PDF(Pubmed)
Abstract：
Heat stress exposure in intermittent heat waves and subsequent exposure during war theaters pose 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 transcriptome profile showed heat stress-induced altered acute phase response pathways, causing neural, hepatic, and systemic inflammation and impaired synaptic plasticity. Results also demonstrated that proinflammatory molecules such as 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. Furthermore, current research identified Orosomucoid 2 (ORM2) in the liver as one of the mediators of the liver-brain axis due to heat exposure. In conclusion, the transcriptome profiling in elderly heat-stressed mice revealed a coordinated network of liver-brain axis pathways with increased hepatic ORM2 secretion, possibly due to gut inflammation and dysbiosis. The above secretion of ORM2 may impact the brain through a leaky blood-brain barrier, thus emphasizing intricate multi-organ crosstalk.
摘要：
间歇性热浪中的热应激暴露以及随后在战区中的暴露构成了临床挑战，可能导致老年人的多器官功能障碍和长期并发症。使用老年小鼠模型和高通量测序，这项研究调查了热应激暴露期间肝脑连接的分子动力学。周期性热应激诱导的独特基因表达模式出现在脑和肝组织中。改变的转录组特征显示热应激诱导的急性期反应途径改变，导致神经，肝，全身炎症和突触可塑性受损。结果还表明，促炎分子如S100B，IL-17、IL-33和神经系统疾病信号通路上调，而保护性途径如芳香烃受体信号被下调。并行,Rantes,IRF7、NOD1/2、TREM1和肝损伤信号通路上调。此外，当前的研究确定肝脏中的Orosomucoid2（ORM2）是由于热暴露引起的肝脑轴介质之一。总之,老年热应激小鼠的转录组分析揭示了肝脑轴通路与肝脏ORM2分泌增加的协调网络，可能是由于肠道炎症和生态失调。ORM2的上述分泌可能通过渗漏的血脑屏障影响大脑，从而强调复杂的多器官串扰。
