Cai Yiming, Zhao Ruofan, Huang Yuxuan, Yang Huiping, Liu Ye, Yang Rui, Zhang Xiangyu, Liu Yiran, Yan Shu, Liu Xiaoyu, Liu Xiao, Yin Xueyong, Yu Yang, Gao Shuai, Li Yating, Zhao Ye, Shi Haishui
Neuroscience Research Center, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China.
Nursing School, Hebei Medical University, Shijiazhuang 050031, China.
Pharmacol Biochem Behav. 2024 Dec;245:173913. doi: 10.1016/j.pbb.2024.173913. Epub 2024 Nov 23.
Previous studies have demonstrated that early life stress (ELS) impacts hoarding behavior in adult humans. This study aimed to assess the potential mitigation by environmental enrichment on hoarding behavior in rodents caused by maternal separation, thereby providing insights into therapeutic strategies for hoarding disorder.
Newborn mice were randomly divided into four groups. The control group was allowed to grow naturally. The maternal separation group underwent two weeks of maternal separation. The short-term environmental enrichment group received two weeks of environmental enrichment intervention after the two weeks of maternal separation. The long-term environmental enrichment group received five weeks of environmental enrichment intervention after the two weeks of maternal separation. Hoarding behavior was assessed during adolescence and adulthood. Hippocampal tissue from adult female mice was analyzed using LC-MS/MS-based metabolomics. Spearman correlation analysis was then performed to assess the relationship between differentially expressed metabolites and hoarding behavior.
Environmental enrichment attenuates maternal separation-induced excessive hoarding behavior in adult female mice. The untargeted metabolomics of the hippocampal region in female mice showed that long-term environmental enrichment reversed multiple differential metabolites, including Substance P, which were mainly concentrated in metabolic pathways such as cancer choline metabolism, glycolipid metabolism, and linoleic acid metabolism.
Our findings indicate that ELS and long-term environmental enrichment have sex-dependent effects on adult hoarding behavior, potentially related to altered hippocampal metabolism. This study highlights the importance of environmental enrichment in mitigating the long-term effects of early maternal separation on hoarding behavior.
先前的研究表明,早期生活压力(ELS)会影响成年人类的囤积行为。本研究旨在评估环境富集对母鼠分离引起的啮齿动物囤积行为的潜在缓解作用,从而为囤积障碍的治疗策略提供见解。
将新生小鼠随机分为四组。对照组自然生长。母鼠分离组经历两周的母鼠分离。短期环境富集组在母鼠分离两周后接受两周的环境富集干预。长期环境富集组在母鼠分离两周后接受五周的环境富集干预。在青春期和成年期评估囤积行为。使用基于液相色谱-质谱联用(LC-MS/MS)的代谢组学分析成年雌性小鼠的海马组织。然后进行Spearman相关性分析,以评估差异表达代谢物与囤积行为之间的关系。
环境富集减轻了成年雌性小鼠中母鼠分离诱导的过度囤积行为。雌性小鼠海马区的非靶向代谢组学表明,长期环境富集逆转了多种差异代谢物,包括P物质,这些代谢物主要集中在癌症胆碱代谢、糖脂代谢和亚油酸代谢等代谢途径中。
我们的研究结果表明,ELS和长期环境富集对成年囤积行为有性别依赖性影响,可能与海马代谢改变有关。本研究强调了环境富集在减轻早期母鼠分离对囤积行为的长期影响方面的重要性。