TRPV4 activation by core body temperature has multimodal functions in the central nervous system.

Brain temperature is strictly regulated by various endogenous mechanisms and significantly contributes to brain function in homeothermic animals, making it an important factor for health. Thermosensitive transient receptor potential (TRP) channels convert temperature information into electrical signals through cation influx. In particular, TRPV4 is involved in the regulation of brain function. TRPV4, constitutively active in neurons through its activation by brain temperature, increases neuronal firing. TRPV4KO mice have electroencephalogram abnormalities, resulting in depression-like and social behavioral abnormalities. This basic function of TRPV4, as a translator of brain temperature information, has been implicated in several diseases, including epilepsy and stress-induced depression. In addition to its neuronal functions, TRPV4 has many key functions in glia and vasculature that depend on brain temperature and contribute to brain activity. In this review, I summarize the importance of TRPV4 activities in relation to brain temperature and focus on how hyperthermia-induced TRPV4 dysfunction exacerbates brain diseases.