德纳姆
海马结构
DNA甲基化
莫里斯水上航行任务
海马体
表观遗传学
甲基化
生物
神经科学
心理学
遗传学
基因
基因表达
作者
Priscila Chiavellini,Marianne Lehmann,Martina Canatelli-Mallat,Joseph A. Zoller,Claudia Beatriz Hereñú,Gustavo R. Morel,Steve Horvath,Rodolfo G. Goya
出处
期刊:The Journals of Gerontology
[Oxford University Press]
日期:2022-08-02
卷期号:77 (12): 2387-2394
被引量:10
标识
DOI:10.1093/gerona/glac153
摘要
Abstract In humans and rats, aging is associated with a progressive deterioration of spatial learning and memory. These functional alterations are correlated with morphological and molecular changes in the hippocampus. Here, we assessed age-related changes in DNA methylation (DNAm) landscape in the rat hippocampus and the correlation of spatial memory with hippocampal DNAm age in 2.6- and 26.6-month-old rats. Spatial memory performance was assessed with the Barnes maze test. To evaluate learning ability and spatial memory retention, we assessed the time spent by animals in goal sector 1 (GS1) and 3 (GS3) when the escape box was removed. The rat pan-tissue clock was applied to DNAm data from hippocampal tissue. An enrichment pathway analysis revealed that neuron fate commitment, brain development, and central nervous system development were processes whose underlying genes were enriched in hypermethylated CpGs in the old rats. In the old rat hippocampi, the methylation levels of CpG proximal to transcription factors associated with genes Pax5, Lbx1, Nr2f2, Hnf1b, Zic1, Zic4, Hoxd9; Hoxd10, Gli3, Gsx1 and Lmx1b, and Nipbl showed a significant regression with spatial memory performance. Regression analysis of different memory performance indices with hippocampal DNAm age was significant. These results suggest that age-related hypermethylation of transcription factors related to certain gene families, such as Zic and Gli, may play a causal role in the decline in spatial memory in old rats. Hippocampal DNAm age seems to be a reliable index of spatial memory performance in young and old rats.
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