Heat stress induced oxidative damage and perturbation in BDNF/ERK1/2/CREB axis in hippocampus impairs spatial memory

Nishant Ranjan Chauhan, Rahul Kumar, Avinash Gupta, Ramesh Chand Meena, Sarita Nanda, Kamla Prasad Mishra, Shashi Bala Singh

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Heat exposure is an environmental stress that causes diverse heat related pathophysiological changes under extreme conditions. The brain including hippocampal region which is associated with learning and memory is significantly affected by heat stress resulting in memory impairment. However, the effect of heat on the spatial memory remains unclear. The present study aimed to explore the effect of heat stress on hippocampus and spatial memory in rats. Rat model of acute heat stress was used which was divided into two groups, viz. moderate heat stress (MHS) and severe heat stress (SHS). Redox parameters evaluation revealed that MHS and SHS exposure markedly increase the production of malondialdehyde (MDA), oxidised glutathione (GSSG), reactive oxidative species (ROS), protein oxidation level and decrease the reduced glutathione (GSH) levels in the hippocampal tissue. Furthermore, Cresyl Violet (CV) staining of hippocampal region showed higher pyknosis in rats exposed to SHS. Pronounced increase of caspase3 expression and Fluoro Jade-C (FJ-C) positive cells were observed in SHS resulting in neuronal injury and apoptosis in CA3 region of hippocampus culminating in spatial memory deficit. Our data also suggest that heat stress induces phospho Extracellular signal-regulated kinases (pERK)1/2 activation induced by Brain-derived neurotrophic factor (BDNF) leading to further activation of phospho cAMP-response element binding protein (pCREB) under MHS. However, during SHS, BDNF and pCREB expression were completely dysregulated and not sufficient to rescue cognitive decline in rats. In conclusion, SHS induces pathological alterations that include oxidative damage and apoptosis of hippocampal neurons, disturbing BDNF/ERK1/2/CREB axis that may affect spatial memory.

Original languageEnglish (US)
Article number112895
JournalBehavioural Brain Research
Volume396
DOIs
StatePublished - Jan 1 2021
Externally publishedYes

Keywords

  • BDNF/ERK1/2/CREB axis.
  • Heat-stress
  • Hippocampus
  • Memory impairment
  • Oxidative stress
  • Spatial memory

ASJC Scopus subject areas

  • Behavioral Neuroscience

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