Heat Acclimation Regulates the Autophagy-Lysosome Function to Protect Against Heat Stroke-Induced Brain Injury in Mice

Abstract

Background/Aims: The mechanisms underlying the protective role of heat acclimation (HA) in heat stroke (HS)-induced brain injury are still unclear. The autophagy-lysosome pathway is known to pay an important role in protecting stressed or diseased cells from death. Nevertheless, whether autophagy and lysosomes are involved in HA-mediated neuroprotection following HS exposure remains unclear. Methods: The protective effects of HA were assessed by rectal temperature, hematoxylin-eosin staining, transmission electron microscopic analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining, and Fluoro Jade B staining, after mice were subjected to HS. The effects of HA on autophagy and lysosomes were assessed in the presence of the autophagy inhibitor 3-methyladenine (3MA). Autophagy and lysosome-associated proteins were analysed by Western blotting. Results: We found that HA protected against HS-induced death and brain injury. HS can robustly induce autophagy and impair lysosome function. HA pre-conditioning significantly modulated the autophagy level, and improved lysosome function in HS mice. Furthermore, 3MA completely abolished the neuroprotective effect of HA on HS. Conclusion: HS may induce brain injury through lysosomal dysfunction and impaired autophagic flux. HA protected against HS-induced brain injury via a mechanism involving the autophagy-lysosome pathway.

Homocysteine exaggerates microglia activation and neuroinflammation through microglia localized STAT3 overactivation following ischemic stroke

“…Fluoro-Jade B is a high affinity fluorescent marker for the localization of neuronal degeneration. Fluoro-Jade B staining was performed using a modification of a previously published procedure [ 15 ]. Briefly, the sections were immersed in a solution containing 1% sodium hydroxide in 80% alcohol for 5 min, followed by 2 min in 70% alcohol and 2 min in distilled water.…”

TREM2 Regulates Heat Acclimation-Induced Microglial M2 Polarization Involving the PI3K-Akt Pathway Following EMF Exposure

“…Heat acclimation (HA) is thought to be able to enhance innate cytoprotective pathways against novel stressors via cross-tolerance mechanisms (Horowitz, 2017). HA provides neuroprotection against a variety of stressors, including heatstroke (Yi et al, 2017), hyperoxia (Arieli et al, 2003), and traumatic brain injury (Shein et al, 2008). To date, these effects have not yet been studied in response to EMF exposure; however, similar beneficial roles are hypothesized.…”

The Relationship Between Autophagy and Brain Plasticity in Neurological Diseases

“…Its protective effect might be related to the decrease of apoptosis and the recovery of autophagy flux in the cortex area of rat brain (Cui et al, 2017). HS (heat stroke) can lead to brain injury via impaired autophagy flux and lysosomal dysfunction, and HA (heat acclimation) has a protective exerts neuroprotection on HS-induced brain injury through the mechanism of autophagy - lysosomal pathway (Yi et al, 2017).…”