丙戊酸诱导的焦虑和抑郁行为在 p39 Cdk5 激活剂缺陷型小鼠中得到改善。
Valproic Acid-Induced Anxiety and Depression Behaviors are Ameliorated in p39 Cdk5 Activator-Deficient Mice.
机构信息
Laboratory of Molecular Neuroscience, Department of Biological Sciences, Tokyo Metropolitan University, Minami-osawa, Hachioji, Tokyo, 192-0397, Japan.
Department of Life Science and Medical Bio-Science, Waseda University, Shinjuku, Tokyo, 162-0056, Japan.
出版信息
Neurochem Res. 2022 Sep;47(9):2773-2779. doi: 10.1007/s11064-022-03642-9. Epub 2022 Jun 8.
Valproic acid (VPA) is a drug used for the treatment of epilepsy, seizures, migraines, and bipolar disorders. Cyclin-dependent kinase 5 (Cdk5) is a Ser/Thr kinase activated by p35 or p39 in neurons and plays a role in a variety of neuronal functions, including psychiatric behaviors. We previously reported that VPA suppressed Cdk5 activity by reducing the expression of p35 in cultured cortical neurons, leaving p39 unchanged. In this study, we asked for the role of Cdk5 in VPA-induced anxiety and depression behaviors. Wild-type (WT) mice displayed increased anxiety and depression after chronic administration of VPA for 14 days, when the expression of p35 was decreased. To clarify their relationship, we used p39 knockout (KO) mice, in which p35 is the only Cdk5 activator. When p39 KO mice were treated chronically with VPA, unexpectedly, they exhibited fewer anxiety and depression behaviors than WT mice. The effects were p39 cdk5r2 gene-dosage dependent. Together, these results indicate that Cdk5-p39 plays a specific role in VPA-induced anxiety and depression behaviors.
丙戊酸（VPA）是一种用于治疗癫痫、癫痫发作、偏头痛和双相情感障碍的药物。周期蛋白依赖性激酶 5（Cdk5）是一种 Ser/Thr 激酶，在神经元中被 p35 或 p39 激活，在多种神经元功能中发挥作用，包括精神行为。我们之前报道过，VPA 通过降低培养的皮质神经元中 p35 的表达来抑制 Cdk5 活性，而 p39 不变。在这项研究中，我们探讨了 Cdk5 在 VPA 诱导的焦虑和抑郁行为中的作用。慢性给予 VPA 14 天后，野生型（WT）小鼠显示出焦虑和抑郁增加，此时 p35 的表达减少。为了阐明它们之间的关系，我们使用了 p39 敲除（KO）小鼠，其中 p35 是唯一的 Cdk5 激活剂。当 p39 KO 小鼠慢性给予 VPA 时，出乎意料的是，它们表现出的焦虑和抑郁行为比 WT 小鼠少。这些作用与 p39-cdk5r2 基因剂量有关。总之，这些结果表明 Cdk5-p39 在 VPA 诱导的焦虑和抑郁行为中发挥特定作用。
Zotero 插件