Enriched environment ameliorates neurobehavioral abnormalities, hippocampal inflammation, and synaptic dysfunction in adult male mice exposed to intermittent hypoxia during pregnancy

作者：Shi-Kun Fang, Fei Hu, Yu Zhang, Wei-Zhong Lun, Yueming Zhang, Xueyan Li, Kaixuan Zhang, Zhenyu Hu, Ru‐Meng Wei, Chongyang Ren, Gui-Hai Chen · 发表于：Brain Research Bulletin · 年份：2025 · DOI：10.1016/j.brainresbull.2025.111544 · 被引用次数：3 · 研究领域：Obstructive Sleep Apnea Research、Neuroscience of respiration and sleep、Neonatal and fetal brain pathology

BACKGROUND: Sleep apnea during gestation is marked by intermittent hypoxia (IH) and frequent arousals in humans. Prenatal exposure to IH (PIH) is believed to negatively impact the neurodevelopment of offspring born to women who experience sleep apnea during pregnancy. Research using rodent models has demonstrated that enriched environments (EE) can alleviate behavioral indicators of neuropsychiatric and cognitive impairments, potentially through modulation of inflammatory responses and synaptic mechanisms. However, the specific effects of EE on PIH-induced neurobehavioral alterations in adult animals, and the underlying biological mechanisms and potential correlations, remain largely unclear and warrant further investigation. METHODS: Pregnant C57BL/6J mice were exposed to IH or normoxic conditions during gestational days 15-21, after which their male offspring were housed in either enriched or standard environments from weaning through adulthood. anxiety-like behavior (ALB) was assessed using the Open Field Test (OFT) and Elevated Plus Maze (EPM), while depressive-like behavior (DLB) was measured through the Tail Suspension Test (TST) and Forced Swim Test (FST); memory and learning abilities were measured using the Morris Water Maze (MWM). Moreover, levels of hippocampal TNF-α, IL-6, and IL-1β were quantified using ELISA. Western blotting (WB) and RT-qPCR were employed to assess the protein and mRNA expression of NF-κB/NLRP3 pathway-related molecules, as well as GFAP, Iba1, ...