Department of Neurology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, China; Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education Taiyuan, China.
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, China.
Neuroscience. 2022 Apr 15;488:32-43. doi: 10.1016/j.neuroscience.2022.02.005. Epub 2022 Feb 12.
GDAP2 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.
GDAP2 是一种在人类大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 基因的突变可能与遗传性小脑共济失调有关。在这项研究中，我们首先对 GDAP2 过表达对体外培养的原代海马神经元的影响进行了初步研究。通过分析神经元形态，发现 GDAP2 上调后神经元的复杂性和树突棘数量增加。电生理记录显示，GDAP2 过表达显著增加了 mEPSC 的频率，提示 GDAP2 过表达在外源培养的原代海马神经元中失调了兴奋性突触传递。另一方面，癫痫小鼠模型的行为和场电位记录显示，GDAP2 过表达与癫痫发作频率增加有关。总之，这项初步研究表明，GDAP2 过表达可能具有一定的致病作用，为癫痫等与基因相关疾病的研究提供了新的视角。
