Exertional heat stroke leads to concurrent long‐term epigenetic memory, immunosuppression and altered heat shock response in female mice

Abstract

Exposure to exertional heat stroke (EHS) has been linked to increased long-term decrements of health. Epigenetic reprogramming is involved in the response to heat acclimation; however, whether the long-term effects of EHS are mediated by epigenetic reprogramming is unknown. r In female mice, we observed DNA methylation reprogramming in bone marrow-derived (BMD) monocytes as early as 4 days of recovery from EHS and as late as 30 days compared with sham exercise controls. r Whole blood, collected after 30 days of recovery from EHS, exhibited an immunosuppressive phenotype when challenged in vitro by lipopolysaccharide. r After 30 days of recovery from EHS, BMD monocytes exhibited an altered in vitro heat shock response. r The location of differentially methylated CpGs are predictive of both the immunosuppressive phenotype and altered heat shock responses.

Do exertional heat stroke and environmental heat involve epigenetic memory?

“…Collectively, the data presented by Murray et al . (2021) support the hypothesis that EHS induced long‐term molecular changes that may be associated with an altered epigenetic profile. In addition to the methylome changes in bone marrow cells per se , these cells interact with other systems, including brain areas that affect behavioural or physiological responses, e.g.…”

“…Before the report in this issue of The Journal of Physiology by Murray et al . (2021), the only evidence on the epigenetic‐heat stress relationship in adults was our work on heat acclimation memory (Tetievsky & Horowitz, 2010; Tetievsky et al . 2014) and the Schnermann et al .…”

“…The investigation by Murray et al . (2021) is the first study using an animal EHS (exertional heat stroke) model, investigating whether epigenetic mechanisms are involved with consistent changes produced by exertional heat stroke.…”

Incidence of Recurrent Exertional Heat Stroke in a Warm-Weather Road Race

“…When considering biochemical recovery, recent data have demonstrated elevated markers up to 16 days post-EHS based on aggregated consensus of normal values [ 31 ]. Additionally, an altered heat shock response has been noted at 30 days post-EHS in a mouse model [ 32 ], though neither study examined future exposure or the occurrence of future EHS episodes.…”

Immunosuppression is associated with epigenetic remodelling in a murine model of exertional heat stroke

“…But repeating this research in male mice is important, as their epigenome may be modified from EHS, despite not developing the same metabolic disorder (Murray et al . 2021).…”