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.

中文翻译：

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MicroRNA-219a-5p介导的CaMKIIγ抑制通过促进蛋白激酶C表达促进急性眩晕的前庭代偿

前庭代偿 (VC) 是指一种行为恢复过程，其中双侧前庭核神经元的放电率重新平衡。我们的研究旨在研究 miR-219a-5p 调节 VC 中 Ca2+/钙调蛋白依赖性蛋白激酶 II γ 同种型 (CaMKIIγ) 和蛋白激酶 C (PKC) 的潜在机制。通过单侧迷路切除术（UL）建立单侧前庭去传入神经大鼠模型，然后通过测量前庭缺损行为和执行旋转棒试验以及对内侧前庭核进行 BrdU 免疫组织化学评估 VC 在具有 UL 诱导的眩晕样行为的大鼠中. 我们发现，在接受 UL 的大鼠的内侧前庭核中，在 VC 期间，miR-219a-5p 增加，而 CaMKIIγ 减少。下一个，进行了功能获得和功能丧失试验以评估 miR-219a-5p 和 CaMKIIγ 对前庭缺损行为和 VC 的影响，结果表明在大鼠 UL 过表达 CaMKIIγ 后抑制了 VC，而过表达miR-219a-5p 促进 VC。双荧光素酶报告基因检测确定 miR-219a-5p 靶向 CaMKIIγ。这导致了额外的实验，表明 miR-219a-5p aptomir 表达下调皮质细胞中的 CaMKIIγ，伴随着 PKC 表达的增加，这在体内得到了进一步验证。总之，在急性眩晕大鼠中，miR-219a-5p 过表达抑制 CaMKIIγ 并升高 PKC，从而促进 VC。我们的研究为进一步评估人类急性眩晕的治疗提供了可能的目标。