Abstract：
Prolonged confinement in cramped spaces can lead to derangements in brain function/structure, yet the underlying mechanisms remain unclear. To investigate, we subjected mice to restraint stress to simulate long-term narrow and enclosed space confinement, assessing their mental state through behavioral tests. Stressed mice showed reduced center travel and dwell time in the Open Field Test and increased immobility in the Tail Suspension Test. We measured lower hippocampal brain-derived neurotrophic factor levels and cortical monoamine neurotransmitters (5-HT and NE) in the stressed group. Further examination of the body\'s immune levels and serum metabolism revealed immune dysregulation and metabolic imbalance in the stressed group. The results of the metabolic network regulation analysis indicate that the targets affected by these differential metabolites are involved in several metabolic pathways that the metabolites themselves participate in, such as the \"long-term depression\" and \"purine metabolism\" pathways. Additionally, these targets are also associated with numerous immune-related pathways, such as the TNF, NF-κB, and IL-17 signaling pathways, and these findings were validated using GEO dataset analysis. Molecular docking results suggest that differential metabolites may regulate specific immune factors such as TNF-α, IL-1β, and IL-6, and these results were confirmed in experiments. Our research findings suggest that long-term exposure to confined and narrow spaces can lead to the development of psychopathologies, possibly mediated by immune system dysregulation and metabolic disruption.
摘要：
长时间限制在狭窄的空间会导致大脑功能/结构紊乱，然而，潜在的机制仍不清楚。为了调查，我们对小鼠进行约束应激，以模拟长期狭窄和封闭的空间限制，通过行为测试评估他们的精神状态。应激小鼠在开放场测试中显示出减少的中心行程和停留时间,并且在尾部悬吊测试中显示出增加的不动性。我们在应激组中测量了较低的海马脑源性神经营养因子水平和皮质单胺类神经递质（5-HT和NE）。进一步检查机体的免疫水平和血清代谢，发现应激组的免疫失调和代谢失衡。代谢网络调控分析的结果表明，受这些差异代谢物影响的靶标参与了代谢物本身参与的几种代谢途径，如“长期抑郁”和“嘌呤代谢”途径。此外,这些目标也与许多免疫相关的途径有关，比如TNF，NF-κB,和IL-17信号通路，并使用GEO数据集分析验证了这些发现。分子对接结果提示差异代谢产物可能调控特异性免疫因子如TNF-α,IL-1β,和IL-6，这些结果在实验中得到证实。我们的研究结果表明，长期暴露在狭窄和狭窄的空间会导致精神病理学的发展，可能由免疫系统失调和代谢破坏介导。
