SRF regulates the generation of neuroprotective reactive astrocytes in the mouse brain

Abstract

In response to injuries, infections or in neurodegenerative disorders, astrocytes get activated to become reactive. This phenomenon is called astrogliosis and is marked by a spectrum of changes which encompasses structural, functional and genetic changes in astrocytes. Until now, the molecular mechanisms regulating astrogliosis remain poorly understood. Traditionally, upregulation of GFAP and cellular hypertrophy were considered to be the markers of astrogliosis. But these markers vary with respect to the degree of astrogliosis and studies are ongoing to fully characterize and understand astrogliosis. On the basis of severity, astrogliosis is broadly divided into three categories mild to moderate, severe diffuse and severe astrogliosis with compact glial scar formation. Mild to moderate astrogliosis is marked by upregulation of GFAP and several other genes. Here, reactive astrocytes become hypertrophic while maintaining their domains. Once the neural insult is resolved, these astrocytes revert back to their non-reactive states. In severe astrogliosis, there is more prominent upregulation of GFAP along with other genes and more hypertrophy of astrocytes as compared to mild to moderate astrogliosis. These reactive astrocytes lose their territories and their processes merge with each other. This may lead to permanent changes in the architecture of the brain. Severe astrogliosis with scar formation includes similar changes as severe astrogliosis including enhanced GFAP expression and hypertrophy of astrocytes, but these changes become much more pronounced. In addition, these reactive astrocytes proliferate and their processes overlap extensively to form a compact, dense and narrow glial scar. Here, the tissue undergoes prominent structural changes, which are long-standing and are likely to persist even after tissue repair is complete...