Влияние мутантных генов APP и PSEN1 на асимметрию гиппокампа у мышей 5xFAD - трансгенной модели болезни Альцгеймера

Болезнь Альцгеймера (БА) – возрастная нейродегенеративная патология, а также одна из главных причин деменции с расстройством памяти и когнитивных функций. Важнейшую роль в процессе обучения и кодирования памяти играет зубчатая извилина гиппокампа (dentate gyrus, DG), которая подвергается существенным изменениям при БА. Для изучения механизмов, лежащих в основе БА, тестирования новых терапевтических средств создают модели этой патологии на мышах. Одной из наиболее популярных и актуальных моделей для исследования БА является трансгенная линия мышей 5xFAD c мутантными генами человека, а именно предшественника бета-амилоида (APP) и пресенилина-1 (PSEN1). Целью данной работы стало исследование влияния мутантных трансгенов APP и PSEN1 на микроструктуру DG гиппокампа у гетерозиготных самцов мышей трансгенной линии 5xFAD в возрасте 6 месяцев при помощи магнитно-резонансной томографии с диффузионно-тензорной визуализацией в сочетании с иммуногистохимическим анализом. Особый акцент был сделан и на оценке асимметрии гиппокампа, что ранее на мышах 5xFAD не исследовали. В DG гиппокампа обоих полушарий самцов мышей 5xFAD выявлены повышенное содержание бета-амилоида по сравнению с контрольной группой дикого типа в сочетании с более высокой плотностью микроглии, но отсутствие различий по уровню нейрогенеза. Наряду с этим обнаружена асимметрия гиппокампа у самцов мышей 5xFAD, проявляющаяся в увеличении объема правого гиппокампа и снижении уровня фракционной анизотропии в DG правого гиппокампа, а также в уменьшении плотности нейронов в DG с левой стороны по сравнению с диким типом. Исходя из полученных нами результатов, можно сделать заключение, что мутантные гены APP и PSEN1 человека вызывают изменение в DG гиппокампа, что может открыть новые возможности ранней диагностики болезни Альцгеймера. Выявленные нами изменения объема гиппокампа и его асимметрия могут стать важными биомаркерами, характеризующими данную патологию.

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