Translational Medicine Immunology Laboratory, Clinical Research Center, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian Province, China.
Queen Mary School of Nanchang University, Nanchang, 330031, Jiangxi Province, China.
Mol Neurobiol. 2024 May;61(5):3019-3030. doi: 10.1007/s12035-023-03742-9. Epub 2023 Nov 14.
Sociability stands as a crucial factor in the evolutionary success of all mammalian species. Notably, enriched environment (EE) housing has been shown to enhance sociability in mice. However, the precise underlying molecular mechanism remains elusive. In this study, we established an EE paradigm, housing mice for a 14-day period. Both enhanced sociability and an increased spine density in the medial prefrontal cortex (mPFC) of mice subjected to EE were detected. To elucidate the potential molecular pathway, we conducted high-performance liquid chromatography tandem mass spectrometry (HPLC-MS) analysis of the entire mPFC from both EE and home-caged (HC) housed mice. Our analysis identified 16 upregulated and 20 downregulated proteins in the EE group. Among them, Extended Synaptotagmin 1 (ESyt1), an activity-dependent endoplasmic reticulum (ER)-plasma membrane (PM) tethering protein associated with synaptic function and growth, emerged as a potentially key player in the increased synapse formation and enhanced sociability observed in EE-housed mice. Further investigation, involving the knockdown of ESyt1 expression via sh ESyt1 lentivirus in the mPFC, revealed that ESyt1 is crucial for increased spine density of mPFC and enhanced sociability of mice in an enriched environment but not in normal condition. Overall, our findings uncover a novel mechanistic insight into the positive influence of environmental enrichment on social behavior via ESyt1-mediated pathways.
社交能力是所有哺乳动物物种在进化上取得成功的关键因素。值得注意的是，丰富环境（EE）饲养已被证明可以提高小鼠的社交能力。然而，确切的潜在分子机制仍然难以捉摸。在这项研究中，我们建立了一个 EE 范式，让老鼠饲养 14 天。我们发现，接受 EE 处理的老鼠表现出增强的社交能力和内侧前额叶皮层（mPFC）中树突棘密度的增加。为了阐明潜在的分子途径，我们对 EE 和常规饲养（HC）老鼠的整个 mPFC 进行了高效液相色谱串联质谱（HPLC-MS）分析。我们的分析确定了 EE 组中 16 种上调和 20 种下调的蛋白质。其中，延伸突触结合蛋白 1（ESyt1）是一种与突触功能和生长相关的、依赖于活动的内质网（ER）-质膜（PM）连接蛋白，作为 EE 饲养的老鼠中观察到的突触形成增加和社交能力增强的潜在关键因素出现。进一步的研究，包括通过 mPFC 中的 sh ESyt1 慢病毒敲低 ESyt1 的表达，表明 ESyt1 对于增加 mPFC 的树突棘密度和增强在丰富环境中的老鼠的社交能力是至关重要的，但在正常条件下则不是。总的来说，我们的发现揭示了一个通过 ESyt1 介导的途径对社交行为的积极影响的新的机制见解。
