ГАМК, дефициты нейротрансмиттера глутамата при аутизме и их нейтрализация как новая гипотеза эффективной стратегии лечения

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Аннотация

Расстройства аутистического спектра (РАС) — это нарушения психического развития, характеризующиеся снижением социального взаимодействия и повторяющимся поведением. Механизмы этиологии РАС все еще неизвестны; однако ГАМК-эргической системе уделяется большое внимание в связи с тем, что она обладает потенциалом терапевтической мишени. Основываясь на том факте, что у людей с аутизмом отмечена измененная экспрессия генов, сопутствующая нарушению гематоэнцефалического барьера (ГЭБ) и целостности кишечного барьера, повышенный уровень глутамата в крови и тромбоцитах пациентов с РАС может быть связан с меньшим количеством мозжечковых ГАМК-ергических нейронов, менее активными ГАМК-синтезирующими ферментами и сниженным уровнем ГАМК в мозге. Эксайтотоксичные уровни высвобождения глутамата запускают каскад разрушительных клеточных событий, приводящих к отсроченной гибели нейронов. В соответствии с нашим пониманием эксайтотоксичности глутамата добавки ГАМК теоретически могут быть полезны при лечении определенных фенотипов аутизма. Хотя эффективных и безопасных препаратов, предотвращающих вызванные глутаматом повреждение и гибель клеток, до сих пор не существует, мы надеемся, что благодаря совместным усилиям нам удастся разработать лучшие варианты лечения. В данной статье автор выдвинула гипотезу о том, что использование интегрированной стратегии лечения с применением добавок ГАМК, регуляцией уровня хлорида (Cl-) и магния (Mg2+), добавками витамина D, пробиотиков для усиления экспрессии рецепторов ГАМК-А и глутаматдекарбоксилазы (GAD), а также мемантина для активации транспортеров глутамата и ингибирования NMDA рецепторов, может привести к снижению уровней глутамата, поддержать функционирование рецепторов ГАМК и тем самым воздействовать на повторяющееся поведение, нарушения социального взаимодействия и судорожные при- падки у людей с аутизмом.

Общая информация

Ключевые слова: аутизм, эксайтотоксичность глутамата, гамма-аминомасляная кислота, витамин Д, кишечная микробиота

Рубрика издания: Исследования и диагностика РАС

DOI: https://doi.org/10.17759/autdd.2020180306

Финансирование. Этот проект финансировался Национальной программой в области науки, технологий и инноваций (MAARIFAH), Город науки и технологии Короля Абдулазиза, номер гранта: 08-MED 510-02.

Благодарности. Автор благодарит деканат научных исследований и RSSU Университета короля Сауда за их техническую поддержку. Особая благодарность госпоже Рамеса Шафи Бхат, факультет биохимии, Колледж наук, КГУ за ее огромные усилия по улучшению рукописи.

Для цитаты: Эль-Ансари А. ГАМК, дефициты нейротрансмиттера глутамата при аутизме и их нейтрализация как новая гипотеза эффективной стратегии лечения // Аутизм и нарушения развития. 2020. Том 18. № 3. С. 46–63. DOI: 10.17759/autdd.2020180306

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Информация об авторах

Эль-Ансари Афаф, PhD, профессор Центральной лаборатории Женского центра научных и медицинских исследований, Университет короля Сауда, Совет по пищевой и экологической медицине, Центр исследований и терапии аутизмал, Эр-Рияд, Саудовская Аравия, ORCID: https://orcid.org/0000-0002-1404-5248, e-mail: afafkelansary@gmail.com

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