NMDA受体和vein基因对果蝇交配取向行为的调控研究

Regulation of Mating Orientation Behavior by NMDA Receptor and vein Gene in Drosophila

精神分裂症是一种多基因遗传的复杂性精神疾病,患者通常表现出多类行为异常,并且在性别身份认知上存在不同程度的障碍.我们从果蝇的交配取向行为出发,探究精神分裂症易感同源基因NMDAR(N-甲基-D-天冬氨酸受体基因)和vein(vn)等与求偶行为学的关系.实验结果表明,全神经元范围内抑制NMDA受体亚基dNR1或dNR2的表达均能够显著降低雄性果蝇选择雌性配偶的几率;对相关神经元进行筛选发现,在椭球体(Ellipsoid Body,EB)区而非其他区域神经元抑制NMDA受体亚基表达的果蝇表现出类似的求偶行为障碍.进一步研究发现,神经调节蛋白vn基因突变的果蝇同样出现异常的交配取向行为,而在全神经元同时抑制vn和NMDA受体dNR2亚基蛋白的表达对社交行为的影响,与分别单独抑制没有显著差异.这些结果提示EB区NMDA受体的表达与果蝇的交配取向行为有关,而vn基因可能参与调控这一行为过程.我们的实验结果为以果蝇为模式动物,研究神经递质系统功能障碍对精神分裂症性别认知行为的影响和调控机制提供参考价值.

Schizophrenia is a highly polygenic mental disorder characterized by an imbalance of multiple neurotransmitter systems in pathophysiology.Gender dysphoria(GD)is regarded as a form of cognitive dysfunction which is judged to be the major defect of schizophrenic patients.Based on the unique mating behavior of Drosophila,we studied the relationship between several Drosophila homolog schizophrenia susceptibility genes and courtship behavior.Our results showed that inhibiting the pan-neuronal expression of the NMDA receptor could significantly increase the probability of male-male courtship.However,only the reduced expression of NMDA receptor in the neurons of ellipsoid body(EB)was confirmed to be the cause of this abnormal behavior.Subsequent behavioral screening showed that the Drosophila vein(vn),one schizophrenia susceptibility gene mutants also shown an abnormal mating orientation behavior.And there was no significant difference in the effect of inhibiting the expression of both vn and NMDA receptor dNR2 subunit and separate expression on the courtship behavior.These results suggest that the expression of NMDA receptor in EB region regulated the mating orientation behavior of Drosophila,and vn was involved in this process somehow indirectly.The mechanism underlying this action remains to be further studied.