Taltirelin treatment alleviates PTSD-like symptoms and restores neural oscillations in male mice receiving single prolonged stress.

Thyrotropin-releasing hormone (TRH) plays an important role in the regulation of emotion and cognition. However, whether TRH in the hippocampus participates in the development of post-traumatic stress disorder (PTSD)-like behaviors and the mechanisms involved remain unclear. Transcriptomic analysis was conducted to identify differentially expressed genes (DEGs) in the hippocampus of single prolonged stress (SPS), which is a well-known procedure inducing PTSD-like behaviors in rodents. The expression of pro-TRH and its receptor 1 (TRH-R1) in the hippocampus were assessed using Western blot. Taltirelin (TAL) were employed to examine their regulatory roles in PTSD-like behaviors and neural oscillations. In this study, transcriptomic analysis identified 63 DEGs in the hippocampus of SPS mice compared to controls. The DEGs were mainly involved in hormone activity, and regulated the pathways such as neuroactive ligand-receptor interaction. Western blotting showed that both pro-TRH and its receptor 1 (TRH-R1) were significantly decreased in the hippocampus of the SPS group compared to the control group. TAL treatment remedied PTSD-like behaviors and reversed abnormal hippocampal neural oscillations induced by SPS. Mechanistic investigations revealed that TAL reversed the SPS-induced dysregulation of synaptic proteins in the hippocampus. Together, administration of the TRH analog TAL ameliorates SPS-induced PTSD-like behaviors and restores neural oscillations in mice, probably through mechanisms involving modulation of neuronal synaptic transmission and plasticity.