiatry Clin Neurosci. 2020;270(4):413–424. doi: 10.1007/s00406-019-01067-0Falkai P, Steiner J, Malchow B, Shariati J, Knaus A, Bernstein HG, Schneider-Axmann T, Kraus T, Hasan A, Bogerts B, Schmitt A. Oligodendrocyte and Interneuron Density in Hippocampal Subfields in Schizophrenia and Association of Oligodendrocyte Number with Cognitive Deficits. Front Cell Neurosci . 2016;10:78. doi: 10.3389/fncel.2016.00078Falkai P, Steiner J, Malchow B, Shariati J, Knaus A, Bernstein HG, Schneider-Axmann T, Kraus T, Hasan A, Bogerts B, Schmitt A. Oligodendrocyte and Interneuron Density in Hippocampal Subfields in Schizophrenia and Association of Oligodendrocyte Number with Cognitive Deficits. Front Cell Neurosci . 2016;10:78. doi: 10.3389/fncel.2016.00078Востриков ВМ, Уранова НА, Рахманова ВИ, Орловская ДД. Сниженная численная плотность олигодендроглиоцитов в префронтальной коре при шизофрении. Журнал неврологии и психиатрии имени С.С. Корсакова. 2004;104(1):47–51.Vostrikov VM, Uranova NA, Rakhmanova VI, Orlovskaia DD. Lowered oligodendroglial cell density inthe prefrontal cortex in schizophrenia. Zhurnal Nevrologii i Psihiatrii imeni S.S. Korsakova. 2004;104(1):47–51. (In Russ.).Segal D, Schmitz C, Hof PR. Spatial distribution and density of oligodendrocytes in the cingulum bundle are unaltered in schizophrenia. Acta Neuropathol. 2009;117(4):385–394. doi: 10.1007/s00401-008-0379-xSegal D, Schmitz C, Hof PR. Spatial distribution and density of oligodendrocytes in the cingulum bundle are unaltered in schizophrenia. Acta Neuropathol. 2009;117(4):385–394. doi: 10.1007/s00401-008-0379-xSzuchet S, Nielsen JA, Lovas G, Domowicz MS, de Velasco JM, Maric D, Hudson LD. The genetic signature of perineuronal oligodendrocytes reveals their unique phenotype. Eur J Neurosci. 2011;34(12):1906–1922. doi: 10.1111/j.1460-9568.2011.07922.xSzuchet S, Nielsen JA, Lovas G, Domowicz MS, de Velasco JM, Maric D, Hudson LD. The genetic signature of perineuronal oligodendrocytes reveals their unique phenotype. Eur J Neurosci. 2011;34(12):1906–1922. doi: 10.1111/j.1460-9568.2011.07922.xBattefeld A, Klooster J, Kole MH. Myelinating satellite oligodendrocytes are integrated in a glial syncytium constraining neuronal high-frequency activity. Nat Commun. 2016;7:11298. doi: 10.1038/ncomms11298Battefeld A, Klooster J, Kole MH. Myelinating satellite oligodendrocytes are integrated in a glial syncytium constraining neuronal high-frequency activity. Nat Commun. 2016;7:11298. doi: 10.1038/ncomms11298Kolomeets NS, Uranova NA. Reduced oligodendrocyte density in layer 5 of the prefrontal cortex in schizophrenia. Eur Arch Psychiatry Clin Neurosci . 2018;23:1– 8. doi: 10.1007/s00406-018-0888-0Kolomeets NS, Uranova NA. Reduced oligodendrocyte density in layer 5 of the prefrontal cortex in schizophrenia. Eur Arch Psychiatry Clin Neurosci . 2018;23:1– 8. doi: 10.1007/s00406-018-0888-0Коломеец НС, Востриков ВМ. Нарушения кластеризации олигодендроцитов в супра- и инфрагранулярных слоях поля 10 префронтальной коры при шизофрении. Журнал неврологии и психиатрии имени С.С. Корсакова . 2019;119(12):62–68. doi: 10.17116/jnevro201911912162Kolomeets NS, Vostrikov VM. Abnormalities of oligodendrocyte clusters in supra- and infragranular layers of the prefrontal cortex in schizophrenia S.S. Korsakov Journal of Neurology and Psychiatry/ Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2019;119(12):62–68. (In Russ.). doi: 10.17116/jnev-ro201911912162Kolomeets NS, Uranova NA. Reduced number of satellite oligodendrocytes of pyramidal neurons in layer 5 of the prefrontal cortex in schizophrenia. Eur Arch Psychiatry Clin Neurosci . 2021;272(6):947–955. doi: 10.1007/s00406-021-01353-wKolomeets NS, Uranova NA. Reduced number of satellite oligodendrocytes of pyramidal neurons in layer 5 of the prefrontal cortex in schizophrenia. Eur Arch Psychiatry Clin Neurosci . 2021;272(6):947–955. doi: 10.1007/s00406-021-01353-wKolomeets NS, Vostrikov VM, Uranova NA. Abnormalities in oligodendrocyte clusters in the inferior parietal cortex in schizophrenia are associated with insight. Eur J Psychiat . 2013;27(4):24 8–258. doi: 10.4321/S0213-61632013000400003Kolomeets NS, Vostrikov VM, Uranova NA. Abnormalities in oligodendrocyte clusters in the inferior parietal cortex in schizophrenia are associated with insight. Eur J Psychiat . 2013;27(4):24 8–258. doi: 10.4321/S0213-61632013000400003Uranova NA, Vostrikov VM, Kolomeets NS. Oligodendrocyte abnormalities in layer 5 in the inferior parietal lobule are associated with lack of insight: a postmortem morphometric study. Eur J Psychiat. 2015;29(3):215–222. doi: 10.4321/S0213-61632015000300006Uranova NA, Vostrikov VM, Kolomeets NS. Oligodendrocyte abnormalities in layer 5 in the inferior parietal lobule are associated with lack of insight: a postmortem morphometric study. Eur J Psychiat. 2015;29(3):215–222. doi: 10.4321/S0213-61632015000300006Vostrikov VM, Kolomeets NS, Uranova NA. Deficit of perineuronal oligodendrocytes in the inferior parietal lobule is associated with lack of insight in schizophrenia. Eur J Psychiat . 2014;28(2):114–123. doi: 10.4321/S0213-61632014000200005Vostrikov VM, Kolomeets NS, Uranova NA. Deficit of perineuronal oligodendrocytes in the inferior parietal lobule is associated with lack of insight in schizophrenia. Eur J Psychiat . 2014;28(2):114–123. doi: 10.4321/S0213-61632014000200005van den Heuvel MP, Fornito A. Brain networks in schizophrenia . Neuropsychol Rev . 2014;24(1):32–48. doi: 10.1007/s11065-014-9248-7van den Heuvel MP, Fornito A. Brain networks in schizophrenia . Neuropsychol Rev . 2014;24(1):32–48. doi: 10.1007/s11065-014-9248-7Chahine G, Richter A, Wolter S, Goya-Maldonado R, Gruber O. Disruptions in the left frontoparietal network underlie resting state endophenotypic markers in schizophrenia. Hum Brain Mapp. 2017;38(4):1741– 1750. doi: 10.1002/hbm.23477Chahine G, Richter A, Wolter S, Goya-Maldonado R, Gruber O. Disruptions in the left frontoparietal network underlie resting state endophenotypic markers in schizophrenia. Hum Brain Mapp. 2017;38(4):1741– 1750. doi: 10.1002/hbm.23477Liu X, Zhuo C, Qin W, Zhu J, Xu L, Xu Y, Yu C. Selective functional connectivity abnormality of the transition zone of the inferior parietal lobule in schizophrenia. Neuroimage Clin . 2016;11:789–795. doi: 10.1016/j.nicl.2016.05.021Liu X, Zhuo C, Qin W, Zhu J, Xu L, Xu Y, Yu C. Selective functional connectivity abnormality of the transition zone of the inferior parietal lobule in schizophrenia. Neuroimage Clin . 2016;11:789–795. doi: 10.1016/j.nicl.2016.05.021Wei W, Zhang Y, Li Y, Meng Y, Li M, Wang Q, Deng W, Ma X, Palaniyappan L, Zhang N, Li T. Depth-dependent abnormal cortical myelination in first-episode treatment-naïve schizophrenia. Hum Brain Mapp. 2020;41(10):2782–2793. doi: 10.1002/hbm.24977Wei W, Zhang Y, Li Y, Meng Y, Li M, Wang Q, Deng W, Ma X, Palaniyappan L, Zhang N, Li T. Depth-dependent abnormal cortical myelination in first-episode treatment-naïve schizophrenia. Hum Brain Mapp. 2020;41(10):2782–2793. doi: 10.1002/hbm.24977Vartanian O, Beatty EL, Smith I, Blackler K, Lam Q, Forbes S. One-way traffic: The inferior frontal gyrus controls brain activation in the middle temporal gyrus and inferior parietal lobule during divergent thinking. Neuropsychologia. 2018;118:68–78. doi: 10.1016/j.neuropsychologia.2018.02.024Vartanian O, Beatty EL, Smith I, Blackler K, Lam Q, Forbes S. One-way traffic: The inferior frontal gyrus controls brain activation in the middle temporal gyrus and inferior parietal lobule during divergent thinking. Neuropsychologia. 2018;118:68–78. doi: 10.1016/j.neuropsychologia.2018.02.024Price CJ. The anatomy of language: contributions from functional neuroimaging. J Anat. 2000;197 Pt 3(Pt 3):335–359. doi: 10.1046/j.1469-7580.2000.19730335.xPrice CJ. The anatomy of language: contributions from functional neuroimaging. J Anat. 2000;197 Pt 3(Pt 3):335–359. doi: 10.1046/j.1469-7580.2000.19730335.xCunningham SI, Tomasi D, Volkow ND. Structural and functional connectivity of the precuneus and thalamus to the default mode network. Hum Brain Mapp. 2017;38(2):938–956. doi: 10.1002/hbm.23429Cunningham SI, Tomasi D, Volkow ND. Structural and functional connectivity of the precuneus and thalamus to the default mode network. Hum Brain Mapp. 2017;38(2):938–956. doi: 10.1002/hbm.23429Humphreys GF, Lambon Ralph MA. Fusion and Fission of Cognitive Functions in the Human Parietal Cortex. Cereb Cortex . 2015;25(10):3547–3560. doi: 10.1093/cercor/bhu198Humphreys GF, Lambon Ralph MA. Fusion and Fission of Cognitive Functions in the Human Parietal Cortex. Cereb Cortex . 2015;25(10):3547–3560. doi: 10.1093/cercor/bhu198van Kemenade BM, Arikan BE, Kircher T, Straube B. The angular gyrus is a supramodal comparator area in action-outcome monitoring. Brain Struct Funct. 2017;222(8):3691–3703. doi: 10.1007/s00429-017-1428-9van Kemenade BM, Arikan BE, Kircher T, Straube B. The angular gyrus is a supramodal comparator area in action-outcome monitoring. Brain Struct Funct. 2017;222(8):3691–3703. doi: 10.1007/s00429-017-1428-9Hilgetag CC, Grant S. Uniformity, specificity and variability of corticocortical connectivity. Philos Trans R Soc Lond B Biol Sci . 2000;355(1393):7–20. doi: 10.1098/rstb.2000.0546Hilgetag CC, Grant S. Uniformity, specificity and variability of corticocortical connectivity. Philos Trans R Soc Lond B Biol Sci . 2000;355(1393):7–20. doi: 10.1098/rstb.2000.0546Theyel BB, Llano DA, Sherman SM. The corticothal-amocortical circuit drives higher-order cortex in the mouse. Nat Neurosci . 2010;13(1):84–88. doi: 10.1038/nn.2449Theyel BB, Llano DA, Sherman SM. The corticothal-amocortical circuit drives higher-order cortex in the mouse. Nat Neurosci . 2010;13(1):84–88. doi: 10.1038/nn.2449Sherman SM, Guillery RW. Distinct functions for direct and transthalamic corticocortical connections. J Neurophysiol. 2011;106(3):1068–1077. doi: 10.1152/jn.00429.2011 Epub 2011 Jun 15. PMID: 21676936.Sherman SM, Guillery RW. Distinct functions for direct and transthalamic corticocortical connections. J Neurophysiol. 2011;106(3):1068–1077. doi: 10.1152/jn.00429.2011 Epub 2011 Jun 15. PMID: 21676936.Micheva KD, Wolman D, Mensh BD, Pax E, Buchanan J, Smith SJ, Bock DD. A large fraction of neocortical myelin ensheathes axons of local inhibitory neurons. Elife. 2016;5:e15784. doi: 10.7554/eLife.15784Micheva KD, Wolman D, Mensh BD, Pax E, Buchanan J, Smith SJ, Bock DD. A large fraction of neocortical myelin ensheathes axons of local inhibitory neurons. Elife. 2016;5:e15784. doi: 10.7554/eLife.15784Yao B, Neggers SFW, Kahn RS, Thakkar KN. Altered thalamocortical structural connectivity in persons with schizophrenia and healthy siblings. Neuroimage Clin. 2020;28:102370. doi: 10.1016/j.nicl.2020.102370Yao B, Neggers SFW, Kahn RS, Thakkar KN. Altered thalamocortical structural connectivity in persons with schizophrenia and healthy siblings. Neuroimage Clin. 2020;28:102370. doi: 10.1016/j.nicl.2020.102370Roussos P, Haroutunian V. Schizophrenia: susceptibility genes and oligodendroglial and myelin related abnormalities. Front Cell Neurosci . 2014;8:5. doi: 10.3389/fncel.2014.00005Roussos P, Haroutunian V. Schizophrenia: susceptibility genes and oligodendroglial and myelin related abnormalities. Front Cell Neurosci . 2014;8:5. doi: 10.3389/fncel.2014.00005Georgieva L, Moskvina V, Peirce T, Norton N, Bray NJ, Jones L, Holmans P, Macgregor S, Zammit S, Wilkinson J, Williams H, Nikolov I, Williams N, Ivanov D, Davis KL, Haroutunian V, Buxbaum JD, Craddock N, Kirov G, Owen MJ, O’Donovan MC. Convergent evidence that oligodendrocyte lineage transcription factor 2 (OLIG2) and interacting genes influence susceptibility to schizophrenia. Proc Natl Acad Sci USA. 2006;103(33):12469–12474. doi: 10.1073/pnas.0603029103Georgieva L, Moskvina V, Peirce T, Norton N, Bray NJ, Jones L, Holmans P, Macgregor S, Zammit S, Wilkinson J, Williams H, Nikolov I, Williams N, Ivanov D, Davis KL, Haroutunian V, Buxbaum JD, Craddock N, Kirov G, Owen MJ, O’Donovan MC. Convergent evidence that oligodendrocyte lineage transcription factor 2 (OLIG2) and interacting genes influence susceptibility to schizophrenia. Proc Natl Acad Sci USA. 2006;103(33):12469–12474. doi: 10.1073/pnas.0603029103Komatsu H, Takeuchi H, Kikuchi Y, Ono C, Yu Z, Iizuka K, Takano Y, Kakuto Y, Funakoshi S, Ono T, Ito J, Kunii Y, Hino M, Nagaoka A, Iwasaki Y, Yamamori H, Yasuda Y, Fujimoto M, Azechi H, Kudo N, Hashimoto R, Yabe H, Yoshida M, Saito Y, Kakita A, Fuse N, Kawashima R, Taki Y, Tomita H. Ethnicity-Dependent Effects of Schizophrenia Risk Variants of the OLIG2 Gene on OLIG2 Transcription and White Matter Integrity. Schizophr Bull . 2020;46(6):1619–1628. doi: 10.1093/schbul/sbaa049Komatsu H, Takeuchi H, Kikuchi Y, Ono C, Yu Z, Iizuka K, Takano Y, Kakuto Y, Funakoshi S, Ono T, Ito J, Kunii Y, Hino M, Nagaoka A, Iwasaki Y, Yamamori H, Yasuda Y, Fujimoto M, Azechi H, Kudo N, Hashimoto R, Yabe H, Yoshida M, Saito Y, Kakita A, Fuse N, Kawashima R, Taki Y, Tomita H. Ethnicity-Dependent Effects of Schizophrenia Risk Variants of the OLIG2 Gene on OLIG2 Transcription and White Matter Integrity. Schizophr Bull . 2020;46(6):1619–1628. doi: 10.1093/schbul/sbaa049Chubb JE, Bradshaw NJ, Soares DC, Porteous DJ, Millar JK. The DISC locus in psychiatric illness. Mol Psychiatry. 2008;13(1):36–64. doi: 10.1038/sj.mp.4002106Chubb JE, Bradshaw NJ, Soares DC, Porteous DJ, Millar JK. The DISC locus in psychiatric illness. Mol Psychiatry. 2008;13(1):36–64. doi: 10.1038/sj.mp.4002106Hattori T, Shimizu S, Koyama Y, Emoto H, Matsumoto Y, Kumamoto N, Yamada K, Takamura H, Matsuzaki S, Katayama T, Tohyama M, Ito A. DISC1 (disrupted-in-schizophrenia-1) regulates differentiation of oligodendrocytes. PLoS One. 2014;9(2):e88506. doi: 10.1371/journal.pone.0088506Hattori T, Shimizu S, Koyama Y, Emoto H, Matsumoto Y, Kumamoto N, Yamada K, Takamura H, Matsuzaki S, Katayama T, Tohyama M, Ito A. DISC1 (disrupted-in-schizophrenia-1) regulates differentiation of oligodendrocytes. PLoS One. 2014;9(2):e88506. doi: 10.1371/journal.pone.0088506Bernstein HG, Jauch E, Dobrowolny H, Mawrin C, Steiner J, Bogerts B. Increased density of DISC1-immunoreactive oligodendroglial cells in fronto-parietal white matter of patients with paranoid schizophrenia. Eur Arch Psychiatry Clin Neurosci . 2016;266(6):495–504. doi: 10.1007/s00406-015-0640-y Epub 2015 Aug 28. PMID: 26315603.Bernstein HG, Jauch E, Dobrowolny H, Mawrin C, Steiner J, Bogerts B. Increased density of DISC1-immunoreactive oligodendroglial cells in fronto-parietal white matter of patients with paranoid schizophrenia. Eur Arch Psychiatry Clin Neurosci . 2016;266(6):495–504. doi: 10.1007/s00406-015-0640-y Epub 2015 Aug 28. PMID: 26315603.Millar JK. Disruption of two novel genes by a trans-location co-segregating with schizophrenia. Hum Mol Genet. 2000;9:1415–1423. doi: 10.1093/hmg/9.9.1415Millar JK. Disruption of two novel genes by a trans-location co-segregating with schizophrenia. Hum Mol Genet. 2000;9:1415–1423. doi: 10.1093/hmg/9.9.1415Yu G, Su Y, Guo C, Yi C, Yu B, Chen H, Cui Y, Wang X, Wang Y, Chen X, Wang S, Wang Q, Chen X, Hu X, Mei F, Verkhratsky A, Xiao L, Niu J. Pathological oligodendrocyte precursor cells revealed in human schizophrenic brains and trigger schizophrenia-like behaviors and synaptic defects in genetic animal model. Mol Psychiatry. 2022;27(12):5154–5166. doi: 10.1038/s41380-022-01777-3Yu G, Su Y, Guo C, Yi C, Yu B, Chen H, Cui Y, Wang X, Wang Y, Chen X, Wang S, Wang Q, Chen X, Hu X, Mei F, Verkhratsky A, Xiao L, Niu J. Pathological oligodendrocyte precursor cells revealed in human schizophrenic brains and trigger schizophrenia-like behaviors and synaptic defects in genetic animal model. Mol Psychiatry. 2022;27(12):5154–5166. doi: 10.1038/s41380-022-01777-3Shimizu S, Koyama Y, Hattori T, Tachibana T, Yoshimi T, Emoto H, Matsumoto Y, Miyata S, Katayama T, Ito A, Tohyama M. DBZ, a CNS-specific DISC1 binding protein, positively regulates oligodendrocyte differentiation. Glia. 2014;62(5):709–724. doi: 10.1002/glia.22636Shimizu S, Koyama Y, Hattori T, Tachibana T, Yoshimi T, Emoto H, Matsumoto Y, Miyata S, Katayama T, Ito A, Tohyama M. DBZ, a CNS-specific DISC1 binding protein, positively regulates oligodendrocyte differentiation. Glia. 2014;62(5):709–724. doi: 10.1002/glia.22636Yamamuro K, Kimoto S, Rosen KM, Kishimoto T, Makinodan M. Potential primary roles of glial cells in the mechanisms of psychiatric disorders. Front Cell Neurosci. 2015;9:154. doi: 10.3389/fncel.2015.00154Yamamuro K, Kimoto S, Rosen KM, Kishimoto T, Makinodan M. Potential primary roles of glial cells in the mechanisms of psychiatric disorders. Front Cell Neurosci. 2015;9:154. doi: 10.3389/fncel.2015.00154Anitha A, Nakamura K, Yamada K, Iwayama Y, Toyota T, Takei N, Iwata Y, Suzuki K, Sekine Y, Matsuzaki H, Kawai M, Thanseem I, Miyoshi K, Katayama T, Matsuzaki S, Baba K, Honda A, Hattori T, Shimizu S, Kumamoto N, Kikuchi M, Tohyama M, Yoshikawa T, Mori N. Association studies and gene expression analyses of the DISC1-interacting molecules, pericentrin 2 (PCNT2) and DISC1-binding zinc finger protein (DBZ), with schizophrenia and with bipolar disorder. Am J Med Genet B Neuropsychiatr Genet . 2009;150B(7):967–976. doi: 10.1002/ajmg.b.30926Anitha A, Nakamura K, Yamada K, Iwayama Y, Toyota T, Takei N, Iwata Y, Suzuki K, Sekine Y, Matsuzaki H, Kawai M, Thanseem I, Miyoshi K, Katayama T, Matsuzaki S, Baba K, Honda A, Hattori T, Shimizu S, Kumamoto N, Kikuchi M, Tohyama M, Yoshikawa T, Mori N. Association studies and gene expression analyses of the DISC1-interacting molecules, pericentrin 2 (PCNT2) and DISC1-binding zinc finger protein (DBZ), with schizophrenia and with bipolar disorder. Am J Med Genet B Neuropsychiatr Genet . 2009;150B(7):967–976. doi: 10.1002/ajmg.b.30926Nielsen JA, Hudson LD, Armstrong RC. Nuclear organization in differentiating oligodendrocytes. J Cell Sci. 2002;115:4071–4079. doi: 10.1242/jcs.00103Nielsen JA, Hudson LD, Armstrong RC. Nuclear organization in differentiating oligodendrocytes. J Cell Sci. 2002;115:4071–4079. doi: 10.1242/jcs.00103Li M, Xiao L, Chen X. Histone Acetylation and Methylation Underlie Oligodendroglial and Myelin Susceptibility in Schizophrenia. Front Cell Neurosci . 2022;16:823708. doi: 10.3389/fncel.2022.823708Li M, Xiao L, Chen X. Histone Acetylation and Methylation Underlie Oligodendroglial and Myelin Susceptibility in Schizophrenia. Front Cell Neurosci . 2022;16:823708. doi: 10.3389/fncel.2022.823708Chen X, Duan H, Xiao L, Gan J. Genetic and Epigenetic Alterations Underlie Oligodendroglia Susceptibility and White Matter Etiology in Psychiatric Disorders. Front Genet. 2018;9:565. doi: 10.3389/fgene.2018.00565Chen X, Duan H, Xiao L, Gan J. Genetic and Epigenetic Alterations Underlie Oligodendroglia Susceptibility and White Matter Etiology in Psychiatric Disorders. Front Genet. 2018;9:565. doi: 10.3389/fgene.2018.00565Solek CM, Farooqi N, Verly M, Lim TK, Ruthazer ES. Maternal immune activation in neurodevelopmental disorders. Developmental Dynamics . 2018;247(4):588– 619. doi: 10.1002/dvdy.24612Solek CM, Farooqi N, Verly M, Lim TK, Ruthazer ES. Maternal immune activation in neurodevelopmental disorders. Developmental Dynamics . 2018;247(4):588– 619. doi: 10.1002/dvdy.24612Smigielski L, Jagannath V, Rössler W, Walitza S, Grünblatt E. Epigenetic mechanisms in schizophrenia and other psychotic disorders: a systematic review of empirical human findings. Mol Psychiatry . 2020;25(8):1718–1748. doi: 10.1038/s41380-019-0601-3Smigielski L, Jagannath V, Rössler W, Walitza S, Grünblatt E. Epigenetic mechanisms in schizophrenia and other psychotic disorders: a systematic review of empirical human findings. Mol Psychiatry . 2020;25(8):1718–1748. doi: 10.1038/s41380-019-0601-3Lanz TA, Reinhart V, Sheehan MJ, Rizzo SJS, Bove SE, James LC, Volfson D, Lewis DA, Kleiman RJ. Postmortem transcriptional profiling reveals widespread increase in inflammation in schizophrenia: a comparison of prefrontal cor-tex, striatum, and hippocampus among matched tetrads of controls with subjects diagnosed with schizophrenia, bipolar or major depressive disor-der. Transl Psychiatr y . 2019;9(1):151. doi: 10.1038/s41398-019-0492-8Lanz TA, Reinhart V, Sheehan MJ, Rizzo SJS, Bove SE, James LC, Volfson D, Lewis DA, Kleiman RJ. Postmortem transcriptional profiling reveals widespread increase in inflammation in schizophrenia: a comparison of prefrontal cor-tex, striatum, and hippocampus among matched tetrads of controls with subjects diagnosed with schizophrenia, bipolar or major depressive disor-der. Transl Psychiatr y . 2019;9(1):151. doi: 10.1038/s41398-019-0492-8Momtazmanesh S, Zare-Shahabadi A, Rezaei N. Cy-tokine Alterations in Schizophrenia: An Updated Review. Front Psychiatry. 2019;10:892. doi: 10.3389/fpsyt.2019.00892Momtazmanesh S, Zare-Shahabadi A, Rezaei N. Cy-tokine Alterations in Schizophrenia: An Updated Review. Front Psychiatry. 2019;10:892. doi: 10.3389/fpsyt.2019.00892Müller N. Immunological aspects of the treatment of depression and schizophrenia. Dialogues Clin Neuros-ci . 2017;19(1):55–63. doi: 10.31887/DCNS.2017.19.1/nmuellerMüller N. Immunological aspects of the treatment of depression and schizophrenia. Dialogues Clin Neuros-ci . 2017;19(1):55–63. doi: 10.31887/DCNS.2017.19.1/nmuellerZhang Z, Li X, Zhou H, Zhou J. NG2-glia crosstalk with microglia in health and disease. CNS Neurosci Ther. 2022;28(11):1663–1674. doi: 10.1111/cns.13948Zhang Z, Li X, Zhou H, Zhou J. NG2-glia crosstalk with microglia in health and disease. CNS Neurosci Ther. 2022;28(11):1663–1674. doi: 10.1111/cns.13948Guo S, Wang H, Yin Y. Microglia Polarization From M1 to M2 in Neurodegenerative Diseases. Front Aging Neurosci. 2022;14:815347. doi: 10.3389/fnagi.2022.815347Guo S, Wang H, Yin Y. Microglia Polarization From M1 to M2 in Neurodegenerative Diseases. Front Aging Neurosci. 2022;14:815347. doi: 10.3389/fnagi.2022.815347Hughes EG, Kang SH, Fukaya M, Bergles DE. Oligodendrocyte progenitors balance growth with self-repulsion to achieve homeostasis in the adult brain. Nat Neurosci. 2013;16(6):668–676. doi: 10.1038/nn.3390Hughes EG, Kang SH, Fukaya M, Bergles DE. Oligodendrocyte progenitors balance growth with self-repulsion to achieve homeostasis in the adult brain. Nat Neurosci. 2013;16(6):668–676. doi: 10.1038/nn.3390Kuhn S, Gritti L, Crooks D, Dombrowski Y. Oligodendrocytes in Development, Myelin Generation and Beyond. Cells. 2019;8(11):1424. doi: 10.3390/cells8111424Kuhn S, Gritti L, Crooks D, Dombrowski Y. Oligodendrocytes in Development, Myelin Generation and Beyond. Cells. 2019;8(11):1424. doi: 10.3390/cells8111424Zhang SZ, Wang QQ, Yang QQ, Gu HY, Yin YQ, Li YD, Hou JC, Chen R, Sun QQ, Sun YF, Hu G, Zhou JW. NG2 glia regulate brain innate immunity via TGF-β2/TG-FBR2 axis. BMC Med. 2019;17(1):204. doi: 10.1186/s12916-019-1439-xZhang SZ, Wang QQ, Yang QQ, Gu HY, Yin YQ, Li YD, Hou JC, Chen R, Sun QQ, Sun YF, Hu G, Zhou JW. NG2 glia regulate brain innate immunity via TGF-β2/TG-FBR2 axis. BMC Med. 2019;17(1):204. doi: 10.1186/s12916-019-1439-xSeo JH, Maki T, Maeda M, Miyamoto N, Liang AC, Hayakawa K, Pham LD, Suwa F, Taguchi A, Matsuyama T, Ihara M, Kim KW, Lo EH, Arai K. Oligodendrocyte precursor cells support blood-brain barrier integrity via TGF-β signaling. PLoS One . 2014;9(7):e103174. doi: 10.1371/journal.pone.0103174Seo JH, Maki T, Maeda M, Miyamoto N, Liang AC, Hayakawa K, Pham LD, Suwa F, Taguchi A, Matsuyama T, Ihara M, Kim KW, Lo EH, Arai K. Oligodendrocyte precursor cells support blood-brain barrier integrity via TGF-β signaling. PLoS One . 2014;9(7):e103174. doi: 10.1371/journal.pone.0103174Palazuelos J, Klingener M, Aguirre A. TGFβ signaling regulates the timing of CNS myelination by modulating oligodendrocyte progenitor cell cycle exit through SMAD3/4/FoxO1/Sp1. J Neurosci. 2014;34(23):7917–7930. doi: 10.1523/JNEUROS-CI.0363-14.2014Palazuelos J, Klingener M, Aguirre A. TGFβ signaling regulates the timing of CNS myelination by modulating oligodendrocyte progenitor cell cycle exit through SMAD3/4/FoxO1/Sp1. J Neurosci. 2014;34(23):7917–7930. doi: 10.1523/JNEUROS-CI.0363-14.2014Vela JM, Molina-Holgado E, Arévalo-Martín A, Almazán G, Guaza C. Interleukin-1 regulates proliferation and differentiation of oligodendrocyte progenitor cells. Mol Cell Neurosci. 2002;20(3):489–502. doi: 10.1006/mcne.2002.1127Vela JM, Molina-Holgado E, Arévalo-Martín A, Almazán G, Guaza C. Interleukin-1 regulates proliferation and differentiation of oligodendrocyte progenitor cells. Mol Cell Neurosci. 2002;20(3):489–502. doi: 10.1006/mcne.2002.1127Matejuk A, Vandenbark AA, Offner H. Cross-Talk of the CNS With Immune Cells and Functions in Health and Disease. Front Neurol. 2021;12:672455. doi: 10.3389/fneur.2021.672455 PMID: 34135852; PMCID: PMC8200536.Matejuk A, Vandenbark AA, Offner H. Cross-Talk of the CNS With Immune Cells and Functions in Health and Disease. Front Neurol. 2021;12:672455. doi: 10.3389/fneur.2021.672455 PMID: 34135852; PMCID: PMC8200536.Seo JH, Miyamoto N, Hayakawa K, Pham LD, Maki T, Ayata C, Kim KW, Lo EH, Arai K. Oligodendrocyte precursors induce early blood-brain barrier opening after white matter injury. J Clin Invest . 2013;123(2):782– 786. doi: 10.1172/JCI65863Seo JH, Miyamoto N, Hayakawa K, Pham LD, Maki T, Ayata C, Kim KW, Lo EH, Arai K. Oligodendrocyte precursors induce early blood-brain barrier opening after white matter injury. J Clin Invest . 2013;123(2):782– 786. doi: 10.1172/JCI65863Gadani SP, Walsh JT, Smirnov I, Zheng J, Kipnis J. The gliaderived alarmin IL-33 orchestrates the immune response and promotes recovery following CNS injury. Neuron. 2015;85(4):703–709. doi: 10.1016/j.neuron.2015.01.01Gadani SP, Walsh JT, Smirnov I, Zheng J, Kipnis J. The gliaderived alarmin IL-33 orchestrates the immune response and promotes recovery following CNS injury. Neuron. 2015;85(4):703–709. doi: 10.1016/j.neuron.2015.01.01Laskaris LE, Di Biase MA, Everall I, Chana G, Christopoulos A, Skafidas E, Cropley VL, Pantelis C. Microglial activation and progressive brain changes in schizophrenia. Br J Pharmacol. 2016;173(4):666–680. doi: 10.1111/bph.13364Laskaris LE, Di Biase MA, Everall I, Chana G, Christopoulos A, Skafidas E, Cropley VL, Pantelis C. Microglial activation and progressive brain changes in schizophrenia. Br J Pharmacol. 2016;173(4):666–680. doi: 10.1111/bph.13364Chu T, Zhang YP, Tian Z, Ye C, Zhu M, Shields LBE, Kong M, Barnes GN, Shields CB, Cai J. Dynamic response of microglia/macrophage polarization following demyelination in mice. J Neuroinflammation . 2019;16(1):188. doi: 10.1186/s12974-019-1586-1Chu T, Zhang YP, Tian Z, Ye C, Zhu M, Shields LBE, Kong M, Barnes GN, Shields CB, Cai J. Dynamic response of microglia/macrophage polarization following demyelination in mice. J Neuroinflammation . 2019;16(1):188. doi: 10.1186/s12974-019-1586-1Li Y, Liu Z, Song Y, Pan JJ, Jiang Y, Shi X, Liu C, Ma Y, Luo L, Mamtilahun M, Shi Z, Khan H, Xie Q, Wang Y, Tang Y, Zhang Z, Yang GY. M2 microglia-derived extracellular vesicles promote white matter repair and functional recovery via miR-23a-5p after cerebral ischemia in mice. Theranostics. 2022;12(7):3553– 3573. doi: 10.7150/thno.68895Li Y, Liu Z, Song Y, Pan JJ, Jiang Y, Shi X, Liu C, Ma Y, Luo L, Mamtilahun M, Shi Z, Khan H, Xie Q, Wang Y, Tang Y, Zhang Z, Yang GY. M2 microglia-derived extracellular vesicles promote white matter repair and functional recovery via miR-23a-5p after cerebral ischemia in mice. Theranostics. 2022;12(7):3553– 3573. doi: 10.7150/thno.68895Miron VE, Boyd A, Zhao JW, Yuen TJ, Ruckh JM, Shadrach JL, van Wijngaarden P, Wagers AJ, Williams A, Franklin RJM, Ffrench-Constant C. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci . 2013;16(9):1211–1218. doi: 10.1038/nn.3469Miron VE, Boyd A, Zhao JW, Yuen TJ, Ruckh JM, Shadrach JL, van Wijngaarden P, Wagers AJ, Williams A, Franklin RJM, Ffrench-Constant C. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci . 2013;16(9):1211–1218. doi: 10.1038/nn.3469Kronenberg J, Pars K, Brieskorn M, Prajeeth CK, Heckers S, Schwenkenbecher P, Skripuletz T, Pul R, Pavlou A, Stangel M. Fumaric Acids Directly Influence Gene Expression of Neuroprotective Factors in Rodent Microglia. Int J Mol Sci. 2019;20(2):325. doi: 10.3390/ijms20020325Kronenberg J, Pars K, Brieskorn M, Prajeeth CK, Heckers S, Schwenkenbecher P, Skripuletz T, Pul R, Pavlou A, Stangel M. Fumaric Acids Directly Influence Gene Expression of Neuroprotective Factors in Rodent Microglia. Int J Mol Sci. 2019;20(2):325. doi: 10.3390/ijms20020325Taylor DL, Pirianov G, Holland S, McGinnity CJ, Norman AL, Reali C, Diemel LT, Gveric D, Yeung D, Mehmet H. Attenuation of proliferation in oligodendrocyte precursor cells by activated microglia. J Neurosci Res. 2010;88(8):1632–1644. doi: 10.1002/jnr.22335Taylor DL, Pirianov G, Holland S, McGinnity CJ, Norman AL, Reali C, Diemel LT, Gveric D, Yeung D, Mehmet H. Attenuation of proliferation in oligodendrocyte precursor cells by activated microglia. J Neurosci Res. 2010;88(8):1632–1644. doi: 10.1002/jnr.22335Plastini MJ, HL, Brambilla R. Dynamic Responses of Microglia in Animal Models of Multiple Sclerosis. Front Cell Neurosci . 2020;14:269. doi: 10.3389/fn-cel.2020.00269Plastini MJ, HL, Brambilla R. Dynamic Responses of Microglia in Animal Models of Multiple Sclerosis. Front Cell Neurosci . 2020;14:269. doi: 10.3389/fn-cel.2020.00269Kirby L, Jin J, Cardona JG, Smith MD, Martin KA, Wang J, Strasburger H, Herbst L, Alexis M, Karnell J, Davidson T, Dutta R, Goverman J, Bergles D, Calabresi PA. Oligodendrocyte precursor cells present antigen and are cytotoxic targets in inflammatory demyelination. Nat Commun. 2019;10(1):3887. doi: 10.1038/s41467-019-11638-3Kirby L, Jin J, Cardona JG, Smith MD, Martin KA, Wang J, Strasburger H, Herbst L, Alexis M, Karnell J, Davidson T, Dutta R, Goverman J, Bergles D, Calabresi PA. Oligodendrocyte precursor cells present antigen and are cytotoxic targets in inflammatory demyelination. Nat Commun. 2019;10(1):3887. doi: 10.1038/s41467-019-11638-3Goldsmith DR, Bekhbat M, Mehta ND, Felger JC. Inflammation-Related Functional and Structural Dysconnectivity as a Pathway to Psychopathology. Biol Psychiatry . 2023;93(5):405–418. doi: 10.1016/j.biopsych.2022.11.003 Epub 2022 Nov 9. PMID: 36725140; PMCID: PMC9895884.Goldsmith DR, Bekhbat M, Mehta ND, Felger JC. Inflammation-Related Functional and Structural Dysconnectivity as a Pathway to Psychopathology. Biol Psychiatry . 2023;93(5):405–418. doi: 10.1016/j.biopsych.2022.11.003 Epub 2022 Nov 9. PMID: 36725140; PMCID: PMC9895884.Michalczyk A, Tyburski E, Podwalski P, Waszczuk K, Rudkowski K, Kucharska-Mazur J, Mak M, Rek-Owodziń K, Plichta P, Bielecki M, Andrusewicz W, Cecerska-Heryć E, Samochowiec A, Misiak B, Sagan L, Samochowiec J. Serum Inflammatory Markers and Their Associations with the Integrity of the Cingulum Bundle in Schizophrenia, from Prodromal Stages to Chronic Psychosis. J Clin Med. 2022;11(21):6352. doi: 10.3390/jcm11216352Michalczyk A, Tyburski E, Podwalski P, Waszczuk K, Rudkowski K, Kucharska-Mazur J, Mak M, Rek-Owodziń K, Plichta P, Bielecki M, Andrusewicz W, Cecerska-Heryć E, Samochowiec A, Misiak B, Sagan L, Samochowiec J. Serum Inflammatory Markers and Their Associations with the Integrity of the Cingulum Bundle in Schizophrenia, from Prodromal Stages to Chronic Psychosis. J Clin Med. 2022;11(21):6352. doi: 10.3390/jcm11216352Waszczuk K, Rek-Owodziń K, Tyburski E, Mak M, Misiak B, Samochowiec J. Disturbances in White Matter Integrity in the Ultra-High-Risk Psychosis State — A Systematic Review. J Clin Med . 2021;10:2515. doi: 10.3390/jcm10112515Waszczuk K, Rek-Owodziń K, Tyburski E, Mak M, Misiak B, Samochowiec J. Disturbances in White Matter Integrity in the Ultra-High-Risk Psychosis State — A Systematic Review. J Clin Med . 2021;10:2515. doi: 10.3390/jcm10112515Howes D, McCutcheon R. Inflammation and the neural diathesis-stress hypothesis of schizophrenia: a reconceptualization. Transl Psychiatr y. 2017;7(2):e1024. doi: 10.1038/tp.2016.278Howes D, McCutcheon R. Inflammation and the neural diathesis-stress hypothesis of schizophrenia: a reconceptualization. Transl Psychiatr y. 2017;7(2):e1024. doi: 10.1038/tp.2016.278Deczkowska A, Keren-Shaul H, Weiner A, Colonna M, Schwartz M, Amit I. Disease-Associated Microglia: A Universal Immune Sensor of Neurodegeneration. Cell. 2018;173(5):1073–1081. doi: 10.1016/j.cell.2018.05.003Deczkowska A, Keren-Shaul H, Weiner A, Colonna M, Schwartz M, Amit I. Disease-Associated Microglia: A Universal Immune Sensor of Neurodegeneration. Cell. 2018;173(5):1073–1081. doi: 10.1016/j.cell.2018.05.003Gober R, Ardalan M, Shiadeh SMJ, Duque L, Garamszegi SP, Ascona M, Barreda A, Sun X, Mallard C, Vontell RT. Microglia activation in postmortem brains with schizophrenia demonstrates distinct morphological changes between brain regions. Brain Pathol . 2022;32(1):e13003. doi: 10.1111/bpa.13003Gober R, Ardalan M, Shiadeh SMJ, Duque L, Garamszegi SP, Ascona M, Barreda A, Sun X, Mallard C, Vontell RT. Microglia activation in postmortem brains with schizophrenia demonstrates distinct morphological changes between brain regions. Brain Pathol . 2022;32(1):e13003. doi: 10.1111/bpa.13003Uranova NA, Vikhreva OV, Rakhmanova VI. Abnormal microglial reactivity in gray matter of the prefrontal cortex in schizophrenia. Asian J Psychiatr. 2021;3:102752. doi: 10.1016/j.ajp.2021.102752Uranova NA, Vikhreva OV, Rakhmanova VI. Abnormal microglial reactivity in gray matter of the prefrontal cortex in schizophrenia. Asian J Psychiatr. 2021;3:102752. doi: 10.1016/j.ajp.2021.102752St-Pierre MK, Šimončičová E, Bögi E, Tremblay MÈ. Shedding Light on the Dark Side of the Microglia. ASN Neuro . 2020;12:1759091420925335. doi: 10.1177/1759091420925335St-Pierre MK, Šimončičová E, Bögi E, Tremblay MÈ. Shedding Light on the Dark Side of the Microglia. ASN Neuro . 2020;12:1759091420925335. doi: 10.1177/1759091420925335Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE, Jones T, Banati RB. In-vivo measurement of activated microglia in dementia. Lancet. 2001;358(9280):461–467. doi: 10.1016/S0140-6736(01)05625-2Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE, Jones T, Banati RB. In-vivo measurement of activated microglia in dementia. Lancet. 2001;358(9280):461–467. doi: 10.1016/S0140-6736(01)05625-2Pasternak O, Kubicki M, Shenton ME. In vivo imaging of neuroinflammation in schizophrenia. Schizophr Res. 2016;173(3):200–212. doi: 10.1016/j.schres.2015.05.034 Epub 2015 Jun 3. PMID: 26048294; PMCID: PMC4668243.Pasternak O, Kubicki M, Shenton ME. In vivo imaging of neuroinflammation in schizophrenia. Schizophr Res. 2016;173(3):200–212. doi: 10.1016/j.schres.2015.05.034 Epub 2015 Jun 3. PMID: 26048294; PMCID: PMC4668243.Bishop JR, Zhang L, Lizano P. Inflammation Subtypes and Translating Inflammation-Related Genetic Findings in Schizophrenia and Related Psychoses: A Perspective on Pathways for Treatment Stratifation and Novel Therapies. Harv Rev Psychiatry . 2022;30(1):59– 70. doi: 10.1097/HRP.0000000000000321Bishop JR, Zhang L, Lizano P. Inflammation Subtypes and Translating Inflammation-Related Genetic Findings in Schizophrenia and Related Psychoses: A Perspective on Pathways for Treatment Stratifation and Novel Therapies. Harv Rev Psychiatry . 2022;30(1):59– 70. doi: 10.1097/HRP.0000000000000321Stamoula Ε, Ainatzoglou A, Stamatellos VP, Dardalas I, Siafis S, Matsas A, Stamoulas K, Papazisis G. Atypical antipsychotics in multiple sclerosis: A review of their in vivo immunomodulatory effects. Mult Scler Relat Disord. 2022;58:103522. doi: 10.1016/j.msard.2022.103522Stamoula Ε, Ainatzoglou A, Stamatellos VP, Dardalas I, Siafis S, Matsas A, Stamoulas K, Papazisis G. Atypical antipsychotics in multiple sclerosis: A review of their in vivo immunomodulatory effects. Mult Scler Relat Disord. 2022;58:103522. doi: 10.1016/j.msard.2022.103522Ceylan U, Haupeltshofer S, Kämper L, Dann J, Ambrosius B, Gold R, Faissner S. Clozapine Regulates Microglia and Is Effective in Chronic Experimental Autoimmune Encephalomyelitis. Front Immunol. 2021;12:656941. doi: 10.3389/fimmu.2021.656941Ceylan U, Haupeltshofer S, Kämper L, Dann J, Ambrosius B, Gold R, Faissner S. Clozapine Regulates Microglia and Is Effective in Chronic Experimental Autoimmune Encephalomyelitis. Front Immunol. 2021;12:656941. doi: 10.3389/fimmu.2021.656941O’Sullivan D, Green L, Stone S, Zareie P, Kharkrang M, Fong D, Connor B, La Flamme AC. Treatment with the antipsychotic agent, risperidone, reduces disease severity in experimental autoimmune encephalomy-elitis. PLoS One . 2014;9(8):e104430. doi: 10.1371/journal.pone.0104430O’Sullivan D, Green L, Stone S, Zareie P, Kharkrang M, Fong D, Connor B, La Flamme AC. Treatment with the antipsychotic agent, risperidone, reduces disease severity in experimental autoimmune encephalomy-elitis. PLoS One . 2014;9(8):e104430. doi: 10.1371/journal.pone.0104430Zhornitsky S, Yong V W, Koch MW, Mackie A, Potvin S, Patten SB, Metz LM. Quetiapine Fumarate for the Treatment of Multiple Sclerosis: Focus on Myelin Repair. CNS Neurosci Ther . 2013;19(10):737–744. doi: 10.1111/cns.12154Zhornitsky S, Yong V W, Koch MW, Mackie A, Potvin S, Patten SB, Metz LM. Quetiapine Fumarate for the Treatment of Multiple Sclerosis: Focus on Myelin Repair. CNS Neurosci Ther . 2013;19(10):737–744. doi: 10.1111/cns.12154Xiao L, Xu H, Zhang Y, Wei Z, He J, Jiang W, Li X, Dyck LE, Devon RM, Deng Y, Li XM. Quetiapine facilitates oligodendrocyte development and prevents mice from myelin breakdown and behavioral changes. Mol Psychiatry. 2008;13(7):697–708. doi: 10.1038/sj.mp.4002064Xiao L, Xu H, Zhang Y, Wei Z, He J, Jiang W, Li X, Dyck LE, Devon RM, Deng Y, Li XM. Quetiapine facilitates oligodendrocyte development and prevents mice from myelin breakdown and behavioral changes. Mol Psychiatry. 2008;13(7):697–708. doi: 10.1038/sj.mp.4002064Zhang Y, Zhang H, Wang L, Jiang W, Xu H, Xiao L, Bi X, Wang J, Zhu S, Zhang R, He J, Tan Q, Zhang D, Kong J, Li XM. Quetiapine enhances oligodendrocyte regeneration and myelin repair after cuprizone-induced demyelination. Schizophr Res . 2012;138(1):8–17. doi: 10.1016/j.schres.2012.04.006Zhang Y, Zhang H, Wang L, Jiang W, Xu H, Xiao L, Bi X, Wang J, Zhu S, Zhang R, He J, Tan Q, Zhang D, Kong J, Li XM. Quetiapine enhances oligodendrocyte regeneration and myelin repair after cuprizone-induced demyelination. Schizophr Res . 2012;138(1):8–17. doi: 10.1016/j.schres.2012.04.006Bi X, Zhang Y, Yan B, Fang S, He J, Zhang D, Zhang Z, Kong J, Tan Q, Li XM. Quetiapine prevents oligodendrocyte and myelin loss and promotes maturation of oligodendrocyte progenitors in the hippocampus of global cerebral ischemia mice. J Neurochem. 2012;123(1):14–20. doi: 10.1111/j.1471-4159.2012.07883.xBi X, Zhang Y, Yan B, Fang S, He J, Zhang D, Zhang Z, Kong J, Tan Q, Li XM. Quetiapine prevents oligodendrocyte and myelin loss and promotes maturation of oligodendrocyte progenitors in the hippocampus of global cerebral ischemia mice. J Neurochem. 2012;123(1):14–20. doi: 10.1111/j.1471-4159.2012.07883.xMei F, Guo S, He Y, Wang L, Wang H, Niu J, Kong J, Li X, Wu Y, Xiao L. Quetiapine, an atypical antipsychotic, is protective against autoimmune-mediated demyelination by inhibiting effector T cell proliferation. PLoS One . 2012;7(8):e42746. doi: 10.1371/journal.pone.0042746Mei F, Guo S, He Y, Wang L, Wang H, Niu J, Kong J, Li X, Wu Y, Xiao L. Quetiapine, an atypical antipsychotic, is protective against autoimmune-mediated demyelination by inhibiting effector T cell proliferation. PLoS One . 2012;7(8):e42746. doi: 10.1371/journal.pone.0042746Shao Y, Peng H, Huang Q, Kong J, Xu H. Quetiapine mitigates the neuroinflammation and oligodendrocyte loss in the brain of C57BL/6 mouse following cuprizone exposure for one week. Eur J Pharmacol . 2015;765:249–257. doi: 10.1016/j.ejphar.2015.08.046Shao Y, Peng H, Huang Q, Kong J, Xu H. Quetiapine mitigates the neuroinflammation and oligodendrocyte loss in the brain of C57BL/6 mouse following cuprizone exposure for one week. Eur J Pharmacol . 2015;765:249–257. doi: 10.1016/j.ejphar.2015.08.046Wang H, Liu S, Tian Y, Wu X, He Y, Li C, Namaka M, Kong J, Li H, Xiao L. Quetiapine Inhibits Microglial Activation by Neutralizing Abnormal STIM1-Mediated Intercellular Calcium Homeostasis and Promotes Myelin Repair in a Cuprizone-Induced Mouse Model of Demyelination. Front Cell Neurosci . 2015;9:492. doi: 10.3389/fncel.2015.0049Wang H, Liu S, Tian Y, Wu X, He Y, Li C, Namaka M, Kong J, Li H, Xiao L. Quetiapine Inhibits Microglial Activation by Neutralizing Abnormal STIM1-Mediated Intercellular Calcium Homeostasis and Promotes Myelin Repair in a Cuprizone-Induced Mouse Model of Demyelination. Front Cell Neurosci . 2015;9:492. doi: 10.3389/fncel.2015.0049Zhu S, Shi R, Li V, Wang J, Zhang R, Tempier A, He J, Kong J, Wang JF, Li XM. Quetiapine attenuates glial activation and proinflammatory cytokines in APP/PS1 transgenic mice via inhibition of nuclear factor-κB pathway. Int J Neuropsychopharmacol. 2014;18(3):pyu022. doi: 10.1093/ijnp/pyu022 PMID: 25618401; PMCID: PMC4360237.Zhu S, Shi R, Li V, Wang J, Zhang R, Tempier A, He J, Kong J, Wang JF, Li XM. Quetiapine attenuates glial activation and proinflammatory cytokines in APP/PS1 transgenic mice via inhibition of nuclear factor-κB pathway. Int J Neuropsychopharmacol. 2014;18(3):pyu022. doi: 10.1093/ijnp/pyu022 PMID: 25618401; PMCID: PMC4360237.Bian Q, Kato T, Monji A, Hashioka S, Mizoguchi Y, Horikawa H, Kanba S. The effect of atypical antipsychotics, perospirone, ziprasidone and quetiapine on microglial activation induced by interferon-gamma. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(1):42–58. doi: 10.1016/j.pnpbp.2007.06.031Bian Q, Kato T, Monji A, Hashioka S, Mizoguchi Y, Horikawa H, Kanba S. The effect of atypical antipsychotics, perospirone, ziprasidone and quetiapine on microglial activation induced by interferon-gamma. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(1):42–58. doi: 10.1016/j.pnpbp.2007.06.031Himmerich H, Schönherr J, Fulda S, Sheldrick AJ, Bauer K , S ack U. Imp ac t of ant ip s ychot ic s on c y t ok ine production in vitro. J Psychiatr Res . 2011;45(10):1358– 1365. doi: 10.1016/j.jpsychires.2011.04.009Himmerich H, Schönherr J, Fulda S, Sheldrick AJ, Bauer K , S ack U. Imp ac t of ant ip s ychot ic s on c y t ok ine production in vitro. J Psychiatr Res . 2011;45(10):1358– 1365. doi: 10.1016/j.jpsychires.2011.04.009Xu H, Yang HJ, McConomy B, Browning R, Li XM. Behavioral and neurobiological changes in C57BL/6 mouse exposed to cuprizone: effects of antipsychotics. Front Behav Neurosci. 2010;4:8. doi: 10.3389/fn-beh.2010.00008Xu H, Yang HJ, McConomy B, Browning R, Li XM. Behavioral and neurobiological changes in C57BL/6 mouse exposed to cuprizone: effects of antipsychotics. Front Behav Neurosci. 2010;4:8. doi: 10.3389/fn-beh.2010.00008Matsushima GK, Morell P. The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system. Brain Pathol . 2001;11(1):107–116. doi: 10.1111/j.1750-3639.2001.tb00385.xMatsushima GK, Morell P. The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system. Brain Pathol . 2001;11(1):107–116. doi: 10.1111/j.1750-3639.2001.tb00385.xTempleton N, Kivell B, McCaughey-Chapman A, Connor B, La Flamme AC. Clozapine administration enhanced functional recovery after cuprizone demyelination. PLoS One. 2019;14(5):e0216113. doi: 10.1371/journal.pone.0216113 PMID: 31071102; PMCID: PMC6508663.Templeton N, Kivell B, McCaughey-Chapman A, Connor B, La Flamme AC. Clozapine administration enhanced functional recovery after cuprizone demyelination. PLoS One. 2019;14(5):e0216113. doi: 10.1371/journal.pone.0216113 PMID: 31071102; PMCID: PMC6508663.Madsen PM, Desu HL, de Rivero Vaccari JP, Florimon Y, Ellman DG, Keane RW, Clausen BH, Lambertsen KL, Brambilla R. Oligodendrocytes modulate the immune-inflammatory response in EAE via TNFR2 signaling. Brain Behav Immun. 2020;84:132–146. doi: 10.1016/j.bbi.2019.11.017Madsen PM, Desu HL, de Rivero Vaccari JP, Florimon Y, Ellman DG, Keane RW, Clausen BH, Lambertsen KL, Brambilla R. Oligodendrocytes modulate the immune-inflammatory response in EAE via TNFR2 signaling. Brain Behav Immun. 2020;84:132–146. doi: 10.1016/j.bbi.2019.11.017Arnett HA, Mason J, Marino M, Suzuki K, Matsushima GK, Ting JP. TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination. Nat Neurosci. 2001;4(11):1116–1122. doi: 10.1038/nn738 PMID: 11600888.Arnett HA, Mason J, Marino M, Suzuki K, Matsushima GK, Ting JP. TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination. Nat Neurosci. 2001;4(11):1116–1122. doi: 10.1038/nn738 PMID: 11600888.Robichon K, Patel V, Connor B, La Flamme AC. Clozapine reduces inflltration into the CNS by targeting migration in experimental autoimmune encephalomyelitis. J Neuroinflammation . 2020;17(1):53. doi: 10.1186/s12974-020-01733-4Robichon K, Patel V, Connor B, La Flamme AC. Clozapine reduces inflltration into the CNS by targeting migration in experimental autoimmune encephalomyelitis. J Neuroinflammation . 2020;17(1):53. doi: 10.1186/s12974-020-01733-4Zhu F, Zheng Y, Ding YQ, Liu Y, Zhang X, Wu R, Guo X, Zhao J. Minocycline and risperidone prevent microglia activation and rescue behavioral deficits induced by neonatal intrahippocampal injection of lipopoly-saccharide in rats. PLoS One . 2014;9(4):e93966. doi: 10.1371/journal.pone.0093966Zhu F, Zheng Y, Ding YQ, Liu Y, Zhang X, Wu R, Guo X, Zhao J. Minocycline and risperidone prevent microglia activation and rescue behavioral deficits induced by neonatal intrahippocampal injection of lipopoly-saccharide in rats. PLoS One . 2014;9(4):e93966. doi: 10.1371/journal.pone.0093966Racki V, Marcelic M, Stimac I, Petric D, Kucic N. Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells. Int J Mol Sci. 2021;22(9):4399. doi: 10.3390/ijms22094399Racki V, Marcelic M, Stimac I, Petric D, Kucic N. Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells. Int J Mol Sci. 2021;22(9):4399. doi: 10.3390/ijms22094399Zhang H, Zhang Y, Xu H, Wang L, Adilijiang A, Wang J, Hartle K, Zhang Z, Zhang D, Tan Q, Kong J, Huang Q, Li XM. Olanzapine ameliorates neuropathological changes and increases IGF-1 expression in frontal cortex of C57BL/6 mice exposed to cuprizone. Psychiatry Res . 2014;216(3):438–445. doi: 10.1016/j.psychres.2014.02.019Zhang H, Zhang Y, Xu H, Wang L, Adilijiang A, Wang J, Hartle K, Zhang Z, Zhang D, Tan Q, Kong J, Huang Q, Li XM. Olanzapine ameliorates neuropathological changes and increases IGF-1 expression in frontal cortex of C57BL/6 mice exposed to cuprizone. Psychiatry Res . 2014;216(3):438–445. doi: 10.1016/j.psychres.2014.02.019Kimoto S, Okuda A, Toritsuka M, Yamauchi T, Makinodan M, Okuda H, Tatsumi K, Nakamura Y, Wanaka A, Kishimoto T. Olanzapine stimulates proliferation but inhibits differentiation in rat oligodendrocyte precursor cell cultures. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(8):1950–1956. doi: 10.1016/j.pnpbp.2011.07.011Kimoto S, Okuda A, Toritsuka M, Yamauchi T, Makinodan M, Okuda H, Tatsumi K, Nakamura Y, Wanaka A, Kishimoto T. Olanzapine stimulates proliferation but inhibits differentiation in rat oligodendrocyte precursor cell cultures. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(8):1950–1956. doi: 10.1016/j.pnpbp.2011.07.011Fang F, Zhang H, Zhang Y, Xu H, Huang Q, Adilijiang A, Wang J, Zhang Z, Zhang D, Tan Q, He J, Kong L, Liu Y, Li XM. Antipsychotics promote the differentiation of oligodendrocyte progenitor cells by regulating oligodendrocyte lineage transcription factors 1 and 2. Life Sci . 2013;93(12–14):429–434. doi: 10.1016/j.lfs.2013.08.004Fang F, Zhang H, Zhang Y, Xu H, Huang Q, Adilijiang A, Wang J, Zhang Z, Zhang D, Tan Q, He J, Kong L, Liu Y, Li XM. Antipsychotics promote the differentiation of oligodendrocyte progenitor cells by regulating oligodendrocyte lineage transcription factors 1 and 2. Life Sci . 2013;93(12–14):429–434. doi: 10.1016/j.lfs.2013.08.004Zhang H, Zhang Y, Xu H, Wang L, Adilijiang A, Wang J, Hartle K, Zhang Z, Zhang D, Tan Q, Kong J, Huang Q, Li XM. Olanzapine ameliorates neuropathological changes and increases IGF-1 expression in frontal cortex of C57BL/6 mice exposed to cuprizone. Psychiatry Res. 2014;216(3):438–445. doi: 10.1016/j.psychres.2014.02.019Zhang H, Zhang Y, Xu H, Wang L, Adilijiang A, Wang J, Hartle K, Zhang Z, Zhang D, Tan Q, Kong J, Huang Q, Li XM. Olanzapine ameliorates neuropathological changes and increases IGF-1 expression in frontal cortex of C57BL/6 mice exposed to cuprizone. Psychiatry Res. 2014;216(3):438–445. doi: 10.1016/j.psychres.2014.02.019Ersland KM, Skrede S, Stansberg C, Steen VM. Subchronic olanzapine exposure leads to increased expression of myelination-related genes in rat fron-to-medial cortex. Transl Psychiatr y . 2017;7(11):1262. doi: 10.1038/s41398-017-0008-3Ersland KM, Skrede S, Stansberg C, Steen VM. Subchronic olanzapine exposure leads to increased expression of myelination-related genes in rat fron-to-medial cortex. Transl Psychiatr y . 2017;7(11):1262. doi: 10.1038/s41398-017-0008-3Burghardt KJ, Khoury AS, Msallaty Z, Yi Z, Seyoum B. Antipsychotic Medications and DNA Methylation in Schizophrenia and Bipolar Disorder: A Systematic Review. Pharmacotherapy. 2020;40(4):331–342. doi: 10.1002/phar.2375Burghardt KJ, Khoury AS, Msallaty Z, Yi Z, Seyoum B. Antipsychotic Medications and DNA Methylation in Schizophrenia and Bipolar Disorder: A Systematic Review. Pharmacotherapy. 2020;40(4):331–342. doi: 10.1002/phar.2375Leroux E, Vandevelde A, Tréhout M, Dollfus S. Abnormalities of fronto-subcortical pathways in schizophrenia and the differential impacts of antipsychotic treatment: a DTI-based tractography study. Psychiatry Res Neuroimaging. 2018;280:22–29. doi: 10.1016/j.pscychresns.2018.08.008Leroux E, Vandevelde A, Tréhout M, Dollfus S. Abnormalities of fronto-subcortical pathways in schizophrenia and the differential impacts of antipsychotic treatment: a DTI-based tractography study. Psychiatry Res Neuroimaging. 2018;280:22–29. doi: 10.1016/j.pscychresns.2018.08.008Luo C, Lencer R, Hu N, Xiao Y, Zhang W, Li S, Lui S, Gong Q. Characteristics of White Matter Structural Networks in Chronic Schizophrenia Treated with Clozapine or Risperidone and Those Never Treated. Int J Neuropsychopharmacol . 2020;23(12):799–810. doi: 10.1093/ijnp/pyaa061Luo C, Lencer R, Hu N, Xiao Y, Zhang W, Li S, Lui S, Gong Q. Characteristics of White Matter Structural Networks in Chronic Schizophrenia Treated with Clozapine or Risperidone and Those Never Treated. Int J Neuropsychopharmacol . 2020;23(12):799–810. doi: 10.1093/ijnp/pyaa061Hu ML, Zong XF, Zheng JJ, Pantazatos SP, Miller JM, Li ZC, Liao YH, He Y, Zhou J, Sang DE, Zhao HZ, Lv LX, Tang JS, Mann JJ, Chen XG. Short-term Effects of Risperidone Monotherapy on Spontaneous Brain Activ ity in First-episode Treatment-naïve Schizophrenia Patients: A Longitudinal fMRI Study. Sci Rep. 2016;6:34287. doi: 10.1038/srep34287Hu ML, Zong XF, Zheng JJ, Pantazatos SP, Miller JM, Li ZC, Liao YH, He Y, Zhou J, Sang DE, Zhao HZ, Lv LX, Tang JS, Mann JJ, Chen XG. Short-term Effects of Risperidone Monotherapy on Spontaneous Brain Activ ity in First-episode Treatment-naïve Schizophrenia Patients: A Longitudinal fMRI Study. Sci Rep. 2016;6:34287. doi: 10.1038/srep34287Wu R, Ou Y, Liu F, Chen J, Li H, Zhao J, Guo W, Fan X. Reduced Brain Activity in the Right Putamen as an Early Predictor for Treatment Response in Drug-Naive, First-Episode Schizophrenia. Front Psychiatry . 2019;10:741. doi: 10.3389/fpsyt.2019.00741Wu R, Ou Y, Liu F, Chen J, Li H, Zhao J, Guo W, Fan X. Reduced Brain Activity in the Right Putamen as an Early Predictor for Treatment Response in Drug-Naive, First-Episode Schizophrenia. Front Psychiatry . 2019;10:741. doi: 10.3389/fpsyt.2019.00741Aringhieri S, Carli M, Kolachalam S, Verdesca V, Cini E, Rossi M, McCormick PJ, Corsini GU, Maggio R, Scarselli M. Molecular targets of atypical antipsychotics: From mechanism of action to clinical differences. Pharmacol Ther. 2018;192:20–41. doi: 10.1016/j.pharmthera.2018.06.012Aringhieri S, Carli M, Kolachalam S, Verdesca V, Cini E, Rossi M, McCormick PJ, Corsini GU, Maggio R, Scarselli M. Molecular targets of atypical antipsychotics: From mechanism of action to clinical differences. Pharmacol Ther. 2018;192:20–41. doi: 10.1016/j.pharmthera.2018.06.012Arnt J, Skarsfeldt T. Do novel ant ipsychot ics have similar pharmacological characteristics? A review of the evidence. Neuropsychopharmacology. 1998;18(2):63– 101. doi: 10.1016/S0893-133X(97)00112-7Arnt J, Skarsfeldt T. Do novel ant ipsychot ics have similar pharmacological characteristics? A review of the evidence. Neuropsychopharmacology. 1998;18(2):63– 101. doi: 10.1016/S0893-133X(97)00112-7Bymaster FP, Felder CC, Tzavara E, Nomikos GG, Calligaro DO, Mckinzie DL. Muscarinic mechanisms of antipsychotic atypicality. Prog Neuropsycho-pharmacol Biol Psychiatry . 2003;27(7):1125–1143. doi: 10.1016/j.pnpbp.2003.09.008 PMID: 14642972Bymaster FP, Felder CC, Tzavara E, Nomikos GG, Calligaro DO, Mckinzie DL. Muscarinic mechanisms of antipsychotic atypicality. Prog Neuropsycho-pharmacol Biol Psychiatry . 2003;27(7):1125–1143. doi: 10.1016/j.pnpbp.2003.09.008 PMID: 14642972Marinelli C, Bertalot T, Zusso M, Skaper SD, Giusti P. Systematic Review of Pharmacological Properties of the Oligodendrocyte Lineage. Front Cell Neurosci. 2016;10:27. doi: 10.3389/fncel.2016.00027Marinelli C, Bertalot T, Zusso M, Skaper SD, Giusti P. Systematic Review of Pharmacological Properties of the Oligodendrocyte Lineage. Front Cell Neurosci. 2016;10:27. doi: 10.3389/fncel.2016.00027Choi MH, Na JE, Yoon YR, Lee HJ, Yoon S, Rhyu IJ, Baik JH. Role of Dopamine D2 Receptor in Stress-Induced Myelin Loss. Sci Rep. 2017;7(1):11654. doi: 10.1038/s41598-017-10173-9 Erratum in: Sci Rep. 2018;8(1):6055.Choi MH, Na JE, Yoon YR, Lee HJ, Yoon S, Rhyu IJ, Baik JH. Role of Dopamine D2 Receptor in Stress-Induced Myelin Loss. Sci Rep. 2017;7(1):11654. doi: 10.1038/s41598-017-10173-9 Erratum in: Sci Rep. 2018;8(1):6055.Pani L, Porcella A, Gessa GL. The role of stress in the pathophysiology of the dopaminergic system. Mol Psychiatry. 2000;5(1):14–21. doi: 10.1038/sj.mp.4000589Pani L, Porcella A, Gessa GL. The role of stress in the pathophysiology of the dopaminergic system. Mol Psychiatry. 2000;5(1):14–21. doi: 10.1038/sj.mp.4000589Bongarzone ER, Howard SG, Schonmann V, Campagnoni AT. Identification of the dopamine D3 receptor in oligodendrocyte precursors: potential role in regulating differentiation and myelin formation. J Neurosci. 1998;18(14):5344–5353. doi: 10.1523/JNEUROSCI.18-14-05344.1998Bongarzone ER, Howard SG, Schonmann V, Campagnoni AT. Identification of the dopamine D3 receptor in oligodendrocyte precursors: potential role in regulating differentiation and myelin formation. J Neurosci. 1998;18(14):5344–5353. doi: 10.1523/JNEUROSCI.18-14-05344.1998Todd RD. Neural development is regulated by classical neurotransmitters: dopamine D2 receptor stimulation enhances neurite outgrowth. Biol Psychiatry . 1992;31(8):794–807. doi: 10.1016/0006-3223(92)90311-mTodd RD. Neural development is regulated by classical neurotransmitters: dopamine D2 receptor stimulation enhances neurite outgrowth. Biol Psychiatry . 1992;31(8):794–807. doi: 10.1016/0006-3223(92)90311-mMitelman SA, Buchsbaum MS, Christian BT, Merrill BM, Buchsbaum BR, Mukherjee J, Lehrer DS. Dopamine receptor density and white mater integrity: F-fally-pride positron emission tomography and diffusion tensor imaging study in healthy and schizophrenia subjects. Brain Imaging Behav. 2020;14(3):736–752. doi: 10.1007/s11682-018-0012-0Mitelman SA, Buchsbaum MS, Christian BT, Merrill BM, Buchsbaum BR, Mukherjee J, Lehrer DS. Dopamine receptor density and white mater integrity: F-fally-pride positron emission tomography and diffusion tensor imaging study in healthy and schizophrenia subjects. Brain Imaging Behav. 2020;14(3):736–752. doi: 10.1007/s11682-018-0012-0Hrvatin S, Hochbaum DR, Nagy MA, Cicconet M, Robertson K, Cheadle L, Zilionis R, Ratner A, Borges-Monroy R, Klein AM, Sabatini BL, Greenberg ME. Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex. Nat Neurosci. 2018;21(1):120–129. doi: 10.1038/s41593-017-0029-5Hrvatin S, Hochbaum DR, Nagy MA, Cicconet M, Robertson K, Cheadle L, Zilionis R, Ratner A, Borges-Monroy R, Klein AM, Sabatini BL, Greenberg ME. Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex. Nat Neurosci. 2018;21(1):120–129. doi: 10.1038/s41593-017-0029-5Damiano S, La Rosa G, Sozio C, Cavaliere G, Trinchese G, Raia M, Paternò R, Mollica MP, Avvedimento VE, Santillo M. 5-Hydroxytryptamine Modulates Maturation and Mitochondria Function of Human Oligodendrocyte Progenitor M03-13 Cells. Int J Mol Sci. 2021;22(5):2621. doi: 10.3390/ijms22052621Damiano S, La Rosa G, Sozio C, Cavaliere G, Trinchese G, Raia M, Paternò R, Mollica MP, Avvedimento VE, Santillo M. 5-Hydroxytryptamine Modulates Maturation and Mitochondria Function of Human Oligodendrocyte Progenitor M03-13 Cells. Int J Mol Sci. 2021;22(5):2621. doi: 10.3390/ijms22052621Fan LW, Bhatt A, Tien LT, Zheng B, Simpson KL, Lin RC, Cai Z, Kumar P, Pang Y. Exposure to serotonin adversely affects oligodendrocyte development and myelination in vitro. J Neurochem. 2015;133(4):532–543. doi: 10.1111/jnc.12988Fan LW, Bhatt A, Tien LT, Zheng B, Simpson KL, Lin RC, Cai Z, Kumar P, Pang Y. Exposure to serotonin adversely affects oligodendrocyte development and myelination in vitro. J Neurochem. 2015;133(4):532–543. doi: 10.1111/jnc.12988Thoma s Broome S , L ouangaphay K , Keay K A , L egg io GM , Musumeci G, Castorina A. Dopamine: an immune transmitter. Neural Regen Res. 2020;15(12):2173– 2185. doi: 10.4103/1673-5374.284976Thoma s Broome S , L ouangaphay K , Keay K A , L egg io GM , Musumeci G, Castorina A. Dopamine: an immune transmitter. Neural Regen Res. 2020;15(12):2173– 2185. doi: 10.4103/1673-5374.284976Channer B, Matt SM, Nickoloff-Bybel EA, Pappa V, Agarwal Y, Wickman J, Gaskill PJ. Dopamine, Immunity, and Disease. Pharmacol Rev . 2023;75(1):62–158. doi: 10.1124/pharmrev.122.000618Channer B, Matt SM, Nickoloff-Bybel EA, Pappa V, Agarwal Y, Wickman J, Gaskill PJ. Dopamine, Immunity, and Disease. Pharmacol Rev . 2023;75(1):62–158. doi: 10.1124/pharmrev.122.000618McKenna F, McLaughlin PJ, Lewis BJ, Sibbring GC, Cummerson JA, Bowen-Jones D, Moots RJ. Dopamine receptor expression on human T- and B-lymphocytes, monocytes, neutrophils, eosinophils and NK cells: a flow cytometric study. J Neuroimmunol. 2002;132(1– 2):34–40. doi: 10.1016/s0165-5728(02)00280-1McKenna F, McLaughlin PJ, Lewis BJ, Sibbring GC, Cummerson JA, Bowen-Jones D, Moots RJ. Dopamine receptor expression on human T- and B-lymphocytes, monocytes, neutrophils, eosinophils and NK cells: a flow cytometric study. J Neuroimmunol. 2002;132(1– 2):34–40. doi: 10.1016/s0165-5728(02)00280-1Pacheco R. Targeting dopamine receptor D3 signalling in inflammation. Oncotarget. 2017;8(5):7224– 7225. doi: 10.18632/oncotarget.14601Pacheco R. Targeting dopamine receptor D3 signalling in inflammation. Oncotarget. 2017;8(5):7224– 7225. doi: 10.18632/oncotarget.14601Elgueta D, Aymerich MS, Contreras F, Montoya A, Celorrio M, Rojo-Bustamante E, Riquelme E, González H, Vásquez M, Franco R, Pacheco R. Pharmacologic antagonism of dopamine receptor D3 attenuates neurodegeneration and motor impairment in a mouse model of Parkinson’s disease. Neuropharmacology. 2017;113(PtA):110–123. doi: 10.1016/j.neuropharm.2016.09.028Elgueta D, Aymerich MS, Contreras F, Montoya A, Celorrio M, Rojo-Bustamante E, Riquelme E, González H, Vásquez M, Franco R, Pacheco R. Pharmacologic antagonism of dopamine receptor D3 attenuates neurodegeneration and motor impairment in a mouse model of Parkinson’s disease. Neuropharmacology. 2017;113(PtA):110–123. doi: 10.1016/j.neuropharm.2016.09.028Hodo TW, Prudente de Aquino MT, Shimamoto A, Shanker A. Critical Neurotransmitters in the Neuroimmune Network. Front Immunol. 2020;11:1869. doi: 10.3389/fimmu.2020.01869Hodo TW, Prudente de Aquino MT, Shimamoto A, Shanker A. Critical Neurotransmitters in the Neuroimmune Network. Front Immunol. 2020;11:1869. doi: 10.3389/fimmu.2020.01869Vidal PM, Pacheco R.The Cross-Talk Between the Dopaminergic and the Immune System Involved in Schizophrenia. Front Pharmacol. 2020;11:394. doi: 10.3389/fphar.2020.00394Vidal PM, Pacheco R.The Cross-Talk Between the Dopaminergic and the Immune System Involved in Schizophrenia. Front Pharmacol. 2020;11:394. doi: 10.3389/fphar.2020.00394Brito-Melo GE, Nicolato R, de Oliveira AC, Menezes GB, Lélis FJ, Avelar RS, Sá J, Bauer ME, Souza BR, Teixeira AL, Reis HJ. Increase in dopaminergic, but not serotoninergic, receptors in T-cells as a marker for schizophrenia severity. J Psychiatr Res. 2012;46(6):738– 742. doi: 10.1016/j.jpsychires.2012.03.004Brito-Melo GE, Nicolato R, de Oliveira AC, Menezes GB, Lélis FJ, Avelar RS, Sá J, Bauer ME, Souza BR, Teixeira AL, Reis HJ. Increase in dopaminergic, but not serotoninergic, receptors in T-cells as a marker for schizophrenia severity. J Psychiatr Res. 2012;46(6):738– 742. doi: 10.1016/j.jpsychires.2012.03.004Boneberg EM, von Seydlitz E, Pröpster K, Watzl H, Rockstroh B, Illges H. D3 dopamine receptor mRNA is elevated in T cells of schizophrenic patients whereas D4 dopamine receptor mRNA is reduced in CD4 + -T cells. J Neuroimmunol. 2006;173(1–2):180–187. doi: 10.1016/j.jneuroim.2005.11.018Boneberg EM, von Seydlitz E, Pröpster K, Watzl H, Rockstroh B, Illges H. D3 dopamine receptor mRNA is elevated in T cells of schizophrenic patients whereas D4 dopamine receptor mRNA is reduced in CD4 + -T cells. J Neuroimmunol. 2006;173(1–2):180–187. doi: 10.1016/j.jneuroim.2005.11.018Mancini M, Natoli S, Gardoni F, Di Luca M, Pisani A. Dopamine Transmission Imbalance in Neuroinflammation: Perspectives on Long-Term COVID-19. Int J Mol Sci . 2023;24(6):5618. doi: 10.3390/ijms24065618Mancini M, Natoli S, Gardoni F, Di Luca M, Pisani A. Dopamine Transmission Imbalance in Neuroinflammation: Perspectives on Long-Term COVID-19. Int J Mol Sci . 2023;24(6):5618. doi: 10.3390/ijms24065618Felger JC, Miller AH. Cytokine effects on the basal ganglia and dopamine function: The subcortical source of inflammatory malaise. Front. Neuroendocrinol . 2012;33:315–327. doi: 10.1016/j.yfrne.2012.09.003Felger JC, Miller AH. Cytokine effects on the basal ganglia and dopamine function: The subcortical source of inflammatory malaise. Front. Neuroendocrinol . 2012;33:315–327. doi: 10.1016/j.yfrne.2012.09.003Quintero-Villegas A, Valdés-Ferrer SI. Role of 5-HT receptors in the immune system in health and disease. Mol Med. 2019;26(1):2. doi: 10.1186/s10020-019-0126-xQuintero-Villegas A, Valdés-Ferrer SI. Role of 5-HT receptors in the immune system in health and disease. Mol Med. 2019;26(1):2. doi: 10.1186/s10020-019-0126-xKrabbe G, Matyash V, Pannasch U, Mamer L, Boddeke HW, Kettenmann H. Activation of serotonin receptors promotes microglial injury-induced motility but attenuates phagocytic activity. Brain Behav Immun . 2012;26(3):419–428. doi: 10.1016/j.bbi.2011.12.002Krabbe G, Matyash V, Pannasch U, Mamer L, Boddeke HW, Kettenmann H. Activation of serotonin receptors promotes microglial injury-induced motility but attenuates phagocytic activity. Brain Behav Immun . 2012;26(3):419–428. doi: 10.1016/j.bbi.2011.12.002Mahé C, Loetscher E, Dev KK, Bobirnac I, Otten U, Schoeffter P. Serotonin 5-HT7 receptors coupled to induction of interleukin-6 in human microglial MC-3 cells. Neuropharmacology. 2005;49(1):40–47. doi: 10.1016/j.neuropharm.2005.01.025Mahé C, Loetscher E, Dev KK, Bobirnac I, Otten U, Schoeffter P. Serotonin 5-HT7 receptors coupled to induction of interleukin-6 in human microglial MC-3 cells. Neuropharmacology. 2005;49(1):40–47. doi: 10.1016/j.neuropharm.2005.01.025Turkin A, Tuchina O, Klempin F. Microglia Function on Precursor Cells in the Adult Hippocampus and Their Responsiveness to Serotonin Signaling. Front Cell Dev Biol. 2021;9:665739. doi: 10.3389/fcell.2021.665739Turkin A, Tuchina O, Klempin F. Microglia Function on Precursor Cells in the Adult Hippocampus and Their Responsiveness to Serotonin Signaling. Front Cell Dev Biol. 2021;9:665739. doi: 10.3389/fcell.2021.665739

The authors declare that there are no conflicts of interest present.