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. 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.