Different types of reactive astrocytes and their physiology - How do they influence brain pathology?

不同类型的反应性星形胶质细胞及其生理学 - 它们如何影响大脑病理学？

• 批准号: 197969167
• 负责人: Dr. Stefanie Robel
• 金额: --
• 依托单位: School of Medicine
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/197969167?language=en
• 关键词: Different; types; reactive; astrocytes; their

Astrocytes react to all types of CNS injury with a process called reactive astrogliosis. During this process astrocytes gradually change their morphology and biochemical profile dependent on the type and severity of the injury. Previous findings indicate that loss of astrocyte endfeet polarity, e.g. redistribution or loss of the potassium channel Kir4.1, the glutamate transporter Glt-1 and the water channel Aqp4 is a hallmark of reactive gliosis, which may be associated with their proliferative response. In contrast to models of acute injury, the gliosis observed in the conditional b1-integrin KO animals does not present with proliferation providing an experimental model to examine the impact of gliosis on astrocyte physiology separated from the effects of dedifferentiation. To which extent fully dedifferentiated astrocytes after acute trauma differ in their biophysical properties from non-proliferative reactive astrocytes in the chronic gliosis in b1-integrin deficient mice will be investigated. Recent findings suggest that modified astroglial function may have a role in the generation and spread of seizures and epilepsy is often accompanied by massive reactive gliosis. The impact and causality of the alterations of astrocytes during the course of disease, however, is poorly understood. Currently available animal models of acquired epilepsy are associated with cell death and/or major structural changes of the brain that complicate the investigation of causalities in neuron-glia interaction. The deletion of b1-integrin in astrocytes causes a widespread reactive gliosis with most hallmarks known for reactive astrocytes, but is devoid of massive cell death or abnormal cortical organization and associated secondary effects. In the proposed project the physiological consequences of chronic astrogliosis will be investigated particularly in regard to its potentially causative role in the development of epilepsy.

星形胶质细胞对所有类型的CNS损伤都有反应，其过程称为反应性星形胶质细胞增生。在此过程中，星形胶质细胞根据损伤的类型和严重程度逐渐改变其形态和生化特征。以前的研究结果表明，星形胶质细胞端足极性的丧失，例如钾通道Kir4.1、谷氨酸转运蛋白Glt-1和水通道Aqp 4的重新分布或丧失，是反应性神经胶质增生的标志，这可能与它们的增殖反应有关。与急性损伤模型相反，在条件性β 1-整联蛋白KO动物中观察到的神经胶质增生不存在增殖，提供了一种实验模型来检查神经胶质增生对星形胶质细胞生理学的影响，与去分化的影响分开。将研究急性创伤后完全去分化的星形胶质细胞在生物物理性质上与b1-整联蛋白缺陷小鼠慢性胶质增生中非增殖反应性星形胶质细胞的差异程度。最近的研究结果表明，修改星形胶质细胞的功能可能在癫痫发作和癫痫的产生和蔓延的作用往往伴随着大规模的反应性胶质细胞增生。然而，对疾病过程中星形胶质细胞改变的影响和因果关系知之甚少。目前获得性癫痫的动物模型与细胞死亡和/或大脑的主要结构变化有关，这使得神经元-胶质细胞相互作用中因果关系的研究复杂化。星形胶质细胞中整合素β 1的缺失导致广泛的反应性胶质增生，具有已知的反应性星形胶质细胞的大多数标志，但没有大量细胞死亡或异常皮质组织和相关的继发性效应。在拟议的项目中，慢性星形胶质细胞增生的生理后果将特别是在其潜在的致病作用，在癫痫的发展进行调查。