Rudnitskaya Ekaterina A, Kozlova Tatiana A, Burnyasheva Alena O, Stefanova Natalia A, Kolosova Nataliya G
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), 10 Lavrentyeva Ave., 630090 Novosibirsk, Russia.
Biomedicines. 2021 Jul 15;9(7):823. doi: 10.3390/biomedicines9070823.
Sporadic Alzheimer's disease (AD) is a severe disorder of unknown etiology with no definite time frame of onset. Recent studies suggest that middle age is a critical period for the relevant pathological processes of AD. Nonetheless, sufficient data have accumulated supporting the hypothesis of "neurodevelopmental origin of neurodegenerative disorders": prerequisites for neurodegeneration may occur during early brain development. Therefore, we investigated the development of the most AD-affected brain structures (hippocampus and prefrontal cortex) using an immunohistochemical approach in senescence-accelerated OXYS rats, which are considered a suitable model of the most common-sporadic-type of AD. We noticed an additional peak of neurogenesis, which coincides in time with the peak of apoptosis in the hippocampus of OXYS rats on postnatal day three. Besides, we showed signs of delayed migration of neurons to the prefrontal cortex as well as disturbances in astrocytic and microglial support of the hippocampus and prefrontal cortex during the first postnatal week. Altogether, our results point to dysmaturation during early development of the brain-especially insufficient glial support-as a possible "first hit" leading to neurodegenerative processes and AD pathology manifestation later in life.
散发性阿尔茨海默病（AD）是一种病因不明的严重疾病，发病时间无明确界定。近期研究表明中年是AD相关病理过程的关键时期。尽管如此，已有足够的数据支持“神经退行性疾病的神经发育起源”这一假说：神经退行性变的先决条件可能在大脑早期发育过程中出现。因此，我们采用免疫组化方法，在衰老加速的OXYS大鼠中研究了AD影响最严重的脑结构（海马体和前额叶皮质）的发育情况，OXYS大鼠被认为是最常见的散发性AD类型的合适模型。我们注意到在出生后第三天，OXYS大鼠海马体中神经发生出现了一个额外的峰值，且与凋亡峰值时间吻合。此外，我们还发现，在出生后的第一周，神经元向前额叶皮质迁移延迟，海马体和前额叶皮质的星形胶质细胞和小胶质细胞支持出现紊乱。总之，我们的研究结果表明，大脑早期发育过程中的发育不成熟，尤其是胶质细胞支持不足，可能是导致神经退行性变过程和晚年AD病理表现的“首次打击”。
