Heat therapy increases brain HSP-70 and BDNF content in male mice.

Abstract

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 weeks of HT can increase HSP70 and BDNF content (pro and mature forms) in the brain, as well as alter markers of amyloid precursor protein (APP) processing. Male mice had their core temperature maintained between 37.0-38.0° in Control (CON, n = 16) and 40.5-41.5° in Heat Therapy (HT, n = 16) for 20-minutes every 72 hours over 4-weeks. 72 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 to controls (p = 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 (p < 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 (p>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 heat therapy regimen are warranted.