A role for gliotransmission in delayed neuronal death

描述(申请人提供)：星形胶质细胞释放一些神经递质，调节突触的可塑性和神经元的兴奋性。星形胶质细胞通过钙依赖的方式释放谷氨酸和D-丝氨酸来激活神经元NMDA受体。NMDA受体的过度刺激会导致兴奋性毒性神经元死亡。初步证据表明，癫痫持续状态(SE)导致星形胶质细胞钙离子兴奋性的持续增加，这与SE诱导的神经元死亡有时间上的相关性。我将使用电生理技术和双光子成像来询问神经胶质传递是否通过刺激NMDA受体而导致SE诱导神经元死亡。这将通过使用星形胶质细胞特异的可诱导转基因来促进这一点，其中肌醇1，4，5三磷酸依赖的钙信号已成为靶点。星形胶质细胞在脑部疾病中的作用还知之甚少。本文提出的研究将对星形胶质细胞在癫痫中的作用提供更多的见解，并可能对许多其他大脑疾病，包括阿尔茨海默病、帕金森氏病、抑郁症和精神分裂症提供更多的见解。这一知识将使科学界能够设计针对这些疾病的新疗法。

DESCRIPTION (provided by applicant): Astrocytes release a number of gliotransmitters which modulate synaptic plasticity and neuronal excitability. Astrocytes activate neuronal NMDA receptors by releasing glutamate and D-serine in a calcium dependent fashion. Hyper-stimulation of the NMDA receptor results in excitotoxic neuronal death. Preliminary evidence indicates that status epilepticus (SE) results in a prolonged increase in astrocytic calcium excitability that is temporally correlated with SE-induced neuronal death. I will use electrophysiological techniques along with two-photon imaging to ask whether gliotransmission causes SE-induces neuronal death by stimulating the NMDA receptor. This will be facilitated by the use of astrocyte-specific inducible transgenic where inositol 1,4,5 triphosphate-dependent calcium signaling has been targeted. The role of astrocytes in brain disorders is poorly understood. The research propsed herein will give more insight to the role of astrocytes in epilepsy, and potentially, to many other brain disorders including Alzheimer's disease, Parkinson's disease, depression and schizophrenia. This knowledge will allow the scientific community to design novel treatments to target these disorders.