Periodic Heat Waves-induced neuronal etiology in the elderly is mediated by Gut-Liver-Brain axis: A Transcriptome Profiling Approach. Periodic Heat Waves-induced neuronal etiology in the elderly is mediated by Gut-Liver-Brain axis: A Transcriptome Profiling Approach

Heat stress exposure in intermittent heat waves and subsequent exposure during war theaters is a clinical challenge that can lead to multi-organ dysfunction and long-term complications in the elderly. Using an aged mouse model and high-throughput sequencing, this study investigated the molecular dynamics of the liver-brain connection during heat stress exposure. Distinctive gene expression patterns induced by periodic heat stress emerged in both brain and liver tissues. An altered transciptome showed heat stress-induced altered acute phase response pathways, causing neural, hepatic, and systemic inflammation, and impaired synaptic plasticity. Results also showed that proinflammatory molecules S100B, IL-17, IL-33 and neurological disease signaling pathways were upregulated, while protective pathways like aryl hydrocarbon receptor signaling were downregulated. In parallel, Rantes, IRF7, NOD1/2, TREM1, and hepatic injury signaling pathways were upregulated. Overall design: To study the underlying pathological changes in exposure to heat stress, an aging mouse model was used. Aged C57BL6/J (24 months old) mice were exposed to heat stress at 40± 0.5°C with a relative humidity of 60% ± 5% for three hours/day for 15 days mimicking a periodic heat wave exposure. The total number of animals in each group (n=3) was determined based on statistical power calculations to ensure adequate statistical analysis. The mice were randomly allocated to their respective cages following a randomization procedure. At 24 months and 16 days of age, all mice were euthanized, and serum and liver tissues were collected for further analysis.

间歇性热浪中的热应激暴露与战场环境下的后续热应激暴露，对老年群体而言是一项可引发多器官功能障碍与长期并发症的临床难题。本研究利用老年小鼠模型与高通量测序（high-throughput sequencing）技术，探究了热应激暴露过程中肝-脑轴（liver-brain connection）的分子动态变化。周期性热应激可在脑与肝脏组织中诱导出独特的基因表达模式。失调的转录组（transcriptome）显示，热应激可改变急性期反应通路（acute phase response pathways），进而引发神经、肝脏及全身性炎症，并损伤突触可塑性（synaptic plasticity）。研究结果同时表明，促炎分子S100B、IL-17、IL-33以及神经系统疾病信号通路均呈上调状态，而芳烃受体信号通路（aryl hydrocarbon receptor signaling）等保护性通路则呈现下调趋势。此外，Rantes、IRF7、NOD1/2、TREM1以及肝损伤信号通路均呈上调状态。实验整体设计：为探究热应激暴露相关的潜在病理变化，本研究采用老年小鼠模型。选取24月龄的老年C57BL6/J小鼠，将其置于温度为40±0.5℃、相对湿度60%±5%的环境中，每日暴露3小时，连续暴露15天，以模拟周期性热浪暴露。每组实验动物的数量（n=3）经统计效力计算确定，以保障后续统计分析的充分性。小鼠通过随机化程序分配至对应笼盒中。在小鼠达到24月龄16天时，对所有小鼠实施安乐死，并采集血清与肝脏组织用于后续分析。