Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China.
Department of Laboratory Medicine, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, China.
Int Immunopharmacol. 2024 Dec 25;143(Pt 1):113376. doi: 10.1016/j.intimp.2024.113376. Epub 2024 Oct 14.
Heat stress (HS) induces various pathophysiological responses in the brain, encompassing neuroinflammation and cognitive impairments. Although taurine has been reported to possess anti-inflammatory and cognitive-enhancing properties, its role and mechanisms in HS-induced cognitive impairment remain unclear. This study supplemented mice exposed to HS with taurine to assess its effect on cognitive function in a HS-induced mouse model. The results revealed that taurine ameliorated cognitive deficits following HS in mice and mitigated HS-induced astrocyte and microglia activation as well as blood-brain barrier (BBB) damage in the hippocampus. Mechanistically, Mechanistically, transcriptome sequencing was employed to identify that taurine regulates neuronal PAS domain protein (Npas4) and lipocalin 2 (Lcn2) during HS. Taurine was found to modulate hippocampal inflammation and influence cognitive function by upregulating Npas4 and downregulating Lcn2 after HS. Subsequently, molecular docking and AnimalTFDB database calculations were conducted, revealing that taurine might regulate the expression of Npas4 and Lcn2 by modulating the regulatory transcription factors (TFs) RE1 silencing transcription factor (REST) and nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1). Our findings demonstrate that taurine enhances the recovery of cognitive function through Npas4 and Lcn2 following HS, providing a theoretical basis for the clinical application of taurine in preventing or treating HS-induced cognitive impairment.
热应激（HS）会引起大脑的各种病理生理反应，包括神经炎症和认知障碍。虽然牛磺酸已被报道具有抗炎和增强认知的特性，但它在 HS 引起的认知障碍中的作用和机制尚不清楚。本研究通过给暴露于 HS 的小鼠补充牛磺酸，来评估其对 HS 诱导的小鼠模型中认知功能的影响。结果表明，牛磺酸改善了 HS 后小鼠的认知缺陷，并减轻了 HS 诱导的海马星形胶质细胞和小胶质细胞激活以及血脑屏障（BBB）损伤。从机制上讲，转录组测序被用来确定牛磺酸在 HS 期间调节神经元 PAS 结构域蛋白（Npas4）和脂联素 2（Lcn2）。牛磺酸被发现通过 HS 后上调 Npas4 和下调 Lcn2 来调节海马炎症和影响认知功能。随后，进行了分子对接和动物 TFDB 数据库计算，表明牛磺酸可能通过调节调节转录因子（TFs）RE1 沉默转录因子（REST）和 B 细胞核因子 kappa 轻肽基因增强子 1（NFKB1）来调节 Npas4 和 Lcn2 的表达。我们的研究结果表明，牛磺酸通过 HS 后的 Npas4 和 Lcn2 增强认知功能的恢复，为牛磺酸在预防或治疗 HS 引起的认知障碍的临床应用提供了理论依据。
