Glutamate metabolizing enzymes in frontal, cingulate and cerebellar cortex: anomalities revealed in schizophrenia

Aim: to compare distributions of glutamine synthetase (GS) and glutamate dehydrogenase (GDH) activities and amounts of their immunoreactive forms amongst frontal, anterior, posterior cingulate, and cerebellar cortices in schizophrenia cases and controls. Material and methods: group of patients with schizophrenia: 4 men and 4 women (36–80 years old) diagnosed according ICD-10 (F20.00, F20.02, F20.31, and F20.50 — 3, 3, 1 and 1 patient). Control group: 8 men and 1 woman (29–79 years old). No significant between-group differences were found in age and postmortem interval (p > 0,05). Non-parametric statistics was used. Results: no signifcant between-group difference was observed in GS activity in investigated brain structures (p > 0,05). Following differences were found in schizophrenia compared with controls: amount of immunoreactive GS was decreased in frontal cortex (p < 0,001), it was increased in posterior cingulate cortex and cerebellum (p < 0,001 and p < 0,004), but unchanged in anterior cingulate cortex, whereas level of GS-like protein (GSLP) was signifcantly elevated in all four brain structures (р < 0,004, р < 0,02, р < 0,04, and р < 0,001). When compared with controls, schizophrenia cases displayed elevated GDH activity in frontal, posterior cingulate cortex and cerebellum (p < 0,004, p < 0,05, and p < 0,002), but unchanged in anterior cingulate cortex. When compared with control, following differences were found in schizophrenia: elevation in levels of immunoreactive GDHI, GDHII, and GDHIII in frontal cortex (р < 0,008, р < 0,003, and р < 0,001); elevation in levels of immunoreactive GDHI, GDHII, and GDHIII in posterior cingulate cortex (р < 0,004, р < 0,001, and р < 0,02); elevation in levels of immunoreactive GDHII and GDHIII in cerebellum (р < 0,02 and р < 0,001). No between-group differences in levels of immunoreactive GDH forms were found in anterior cingulate cortex. Conclusion: alteration in levels of GS, GSLP, and GDH forms in brain of patients with schizophrenia is one of causes of glutamate metabolism disturbances in these brain structures and an important aspect of schizophrenia pathogenesis.

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