Repeat exposure to heat is known to contribute to increased risk for cardiovascular and neurodegenerative diseases. This repeat exposure to heat can lead to chronic heat stress (HS), defined as an internal body temperature of 40°C, but less than 41°C. The effects of chronic HS have been well documented, but the mechanisms by which HS induces neurodegeneration remain unclear. We hypothesize that neurodegeneration induced by HS is mediated by neuroinflammation and accelerates the aging phenotype. 52-week-old (aged) or 25-week old (young) C57BL/6J male and female mice were exposed to 40°C at 50% humidity for 3 hours a day, 3 days a week, for 3 weeks. Animals were euthanized for tissue collection one week following the final heat stress exposure. The prefrontal cortex and brainstem were used for RT-qPCR to examine differential gene expression in HS mice compared to non-HS mice. In aged mice, Ngf expression trended lower in HS mice compared to the non-HS mice (0.42 ± 0.13 fold compared to non-HS, p = 0.0665, n=2-4/group respectively). Trkb expression in HS mice also trended lower than non-HS mice (0.57 ± 0.09 fold, p = 0.0668) in aged mice. In young mice, neither Ngf (1.46 ± 0.16 fold compared to non-HS, p = 0.2622, n = 3-6/group) not Bdnf (1.05 ± 0.17 fold, p = 0.6684) differed. In addition to RT-qPCR, single nucleus RNA sequencing was utilized to determine genes of interest that may mediate HS-induced neurodegeneration. There were 109 genes in oligodendrocytes that were significantly downregulated in HS mice including Meox2 and Pilrb2. In addition, 264 genes in oligodendrocytes were upregulated in HS mice such as plehka4. These genes are prime targets for further study to determine their potential role in HS-induced neurodegeneration. We also evaluated the presence and activation of microglia in the hypothalamus of both aged and young mice exposed to HS through immunofluorescence staining with Iba4. Preliminary results indicate a robust activation and proliferation of microglia in the hypothalamus of both young and old HS mice compared to non-HS controls. These data support the hypothesis that chronic HS promotes neurodegeneration and inflammatory phenotypes in aged mice, while younger mice do not exhibit a strong neuronal gene expression response to HS. Both young and aged mice display neuronal immune involvement through increased microglia activation following repeat exposure to heat stress. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Brown et al. (Fri,) studied this question.