A role for gliotransmission in delayed neuronal death

神经胶质细胞传递在延迟性神经元死亡中的作用

• 批准号: 7394329
• 负责人: Michael M Halassa
• 金额: $ 3.7万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7394329
• 关键词: Agonist; Alzheimer' s Disease; Astrocytes; Attenuated; Brain; Brain Diseases; Calcium; Calcium Signaling; Cells; Cessation of life; Class; Communities; D Glutamate; Disease; Enzymes; Epilepsy; Functional disorder; Ganciclovir; Goals; Hippocampus (Brain); Image; In Situ; Inositol; Intervention; Knowledge; Ligands; Mediating; Mental Depression; Metabolism; Microscopy; Molecular; Molecular Genetics; Molecular Target; Mus; N-Methyl-D-Aspartate Receptors; Neurons; Numbers; Parkinson Disease; Pathology; Physiological Processes; Process; Protein Overexpression; Receptor Activation; Research; Role; Schizophrenia; Seizures; Serine; Signal Transduction; Status Epilepticus; Synaptic plasticity; Techniques; Testing; Trans-Activators; Transgenes; Transgenic Mice; Transgenic Organisms; Venus; attenuation; base; cell type; chemical release; day; design; dihydroxyphenylethylene glycol; falls; in vivo; inositol-1,4,5-trisphosphate 5-phosphatase; insight; neuronal excitability; novel; patch clamp; purinoceptor P2Y1; tripolyphosphate; two-photon; voltage gated channel

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.

描述（由申请人提供）：星形胶质细胞释放许多调节突触可塑性和神经元兴奋性的胶质递质。星形胶质细胞通过释放谷氨酸和D-丝氨酸以钙依赖的方式激活神经元NMDA受体。NMDA受体的过度刺激导致兴奋毒性神经元死亡。初步证据表明，癫痫持续状态（SE）导致星形胶质细胞钙兴奋性的长期增加，这在时间上与SE诱导的神经元死亡相关。我将使用电生理学技术沿着双光子成像来研究胶质传递是否通过刺激NMDA受体导致SE诱导的神经元死亡。这将通过使用星形胶质细胞特异性诱导型转基因来促进，其中肌醇1，4，5三磷酸依赖性钙信号传导已被靶向。星形胶质细胞在脑疾病中的作用知之甚少。本文提出的研究将使更多的了解星形胶质细胞在癫痫中的作用，并可能对许多其他脑部疾病，包括阿尔茨海默病，帕金森病，抑郁症和精神分裂症。这些知识将使科学界能够设计针对这些疾病的新疗法。