GDAP2 Overexpression Affects the Development of Neurons and Dysregulates Neuronal Excitatory Synaptic Transmission
GDAP2 Overexpression Affects the Development of Neurons and Dysregulates Neuronal Excitatory Synaptic Transmission
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Gdap2 过度表达影响神经元发育并失调神经元兴奋性突触传递
DOI：
10.1016/j.neuroscience.2022.02.005
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发表时间：
2022-03-07
期刊：
影响因子：
3.3
通讯作者：
Jing, Wei
中科院分区：
文献类型：
--
作者：
Hu, Danmei;Guo, Yi;Jing, Wei
是一个在人脑中高度表达的基因，编码神经节苷脂诱导分化相关蛋白2(GDAP2)。目前，人们对GDAP2的功能知之甚少。近年来，有报道称GDAP2基因突变可能与遗传性小脑性共济失调有关。在本研究中，我们首先对GDAP2过表达对体外培养的海马神经元的影响进行了初步研究。通过对神经元形态的分析发现，当GDAP2上调时，神经元的复杂性和树突棘的数量增加。电生理记录显示，GDAP2过表达显著增加mEPSCs的频率，提示GDAP2过表达对体外培养的原代培养的海马神经元兴奋性突触传递有调节作用。另一方面，癫痫小鼠模型的行为和场电位记录显示，GDAP2的过度表达与癫痫发作频率的增加有关。综上所述，这项初步研究提示GDAP2的过度表达可能具有一定的致病作用，为癫痫等基因相关疾病的研究提供了新的视角。爱思唯尔有限公司出版。保留所有权利。
is a gene highly expressed in the human brain and encodes ganglioside-induced differentiation-associated protein 2 (GDAP2). At present, little is known about the function of GDAP2. In recent years, it has been reported that mutations in the GDAP2 gene may be involved in hereditary cerebellar ataxia. In this study, we first conducted a preliminary study on the effect of GDAP2 overexpression on cultured primary hippocampal neurons in vitro. By analysing neuronal morphology, it was found that the complexity of neurons and the number of dendritic spines increased when GDAP2 was upregulated. The electrophysiological recordings showed that GDAP2 overexpression significantly increased the frequency of mEPSCs, suggesting that GDAP2 overexpression dysregulates excitatory synaptic transmission in cultured primary hippocampal neurons in vitro. On the other hand, behavioural and field-potential recordings of epileptic mouse models showed that GDAP2 overexpression was associated with increased seizure frequency. In summary, this preliminary study suggested that GDAP2 overexpression may have a certain pathogenic effect, providing a new perspective for the study of gene-related diseases such as epilepsy.(c) 2022 IBRO. Published by Elsevier Ltd. All rights reserved.