Abstract

Heat stress (HS) profoundly disrupts thermoregulation, physiological functions, and behavior, leading to adverse health outcomes. The central nervous system is particularly vulnerable to HS, which can impair brain structure and function, trigger neuroinflammation, and induce cognitive deficits. Previous studies have established that the hippocampus plays a critical role in learning, memory, stress responses, and the pathophysiology of mood disorders.

In this study, we investigated the effects of HS by comparing the hippocampal transcriptomes of HS-exposed mice with those of control mice. The results showed that HS did not significantly alter the hippocampus's number, function, distribution, or types of single-nucleotide polymorphisms (SNPs) or insertions/deletions (InDels). However, HS markedly affected gene expression profiles. Transcriptome sequencing identified 210 differentially expressed genes (DEGs) in the hippocampus of HS-exposed mice, including 72 upregulated and 138 downregulated genes.

Gene Ontology (GO) analysis indicated that these DEGs are involved in hippocampal responses to various stimuli—such as chemical agents, oxygen-containing compounds, and peptide hormones—as well as in metabolic processes, including arachidonic acid metabolism, olefinic compound metabolism, and lipid metabolism. For instance, DEGs such as Card14, Ntrk1, Lcn2, Irs4, Cyp2c70, Hamp, Ambp, Gh, and Mup19 exhibited significant differential expression, suggesting these genes may play essential roles in regulating hippocampal function following HS and highlighting potential directions for future research.

Additionally, we examined the protective effects of taurine pretreatment on hippocampal gene expression following HS. The sequencing data showed that taurine alleviated HS-induced changes in 40 DEGs. GO analysis further revealed that taurine modulated 12 DEGs—Ccn1, Egr2, Fos, Arc, Banp, Egr1, Klf2, Egr4, Nfya, Clec14a, Lcn2, and Plin4—which are associated with cognitive function, transcriptional regulation, and vascular development.

Our studies previously showed that Lcn2 participates in HS-induced neuroinflammation. In the HS mouse model, taurine modulated hippocampal inflammation by upregulating neuronal PAS domain protein 4 (Npas4) and downregulating Lcn2, thereby promoting the recovery of cognitive function.

These findings underscore the potential of taurine as a multi-target modulator against HS-induced cognitive impairments and provide a theoretical foundation for developing taurine-based preventive strategies for at-risk populations.