Long Peihua, Ma Qunfei, Wang Zhe, Wang Guanqin, Jiang Jianan, Gao Lu
Department of Physiology, Naval Medical University, Shanghai, 200433, PR China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, 200120, PR China.
Heliyon. 2024 Sep 2;10(17):e37319. doi: 10.1016/j.heliyon.2024.e37319. eCollection 2024 Sep 15.
The organism's normal physiological function is greatly impacted in a febrile environment, leading to the manifestation of pathological conditions including elevated body temperature, dehydration, gastric bleeding, and spermatogenic dysfunction. Numerous lines of evidence indicate that heat stress significantly impacts the brain's structure and function. Previous studies have demonstrated that both animals and humans experience cognitive impairment as a result of exposure to high temperatures. However, there is a lack of research on the effects of prolonged exposure to high-temperature environments on learning and memory function, as well as the underlying molecular regulatory mechanisms. In this study, we examined the impact of long-term heat stress exposure on spatial memory function in rats and conducted transcriptome sequencing analysis of rat hippocampal tissues to identify the crucial molecular targets affected by prolonged heat stress exposure. It was found that the long-term heat stress impaired rats' spatial memory function due to the pathological damages and apoptosis of hippocampal neurons at the CA3 region, which is accompanied with the decrease of growth hormone level in peripheral blood. RNA sequencing analysis revealed the signaling pathways related to positive regulation of external stimulation response and innate immune response were dramatically affected by heat stress. Among the verified differentially expressed genes, the knockdown of in neuronal cell line HT22 significantly enhances the cell apoptosis, suggesting the impaired spatial memory induced by long-term heat stress may at least partially be mediated by the dysregulation of in hippocampal neurons. The uncovered relationship between molecular changes in the hippocampus and behavioral alterations induced by long-term heat stress may offer valuable insights for the development of therapeutic targets and protective drugs to enhance memory function in heat-exposed individuals.
在发热环境中，生物体的正常生理功能会受到极大影响，从而导致包括体温升高、脱水、胃出血和生精功能障碍等病理状况的出现。大量证据表明，热应激会显著影响大脑的结构和功能。先前的研究表明，动物和人类在暴露于高温环境后都会出现认知障碍。然而，对于长期暴露于高温环境对学习和记忆功能的影响以及潜在的分子调控机制，缺乏相关研究。在本研究中，我们检测了长期热应激暴露对大鼠空间记忆功能的影响，并对大鼠海马组织进行了转录组测序分析，以确定受长期热应激暴露影响的关键分子靶点。结果发现，长期热应激会损害大鼠的空间记忆功能，这是由于海马CA3区神经元的病理损伤和凋亡所致，同时外周血中生长激素水平降低。RNA测序分析显示，与外部刺激反应和先天免疫反应的正调控相关的信号通路受到热应激的显著影响。在已验证的差异表达基因中，在神经元细胞系HT22中敲低显著增强了细胞凋亡，这表明长期热应激诱导的空间记忆受损可能至少部分是由海马神经元中的失调介导的。海马分子变化与长期热应激诱导的行为改变之间的揭示关系，可能为开发治疗靶点和保护药物以增强热暴露个体的记忆功能提供有价值的见解。
