Department of Neuroscience and Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Mol Neurobiol. 2011 Jun;43(3):147-54. doi: 10.1007/s12035-011-8163-7. Epub 2011 Jan 14.
Reactive astrocytes are associated with a vast array of central nervous system (CNS) pathologies. The activation of astrocytes is characterized by changes in their molecular and morphological features, and depending on the type of damage can also be accompanied by inflammatory responses, neuronal damage, and in severe cases, scar formation. Although reactive astrogliosis is the normal physiological response essential for containing damage, it can also have detrimental effects on neuronal survival and axon regeneration, particularly in neurodegenerative diseases. It is believed that progressive changes in astrocytes as they become reactive are finely regulated by complex intercellular and intracellular signaling mechanisms. However, these have yet to be sorted out. Much has been learned from gain-of-function approaches in vivo and culture paradigms, but in most cases, loss-of-function genetic studies, which are a critical complementary approach, have been lacking. Understanding which signaling pathways are required to control different aspects of astrogliosis will be necessary for designing therapeutic strategies to improve their beneficial effects and limit their detrimental ones in CNS pathologies. In this article, we review recent advances in the mechanisms underlying the regulation of aspects of astrogliosis, with the main focus on the signaling pathways that have been studied using loss-of-function genetic mouse models.
反应性星形胶质细胞与中枢神经系统（CNS）的多种病理变化有关。星形胶质细胞的激活表现为其分子和形态特征的改变，并且根据损伤的类型，还可能伴有炎症反应、神经元损伤，在严重的情况下，还会形成瘢痕。虽然反应性星形胶质细胞增生是包含损伤所必需的正常生理反应，但它也会对神经元存活和轴突再生产生有害影响，特别是在神经退行性疾病中。据信，星形胶质细胞在变得反应性时的渐进性变化是由复杂的细胞间和细胞内信号机制精细调节的。然而，这些机制尚未被阐明。在体内和培养模型的功能获得性方法中已经学到了很多，但在大多数情况下，缺乏关键的互补方法——功能丧失性遗传研究。了解控制星形胶质细胞不同方面的信号通路对于设计治疗策略以改善其在 CNS 病理中的有益作用并限制其有害作用是必要的。在本文中，我们回顾了调节星形胶质细胞各个方面的机制的最新进展，主要关注使用功能丧失性遗传小鼠模型研究的信号通路。
