Heat stroke induces autophagy as a protection mechanism against neurodegeneration in the brain

Tsung Ta Liu, Chou Hui Hu, Chu Dang Tsai, Chuan Wang Li, Yuh Feng Lin, Jia Yi Wang

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)643-648
Number of pages6
JournalShock
Volume34
Issue number6
DOIs
Publication statusPublished - Dec 2010

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Keywords

  • autophagy
  • Fluoro-Jade B
  • Heat stroke
  • monodansylcadaverine
  • neurodegeration

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

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