Betahistine attenuates vestibular stimulation-induced mitochondrial damage and neuroinflammation in Deiters' neurons

Dysfunction of the vestibular nuclei, which can arise from various causes, is a common problem, affecting more than a third of people over 40. Its characteristic symptom is vestibular vertigo. This dysfunction is also associated with neurodegenerative diseases. To model vestibular disorders, mice were subjected to rotation for eight hours. They were then given two doses of betahistine (200 mg/kg), one and 24 h after stimulation. Results showed that this treatment affected the animals' open-field behavior, as well as the structure of Deiters' nucleus. One hour after stimulation, significant mitochondrial changes were detected in Deiters' neurons, including an increase in mitochondrial area, disruption of cristae structure, and the presence of mitophagosomes. Betahistine treatment mitigated these effects, reducing both mitochondrial damage and mitophagosome formation, and induced the formation of a special donut-shaped mitochondria, promoting the preservation of membrane potential. Furthermore, betahistine attenuated neuroinflammation, as evidenced by the state of microglia and astrocytes. These results clarify the mechanism of vestibular-induced damage to the Deiters nucleus and identify betahistine as a potential therapeutic agent for neurodegenerative diseases and ischemia.