Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (ICG SB RAS), 10 Lavrentyeva Ave., Novosibirsk 630090, Russia.
Int J Mol Sci. 2023 Jan 11;24(2):1462. doi: 10.3390/ijms24021462.
It has been suggested that functional traits of the adult brain-all of which are established early in life-may affect the brain's susceptibility to Alzheimer's disease (AD). Results of our previous studies on senescence-accelerated OXYS rats, a model of sporadic AD, support this hypothesis. Here, to elucidate the molecular genetic nature of the aberrations revealed during brain maturation, we analyzed transcriptomes (RNA-seq data) of the prefrontal cortex (PFC) and hippocampus of OXYS rats and Wistar (control) rats in the period of brain maturation critical for OXYS rats (ages P3 and P10; P: postnatal day). We found more than 1000 differentially expressed genes in both brain structures; functional analysis indicated reduced efficiency of the formation of neuronal contacts, presumably explained mainly by deficits of mitochondrial functions. Next, we compared differentially expressed genes in the rat PFC and hippocampus from infancy to the progressive stage of AD-like pathology (five ages in total). Three genes (, , and ) showed overexpression in both brain regions of OXYS rats throughout the lifespan. Thus, reduced efficiency of the formation of neural networks in the brain of OXYS rats in infancy likely contributes to the development of their AD-like pathology.
有人认为，成年人大脑的功能特征——这些特征在生命早期就已确立——可能会影响大脑对阿尔茨海默病(AD)的易感性。我们之前对衰老加速 OXYS 大鼠(一种散发性 AD 模型)的研究结果支持这一假设。在这里，为了阐明在大脑成熟过程中发现的异常的分子遗传本质，我们分析了 OXYS 大鼠和 Wistar(对照)大鼠在大脑成熟关键期(P3 和 P10; P: 出生后第 3 天和第 10 天)的前额叶皮层(PFC)和海马体的转录组(RNA-seq 数据)。我们在这两个脑区发现了 1000 多个差异表达的基因;功能分析表明神经元接触形成的效率降低，这主要归因于线粒体功能的缺陷。接下来，我们比较了从婴儿期到 AD 样病理进展阶段(总共五个年龄)大鼠 PFC 和海马体中差异表达的基因。在 OXYS 大鼠的整个生命周期中，三个基因(、和)在两个脑区均过表达。因此，OXYS 大鼠在婴儿期大脑中神经网络形成效率的降低可能导致其 AD 样病理的发展。
