Heat therapy increases brain HSP70 and BDNF content in male mice

Heat shock proteins (HSPs) are molecular chaperones that play important roles in protein homeostasis, with HSP70 linked to a role in neuroprotection. HSP70 is upregulated in response to various stressors, such as heat therapy (HT), which has been shown to increase brain-derived neurotrophic factor (BDNF) content. BDNF reduces the activity of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), the rate-limiting enzyme responsible for the generation of amyloid-β (Aβ) peptides that form the characteristic Aβ plaques observed in Alzheimer's disease brains. The current pilot study examined whether 4 wk of HT can increase HSP70 and BDNF content (pro and mature forms) in the brain, and alter markers of amyloid precursor protein (APP) processing. Male mice had their core temperature maintained between 37.0 and 38.0°C in Control (CON, <i>n</i> = 16) and 40.5 and 41.5°C in Heat Therapy (HT, <i>n</i> = 16) for 20 min every 72 h over 4 wk. Seventy-two hours after the last treatment, the prefrontal cortex (PFC) and hippocampus (HIP) were collected. HT significantly increased HSP70 levels in both the hippocampus and prefrontal cortex compared with controls (<i>P</i> = 0.0007, PFC CON = 1.001 [0.314], PFC HT = 1.546 [0.948], HIP CON = 1.000 [0.356], HIP HT = 2.207 [0.756]). In the HIP, proBDNF levels were also higher in the HT group relative to both the control group and the PFC (<i>P</i> < 0.05, PFC CON = 1.000 [0.156], PFC HT = 0.984 [0.607], HIP CON = 1.001 [0.242], HIP HT = 1.575 [0.482]. There were no differences in mature BDNF in either PFC or HIP regions (<i>P</i> > 0.05, PFC CON = 1.000 [0.273], PFC HT = 1.174 [0.266], HIP CON = 0.999 [0.130], HIP HT = 0.971 [0.207]), The findings from our pilot study suggest that HT enhances the expression of HSP70 and BDNF, indicating the potential to modulate key neuroprotective proteins. Future studies in dedicated preclinical mouse models of Alzheimer's disease using the heat therapy regimen are warranted.<b>NEW & NOTEWORTHY</b> Four weeks of heat therapy increases heat shock protein (HSP)70 and brain-derived neurotrophic factor (BDNF) levels in the hippocampus and prefrontal cortex of mice, regions crucial for memory and cognition. These findings highlight the promise of heat therapy as a nonpharmacological strategy to enhance brain resilience against neurodegenerative diseases.