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小白蛋白神经元中Shank2基因缺失导致小鼠中度多动、自我梳理行为增强及癫痫易感性降低。

Shank2 Deletion in Parvalbumin Neurons Leads to Moderate Hyperactivity, Enhanced Self-Grooming and Suppressed Seizure Susceptibility in Mice.

作者信息

Lee Seungjoon, Lee Eunee, Kim Ryunhee, Kim Jihye, Lee Suho, Park Haram, Yang Esther, Kim Hyun, Kim Eunjoon

机构信息

Department of Biological Sciences, Korea Advanced Institute for Science and Technology (KAIST), Daejeon, South Korea.

Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon, South Korea.

出版信息

Front Mol Neurosci. 2018 Jun 19;11:209. doi: 10.3389/fnmol.2018.00209. eCollection 2018.

Abstract

Shank2 is an abundant postsynaptic scaffolding protein implicated in neurodevelopmental and psychiatric disorders, including autism spectrum disorders (ASD). Deletion of in mice has been shown to induce social deficits, repetitive behaviors, and hyperactivity, but the identity of the cell types that contribute to these phenotypes has remained unclear. Here, we report a conditional mouse line with a deletion restricted to parvalbumin (PV)-positive neurons ( mice). These mice display moderate hyperactivity in both novel and familiar environments and enhanced self-grooming in novel, but not familiar, environments. In contrast, they showed normal levels of social interaction, anxiety-like behavior, and learning and memory. Basal brain rhythms in mice, measured by electroencephalography, were normal, but susceptibility to pentylenetetrazole (PTZ)-induced seizures was decreased. These results suggest that deletion in PV-positive neurons leads to hyperactivity, enhanced self-grooming and suppressed brain excitation.

摘要

Shank2是一种丰富的突触后支架蛋白,与神经发育和精神疾病有关,包括自闭症谱系障碍(ASD)。已证明在小鼠中删除该蛋白会导致社交缺陷、重复行为和多动,但导致这些表型的细胞类型身份仍不清楚。在这里,我们报告了一种条件性小鼠品系,其中该蛋白的缺失仅限于小白蛋白(PV)阳性神经元(小鼠)。这些小鼠在新环境和熟悉环境中均表现出中度多动,在新环境而非熟悉环境中自我梳理行为增强。相比之下,它们的社交互动、焦虑样行为以及学习和记忆水平正常。通过脑电图测量,小鼠的基础脑节律正常,但对戊四氮(PTZ)诱导的癫痫发作的易感性降低。这些结果表明,PV阳性神经元中该蛋白的缺失会导致多动、自我梳理行为增强和脑兴奋性抑制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c97/6018407/319c4ad867a6/fnmol-11-00209-g0001.jpg

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