The protective effect of heat acclimation from hypoxic damage in the brain involves changes in the expression of glutamate receptors

Assaf Yacobi, Yael Stern Bach, Michal Horowitz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Long-term heat acclimation (34 °C, 30d) alters the physiological responses and the metabolic state of organisms. It also improves ability to cope with hypoxic stress via a cross-tolerance mechanism. Within the brain, the hippocampal and frontal cortex neurons are the most sensitive to hypoxia and cell death is mainly caused by calcium influx via glutamate-gated ion channels, specifically NMDA and AMPA receptors. GluN1 subunit levels of NMDA-R correspond to NMDA-R levels. GluN2B/GluN2A subunit ratio is a qualitative index of channel activity; a higher ratio implies lower calcium permeability. The GluA2 subunit of AMPA-R controls channel permeability by inhibiting calcium penetration. Here, in rats model we (i)used behavioral-assessment tests to evaluate heat acclimation mediated hypoxic (15’ 4.5 ± 0.5% O2) neuroprotection, (ii) measured protein and transcript levels of NMDA-R and AMPA-R subunits before and after hypoxia in the hippocampus and the frontal cortex, to evaluate the role of Ca2+ in neuro-protection/cross-tolerance. Behavioral tests confirmed hypoxic tolerance in long-term (30d) but not in short-term (2d) heat acclimated rats. Hypoxic tolerance in the long-term acclimated phenotype was accompanied by a significant decrease in basal NMDA receptor GluN1 protein and an increase in its mRNA. The long-term acclimated rats also showed post ischemic increases in the GluN2B/GluN2A subunit ratio and GluA2 subunit of the AMPA receptor, supporting the hypothesis that reduced calcium permeability contributes to heat acclimation mediated hypoxia cross-tolerance. Abrupt post ischemic change in GluN2B/GluN2A subunit ratio with no change in NMDA-R subunits transcript levels implies that post-translational processes are inseparable acclimatory cross-tolerance mechanism.

Original languageAmerican English
Pages (from-to)57-65
Number of pages9
Issue number1
StatePublished - 30 Jun 2014

Bibliographical note

Funding Information:
This study was supported by the Research Committee of the Faculty of Dentistry of The Hebrew University.

Publisher Copyright:
© 2014, Copyright © 2014 Landes Bioscience.


  • AMPA receptors
  • NMDA receptors
  • brain hypoxia
  • heat acclimation mediated cross-tolerance


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