Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organisation (DRDO), Lucknow Road, Timarpur, Delhi 110054, India.
Department of Biochemistry, Daulat Ram College, University of Delhi North Campus, Delhi 110007, India.
Behav Brain Res. 2021 Jan 1;396:112895. doi: 10.1016/j.bbr.2020.112895. Epub 2020 Sep 3.
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.
热暴露是一种环境应激，在极端条件下会引起多种与热相关的病理生理变化。大脑包括与学习和记忆相关的海马区，会受到热应激的显著影响，导致记忆障碍。然而，热对空间记忆的影响尚不清楚。本研究旨在探讨热应激对大鼠海马区和空间记忆的影响。采用急性热应激大鼠模型，分为中度热应激（MHS）和重度热应激（SHS）两组。氧化还原参数评估显示，MHS 和 SHS 暴露显著增加海马组织中丙二醛（MDA）、氧化型谷胱甘肽（GSSG）、活性氧（ROS）、蛋白质氧化水平的产生，降低还原型谷胱甘肽（GSH）水平。此外，海马区 Cresyl Violet（CV）染色显示，暴露于 SHS 的大鼠出现更高的固缩。SHS 导致 caspase3 表达明显增加和 Fluoro Jade-C（FJ-C）阳性细胞增多，导致海马 CA3 区神经元损伤和凋亡，最终导致空间记忆缺陷。我们的数据还表明，热应激通过脑源性神经营养因子（BDNF）诱导磷酸化细胞外信号调节激酶（pERK）1/2 的激活，导致 MHS 下磷酸化 cAMP 反应元件结合蛋白（pCREB）的进一步激活。然而，在 SHS 期间，BDNF 和 pCREB 的表达完全失调，不足以挽救大鼠的认知能力下降。总之，SHS 引起的病理改变包括海马神经元的氧化损伤和凋亡，干扰 BDNF/ERK1/2/CREB 轴，可能影响空间记忆。
