Inactivation of BRD7 results in impaired cognitive behavior and reduced synaptic plasticity of the medial prefrontal cortex
Inactivation of BRD7 results in impaired cognitive behavior and reduced synaptic plasticity of the medial prefrontal cortex
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DOI：
10.1016/j.bbr.2015.02.031
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发表时间：
2015-06
影响因子：
2.7
通讯作者：
Yang Xu;Wenyu Cao;Ming Zhou;Changqi Li;Yanwei Luo;Heran Wang;R. Zhao;Shihe Jiang;Jing Yang
中科院分区：
文献类型：
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作者：
Yang Xu;Wenyu Cao;Ming Zhou;Changqi Li;Yanwei Luo;Heran Wang;R. Zhao;Shihe Jiang;Jing Yang
BRD7是一种含溴结构域蛋白（BCP），最近的证据表明BCP在神经发育障碍的发生和发展中的作用。然而，很少有研究调查BRD7在中枢神经系统中的生物学功能。在我们的研究中，发现BRD7广泛表达于小鼠脑的各个区域，包括内侧前额叶皮质（mPFC）、尾壳核（CPu）、海马（Hip）、中脑（Mb）、小脑（Cb），并且主要与神经元共定位，而不与胶质细胞共定位。使用BRD7敲除小鼠模型和一系列行为测试，我们报告说，BRD7的破坏导致认知行为受损，而情感行为不受影响。此外，一系列参与突触可塑性的蛋白质在内侧前额叶皮层减少，并伴随着减少神经元棘密度和树突分支在内侧前额叶皮层。然而，与野生型小鼠相比，在海马体中没有发现显著差异。因此，BRD7可能在调节突触可塑性和影响认知行为中发挥关键作用。
BRD7 is a bromodomain-containing protein (BCP), and recent evidence implicates the role of BCPs in the initiation and development of neurodevelopmental disorders. However, few studies have investigated the biological functions of BRD7 in the central nervous system. In our study, BRD7 was found to be widely expressed in various regions of the mouse brain, including the medial prefrontal cortex (mPFC), caudate putamen (CPu), hippocampus (Hip), midbrain (Mb), cerebellum (Cb), and mainly co-localized with neuron but not with glia. Using a BRD7 knockout mouse model and a battery of behavioral tests, we report that disruption of BRD7 results in impaired cognitive behavior leaving the emotional behavior unaffected. Moreover, a series of proteins involved in synaptic plasticity were decreased in the medial prefrontal cortex and there was a concomitant decrease in neuronal spine density and dendritic branching in the medial prefrontal cortex. However, no significant difference was found in the hippocampus compared to the wild-type mice. Thus, BRD7 might play a critical role in the regulation of synaptic plasticity and affect cognitive behavior.