Heat stroke induces autophagy as a protection mechanism against neurodegeneration in the brain.
Heat stroke (HS) is defined clinically as a condition when core body temperature rises above 40°C and is accompanied by central nervous system abnormalities. In this study, we established a rat model of HS by exposing anesthetized rats to elevated ambient temperature (40°C) until core temperature reaching 40.5°C (HS onset). The rat was immediately removed from heating chamber, allowed recovery for various time periods, and killed for histological and biochemical studies. Our results indicated neuronal shrinkage and pyknosis of the nucleus and sustained up to 12 h recovery time in cerebral cortex. Elevated expression of autophagy-related proteins, including microtubule associated protein light chain 3 and beclin 1 in cortical tissue at various times (3, 6, 12 h) of recovery was observed. In addition, the number of autophagosomes stained by monodansylcadaverine, a specific autophagosome marker, increased after heat exposure but was reduced by pretreatment with 3-methyladenine, an autophagy inhibitor. Furthermore, heat exposure increased neuronal degeneration in cortical tissue, as evidenced by staining with the fluorescent dye Fluoro-Jade B for degenerating neuron. Pretreatment with 3-methyladenine in HS rats aggravated neurodegeneration. Taken together, these results suggest that HS induces autophagy as a protection mechanism against neurodegeneration. Modulation of autophagy may provide a potential therapeutic approach for HS and await further research.
Liu
Tsung-Ta
TT
Graduate Institute of Life Sciences, Shuang Ho Hospital and Taipei Medical University, Taipei, Taiwan, ROC.
Hu
Chou-Hui
CH
Tsai
Chu-Dang
CD
Li
Chuan-Wang
CW
Lin
Yuh-Feng
YF
Wang
Jia-Yi
JY
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D002103:Cadaverine / Q000031:analogs & derivatives / Q000737:chemistry; D018883:Heat Stroke / Q000378:metabolism / Q000503:physiopathology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D009410:Nerve Degeneration / Q000378:metabolism / Q000517:prevention & control*; D010588:Phagosomes / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
C008542:monodansylcadaverine; D002103:Cadaverine