Differential Cerebellar Hsp70 Expression Across Estrous Phases in Mice Exposed to Exertional Heat Stroke

Exertional heat stroke (EHS), the most severe manifestation of heat-related illness, is characterized by severe hyperthermia leading to long-term central nervous system (CNS) dysfunction. EHS-induced CNS damage can lead to long-term neurological impairment or death. Heat shock protein (HSP), particularly HSP70, play a central cytoprotective role during thermal, inflammatory, and oxidative stress. Previous work from our group shows estrous phase-dependent differences in EHS susceptibility, with female mice in estrus (E) running longer than in diestrus (D) while presenting a higher mortality rate. Given the cerebellum’s vulnerability to EHS, we investigated whether cerebellar HSP70 expression differs between E and D following EHS and whether reduced expression contributes to mortality. Methods: HSP70 expression was quantified in cerebellar tissue at 30 min, 3 h, and 24 h post-EHS and in non-surviving estrus animals (E-NS) using Western blot analysis. Results: At 3h post-collapse, HSP70 expression was significantly higher in D compared with E (27.7%, p = 0.02). No group differences were observed at 24h. Notably, E-NS animals exhibited lower HSP70 expression than E survivors (19.1%, p = 0.02). Conclusion: Early (< 3h) induction of cerebellar HSP70 appears to confer protection following EHS, and inadequate HSP70 upregulation during estrus may contribute to increased mortality in this phase of the cycle. Funding: DoD. USAMRAA. HT9425-23-PRMRP-FPA Grant log number BA220322 to OL. 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.