Pathophysiological role of P2X7 receptors in the nervous system

我们在莱比锡和布达佩斯的工作组将致力于阐明神经元和星形胶质细胞P2 X7受体在病理生理状态和疾病，如缺血，神经性疼痛和抑郁症中的参与。据推测，共同的病因因素包括ATP释放增加和P2 X7受体上调，这反过来又通过坏死/凋亡机制触发神经变性。实验将在体外（混合神经元/星形胶质细胞培养物、脑和脊髓切片制备物）和体内条件下进行。各种方法以及转基因和基因敲除动物将被用来证实或驳回我们的假设。鉴于ATP的一般信号传导功能，我们假设变化将发生在外周和中枢神经系统的各个层面，导致神经元、星形胶质细胞和小胶质细胞之间的相互作用受到干扰。新知识的获得可能是开发新治疗策略的基础。

Our workgroups in Leipzig and Budapest will aim at clarifying the involvement of neuronal and astrocytic P2X7 receptors in pathophysiological states and illnesses such as ischemia, neuropathic pain and depression. It is hypothesized that the common etiological factor includes increased ATP release and up-regulation of P2X7 receptors, which in turn trigger via necrotic/apoptotic mechanisms neurodegeneration. Experiments will be performed both under in vitro (mixed neuronal/astrocytic cultures, brain and spinal cord slice preparations), and in vivo conditions. A variety of methods as well as transgenic and knockout animals will be used to confirm or dismiss our hypothesis. In view of the general signalling function of ATP, we assume that changes will occur at all levels of the peripheral and central nervous system leading to a disturbed interaction between neurons, astrocytes and microglia. The acquisition of new knowledge may be a basis for the development of novel therapeutic strategies.