Lmtk3-KO Mice Display a Range of Behavioral Abnormalities and Have an Impairment in GluA1 Trafficking
Lmtk3-KO Mice Display a Range of Behavioral Abnormalities and Have an Impairment in GluA1 Trafficking
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DOI：
10.1016/j.neuroscience.2019.06.033
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发表时间：
2019-08-21
期刊：
影响因子：
3.3
通讯作者：
Yamamoto, Tadashi
中科院分区：
文献类型：
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作者：
Montrose, Kristopher;Kobayashi, Shizuka;Yamamoto, Tadashi
越来越多的证据表明，突触能信号和突触可塑性是精神疾病出现的一种方式。本研究通过强调LMTK 3在大脑中的重要性，揭示了这种情况发生的可能机制。对Lmtk 3-KO小鼠的行为分析揭示了许多与精神疾病相关的异常，如过度社交，PPI缺陷和认知功能障碍。氯氮平治疗抑制了Lmtk 3-KO小鼠的这些行为变化。由于突触功能障碍与人类精神疾病有关，我们分析了Lmtk 3-KO小鼠的LTP，发现诱导严重受损。进一步的研究揭示了AMPA刺激后Lmtk 3-KO神经元中GluA 1运输的异常，沿着突触后密度中GluA 1表达的减少。因此，我们假设LMTK 3是参与LTP期间GluA 1运输的重要因素，并且该途径的破坏有助于小鼠出现与人类精神疾病相关的行为。(C)2019年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Accumulating evidence suggests that glutamatergic signaling and synaptic plasticity underlie one of a number of ways psychiatric disorders appear. The present study reveals a possible mechanism by which this occurs, through highlighting the importance of LMTK3, in the brain. Behavioral analysis of Lmtk3-KO mice revealed a number of abnormalities that have been linked to psychiatric disease such as hyper-sociability, PPI deficits and cognitive dysfunction. Treatment with clozapine suppressed these behavioral changes in Lmtk3-KO mice. As synaptic dysfunction is implicated in human psychiatric disease, we analyzed the LTP of Lmtk3-KO mice and found that induction is severely impaired. Further investigation revealed abnormalities in GluA1 trafficking after AMPA stimulation in Lmtk3-KO neurons, along with a reduction in GluA1 expression in the post-synaptic density. Therefore, we hypothesize that LMTK3 is an important factor involved in the trafficking of GluA1 during LTP, and that disruption of this pathway contributes to the appearance of behavior associated with human psychiatric disease in mice. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.