MicroRNA‐219a‐5p−mediated inhibition of CaMKIIγ facilitates vestibular compensation in acute vertigo by promoting protein kinase C expression.

Vestibular compensation (VC) refers to a behavioral recovery process in which firing rates of bilateral vestibular nuclei neurons are rebalanced. Our study aimed to investigate the underlying mechanism by which miR‐219a‐5p regulates Ca2+/calmodulin–dependent protein kinase II γ isoform (CaMKIIγ) and protein kinase C (PKC) in VC. A unilateral vestibular deafferentation rat model was established by unilateral labyrinthectomy (UL), after which VC was evaluated in rats with UL‐induced vertigo‐like behavior by measuring vestibular defect behavior and performing rotarod tests, as well as by BrdU immunohistochemistry on medial vestibular nuclei. We found that miR‐219a‐5p was increased while CaMKIIγ was decreased during VC in the medial vestibular nucleus of rats that had undergone UL. Next, gain‐ and loss‐of‐function assays were conducted to evaluate the effects of miR‐219a‐5p and CaMKIIγ on the vestibular defect behaviors and VC, the results of which suggested that in rats after UL overexpression of CaMKIIγ inhibited VC, while overexpression of miR‐219a‐5p facilitated VC. A dual‐luciferase reporter gene assay identified that miR‐219a‐5p targeted CaMKIIγ. This led to additional experiments showing that miR‐219a‐5p aptomir expression downregulated CaMKIIγ in cortical cells with a concomitant increase in PKC expression, which were verified further in vivo. In summary, in rats with acute vertigo, miR‐219a‐5p overexpression inhibits CaMKIIγ and elevates PKC, thereby facilitating VC. Our study offers possible targets for further evaluation as treatment of acute vertigo in humans. [ABSTRACT FROM AUTHOR]