Environmental enrichment attenuates maternal separation-induced excessive hoarding behavior in adult female mice

Yiming Cai; Ruofan Zhao; Yuxuan Huang; Huiping Yang; Ye Liu; Rui Yang; Xiangyu Zhang; Yiran Liu; Shu Yan; Xiaoyu Liu; Xiao Liu; Xueyong Yin; Yang Yu; Shuai Gao; Yating Li; Ye Zhao; Haishui Shi

doi:10.1016/j.pbb.2024.173913

Environmental enrichment attenuates maternal separation-induced excessive hoarding behavior in adult female mice

Pharmacol Biochem Behav. 2024 Nov 22:173913. doi: 10.1016/j.pbb.2024.173913. Online ahead of print.

Authors

Yiming Cai¹, Ruofan Zhao¹, Yuxuan Huang¹, Huiping Yang¹, Ye Liu¹, Rui Yang¹, Xiangyu Zhang¹, Yiran Liu¹, Shu Yan¹, Xiaoyu Liu¹, Xiao Liu¹, Xueyong Yin¹, Yang Yu¹, Shuai Gao¹, Yating Li², Ye Zhao³, Haishui Shi⁴

Affiliations

¹ Neuroscience Research Center, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China.
² Nursing School, Hebei Medical University, Shijiazhuang 050031, China.
³ Neuroscience Research Center, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key laboratory of Neurophysiology, Hebei Medicinal University, Shijiazhuang 050017, China. Electronic address: 19501828@hebmu.edu.cn.
⁴ Neuroscience Research Center, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China; Nursing School, Hebei Medical University, Shijiazhuang 050031, China; Hebei Key laboratory of Neurophysiology, Hebei Medicinal University, Shijiazhuang 050017, China; Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China. Electronic address: shihs@hebmu.edu.cn.

PMID: 39581387
DOI: 10.1016/j.pbb.2024.173913

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Environmental enrichment; Hippocampus metabolomics analysis; Hoarding behavior; Maternal separation.