Chd2 Is Necessary for Neural Circuit Development and Long-Term Memory.
Chd2 Is Necessary for Neural Circuit Development and Long-Term Memory.
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CHD2对于神经回路的发展和长期记忆是必需的。
DOI：
10.1016/j.neuron.2018.09.049
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发表时间：
2018-12-05
期刊：
影响因子：
16.2
通讯作者：
Hunt RF
中科院分区：
文献类型：
--
作者：
Kim YJ;Khoshkhoo S;Frankowski JC;Zhu B;Abbasi S;Lee S;Wu YE;Hunt RF
相当多的证据表明，染色质重塑蛋白（CHD 2）的功能缺失突变导致了广泛的人类神经发育障碍。然而，尚不清楚CHD 2突变如何导致脑功能受损。在这里，我们报告的Chd 2杂合突变的小鼠表现出神经元增殖的缺陷和神经元兴奋性的转变，包括兴奋性和抑制性突触功能的不同变化。进一步的体内实验表明，Chd 2 +/−小鼠表现出异常的皮质节律发生和长期记忆的严重缺陷，与在人类中观察到的表型一致。我们在Chd 2 +/−小鼠中发现了广泛的、年龄依赖性的转录变化，包括神经发生、突触传递和疾病相关基因的改变。由Chd 2 +/−引起的中间神经元密度和记忆缺陷通过Chd 2突变重现，仅限于抑制性神经元的子集，并通过中间神经元移植来纠正。我们的研究结果提供了初步的洞察Chd 2单倍不足如何导致异常的皮层网络功能和受损的记忆。
Considerable evidence suggests loss of function mutations in the chromatin remodeler, CHD2, contribute to a broad spectrum of human neurodevelopmental disorders. However, it is unknown how CHD2 mutations lead to impaired brain function. Here we report mice with heterozygous mutations in Chd2 exhibit deficits in neuron proliferation and a shift in neuronal excitability that included divergent changes in excitatory and inhibitory synaptic function. Further in vivo experiments show Chd2+/− mice displayed aberrant cortical rhythmogenesis and severe deficits in long-term memory, consistent with phenotypes observed in humans. We identified broad, age-dependent transcriptional changes in Chd2+/− mice, including alterations in neurogenesis, synaptic transmission and disease-related genes. Deficits in interneuron density and memory caused by Chd2+/− were reproduced by Chd2 mutation restricted to a subset of inhibitory neurons and corrected by interneuron transplantation. Our results provide initial insight into how Chd2 haploinsufficiency leads to aberrant cortical network function and impaired memory.
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影响因子：
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作者：
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作者：
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通讯作者：
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DOI：
10.1093/brain/awv052
发表时间：
2015-05
期刊：
Brain : a journal of neurology
影响因子：
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作者：
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通讯作者：
Sisodiya SM
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通讯作者：
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