Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 14, 2023

Background: Heat exposure is an environmental stressor that has been associated with cognitive impairment. However, the neural mechanisms underlie this phenomenon have yet to be extensively investigated. Methods: The Morris water maze test was utilized assess performance. RNA sequencing employed discover primary regulators and pathological pathways involved in impairment caused by heat. Prior heat vivo vitro, activation of sarco/endoplasmic reticulum (SR/ER) calcium (Ca2+)-ATPase (SERCA) achieved CDN1163. Hematoxylin-Eosin, Nissl staining, imaging, transmission electron microscopy, western blot immunofluorescence were visualize histological changes, intracellular levels, endoplasmic stress (ERS) markers, apoptosis, synaptic proteins alterations. Results: (HS) significantly induced decline neuronal damage mice. By transcriptome between control (n=5) mice hippocampal tissues, we identified a reduction expression atp2a gene encoding SERCA, accompanied corresponding decrease its protein level. Consequently, dysregulation resulted excessive accumulation ions. Furthermore, HS also activated ERS as evidenced upregulation p-PERK, p-eIF2α, CHOP caspase 3. Consistently, postsynaptic density 95 (PSD95) synaptophysin (SYN) expressions indicated modifications function. Notably, impacts on neurons found mitigated CDN1163 treatment both vitro. Additionally, SERCA-mediated apoptosis attenuated GSK2606414 via inhibiting PERK-eIF2α-CHOP axis not only curtailed level 3, but elevated levels PSD95 SYN. Conclusions: These findings highlight significant impact impairment, further elucidate underlying mechanism involving SERCA/PERK/eIF2α pathway.

Language: Английский