句号(音乐)
多巴胺
神经科学
多巴胺受体
睡眠(系统调用)
心理学
医学
内科学
物理
计算机科学
声学
操作系统
作者
Yuichi Makino,Nathaniel Hodgson,Emma Doenier,Anna Victoria Serbin,K Osada,Pietro Artoni,Matthew Dickey,Breanna Sullivan,Amelia Potter-Dickey,Jelena Komanchuk,Bikram Sekhon,Nicole Létourneau,Neal D. Ryan,Jeanette M. Trauth,Judy L. Cameron,Takao K. Hensch
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2024-10-09
卷期号:16 (768)
标识
DOI:10.1126/scitranslmed.adh9763
摘要
Early life stress (ELS) yields cognitive impairments of unknown molecular and physiological origin. We found that fragmented maternal care of mice during a neonatal critical period from postnatal days P2-9 elevated dopamine receptor D2R and suppressed D4R expression, specifically within the anterior cingulate cortex (ACC) in only the male offspring. This was associated with poor performance on a two-choice visual attention task, which was acutely rescued in adulthood by local or systemic pharmacological rebalancing of D2R/D4R activity. Furthermore, ELS male mice demonstrated heightened hypothalamic orexin and persistently disrupted sleep. Given that acute sleep deprivation in normally reared male mice mimicked the ACC dopamine receptor subtype modulation and disrupted attention of ELS mice, sleep loss likely underlies cognitive deficits in ELS mice. Likewise, sleep impairment mediated the attention deficits associated with early adversity in human children, as demonstrated by path analysis on data collected with multiple questionnaires for a large child cohort. A deeper understanding of the sex-specific cognitive consequences of ELS thus has the potential to reveal therapeutic strategies for overcoming them.
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