Investigation of Vasopressin receptors function in neural cell survival system and development of neural-protection therapy

在这项研究中，加压素（AVP）的神经细胞死亡的作用进行了检查。基因表达分析和免疫组化分析显示，海马神经元和星形胶质细胞表达V1 a受体和V1 b受体，海马星形胶质细胞表达AVP。AVP可减轻红藻氨酸诱导的海马神经元死亡。海人酸诱导的海马变性模型显示，V1 a受体和V1 b受体敲除小鼠的癫痫发作严重程度分别比野生型小鼠降低。提示AVP可通过V1 a和/或V1 b受体保护海马神经元，AVP既可直接保护神经元，也可通过星形胶质细胞间接保护海马神经元。另一方面，对红藻氨酸诱导的海马变性模型中的神经变性的免疫组织化学分析显示，V1 a受体敲除小鼠中红藻氨酸诱导的神经变性比V1 b受体敲除小鼠中的更严重。提示V1 a受体和V1 b受体在神经保护功能上存在差异。因此，这表明，研究AVP对胶质细胞功能以及神经功能的作用，可以为使用AVP和/或AVP激动剂/拮抗剂治疗神经变性疾病提供新的治疗策略。

In this study, the roles of vasopressin(AVP) for neural cell death were examined. The gene expression analysis and innmunohistochemical analysis revealed that V1a receptor and V1b receptor were expressed in hippocampal neuron and astrocyte, and that AVP was expressed in hippocampal astrocyte. AVP could reduce the kainic-acid induced hippocampal neural death in vitro. Kainic-acid induced hippocampus degeneration model showed that seizure severity of V1a receptor and V1b receptor knock out mice were reduced compare to wild type mice, respectively. These results suggest that AVP could protect hippocampal neuron via V1a and/or V1b receptor, and that AVP could protect hippocampal neuron via astrocyte indirectly as well as to neuron directly. On the other hand, immunohistochemical analysis for neural degeneration in kainic-acid induced hippocampus degeneration model showed that kainic-induced neural degeneration was more severe in V1a receptor knock out mice than in V1b receptor knock out mice. This result suggests that there are difference of neural protective function between V1a receptor and V1b receptor. Thus, it is suggest that investigation of AVP function for glial function as well as neural function lead to novel therapy strategy for neural degeneration disease using AVP and/or AVP agonist/antagonist.