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.

热暴露是一种环境压力，在极端条件下会导致多种与热相关的病理生理变化。包括与学习和记忆相关的海马区在内的大脑受到热应激的显着影响，导致记忆障碍。然而，热量对空间记忆的影响仍不清楚。本研究旨在探讨热应激对大鼠海马和空间记忆的影响。采用急性热应激大鼠模型，分为两组，即。中度热应激（MHS）和重度热应激（SHS）。氧化还原参数评估显示，MHS 和 SHS 暴露显着增加了丙二醛 (MDA)、氧化型谷胱甘肽 (GSSG)、活性氧化物质 (ROS)、蛋白质氧化水平并降低海马组织中还原型谷胱甘肽 (GSH) 水平。此外，海马区的甲酚紫 (CV) 染色显示暴露于 SHS 的大鼠更高的固缩。在 SHS 中观察到 caspase3 表达和氟玉-C (FJ-C) 阳性细胞的显着增加，导致海马 CA3 区域的神经元损伤和细胞凋亡，最终导致空间记忆缺陷。我们的数据还表明，热应激会诱导由脑源性神经营养因子 (BDNF) 诱导的磷酸化细胞外信号调节激酶 (pERK)1/2 激活，从而导致 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 ​​表达完全失调，不足以挽救大鼠的认知能力下降。综上所述，