Inhibition of CASK Expression by Virus-mediated RNA Interference in Medial Prefrontal Cortex Affects Social Behavior in the Adult Mouse
Inhibition of CASK Expression by Virus-mediated RNA Interference in Medial Prefrontal Cortex Affects Social Behavior in the Adult Mouse
复制标题
病毒介导的 RNA 干扰内侧前额叶皮层 CASK 表达的抑制影响成年小鼠的社交行为
DOI：
10.11441/shinshumedj.69.45
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Katsuhiko TABUCHI
中科院分区：
文献类型：
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作者：
Xueshan CAO;Wen QIU;Bo PANG;Mengyun ZHOU;Anuradha MEHTA;Qi GUO;Yoshinori SHIRAI;Takuma MORI;Katsuhiko TABUCHI
背景：钙/钙调蛋白依赖性丝氨酸蛋白激酶（CASK）是一种突触支架蛋白，CASK 基因的突变已在各种类型的神经发育障碍中被发现。社交行为缺陷是许多神经发育障碍的常见症状，也伴随 CASK 相关疾病。内侧前额叶皮层 (mPFC) 深层被认为负责社交行为。 方法：为了研究 CASK 缺陷对社交行为的影响，我们通过使用腺相关病毒 (AAV) 注射引入 CASK 短发夹 RNA 来产生 mPFC 特异性 CASK 敲除小鼠。我们使用旷场和三室装置研究了CASK敲低和表达增强型绿色荧光蛋白（EGFP）的AAV注射对照小鼠的行为。结果：CASK敲低小鼠在旷场观察中表现出正常的运动活动、焦虑水平和重复行为，但它们在与幼年小鼠的相互社交互动方面表现出缺陷。在三室测试中，与对照小鼠相似的水平上，CASK 敲低小鼠与新型幼年小鼠的互动程度高于空笼小鼠，这表明社会认知是完整的。另一方面，新靶标小鼠和预先暴露的小鼠之间的相互作用没有观察到显着差异，这表明CASK敲低小鼠的社交记忆能力受损。结论：通过使用mPFC特异性CASK敲低小鼠，我们发现该区域的CASK缺陷会影响社交记忆能力。我们的研究结果不仅提供了对 CASK 相关疾病的见解，还提供了与社交缺陷相关的各种神经发育障碍的见解。
Background: Calcium/calmodulin-dependent serine protein kinase (CASK) is a synaptic scaffolding protein and mutations in the CASK gene have been identified in various types of neurodevelopmental disorders. Deficit in social behavior is a common symptom of many neurodevelopmental disorders and also accompanies CASK related disorders. The deep layer of the medial prefrontal cortex (mPFC) has been suggested to be responsible for social behavior.Methods: To study the effect of CASK deficiency on social behavior, we generated mPFC specific CASK knockdown mice by introducing CASK short-hairpin RNA using adeno-associated viral (AAV) injection. We studied the behaviors of CASK knockdown and enhanced green fluorescent protein (EGFP) expressing AAV injected control mice using open field and three-chamber apparatus.Results: CASK knockdown mice showed normal locomotor activity, anxiety level, and repetitive behavior in the observation in the open field arena, but they showed deficit in reciprocal social interaction with a juvenile mouse. In the three-chamber test, CASK knockdown mice showed more interaction with a novel juvenile mouse than an empty cage at a similar level to control mice, suggesting that social recognition is intact. On the other hand, no significant difference was observed in the interaction between a novel target mouse and a pre-exposed mouse, suggesting that social memory ability was impaired in the CASK knockdown mice.Conclusion: By using mPFC specific CASK knockdown mice, we found that CASK deficiency in this area affects the social memory ability. Our results provide insights not only into CASK related disorders, but also a wide range of neurodevelopmental disorders associated with social deficits.