Betahistine Normalizes the State of Mitochondria in Deiters Neurons during Vestibular Stimulation

Abstract

In this work, the state of mitochondria in neurons of the lateral vestibular nucleus of Deiters in mice after 8-hour vestibular stimulation was studied. It was shown that significant changes occurred in the mitochondria of Deiters neurons one hour after stimulation: an increase in area, disruption of the cristae structure, and the presence of mitophagosomes. At the same time, the level of mRNA of proteins-markers of mitochondrial biogenesis (PGC-1α), their division (DRP-1), and the fusion of the outer and inner mitochondrial membranes (MFN1, MFN2, OPA) increased, indicating the activation of mitogenesis in Deiters neurons as a result of stimulation of the vestibular system. The introduction per os of betahistine 30 min before stimulation at a dose of 300 mg/kg prevented mitochondrial disruptions and the formation of mitophagosomes. The obtained data indicate that under increased vestibular stimulation, Deiters neurons can undergo significant damage. The revealed mechanisms of mitochondrial damage allow us to define a potential strategy for the treatment of diseases associated with impaired mitochondrial dynamics (e.g., neurodegenerative diseases or ischemia).