Прогениторы олигодендроцитов при шизофрении: патогенетическая роль и потенциальная мишень для терапии

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.

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