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

• Applicant: Dr. Stefanie Robel
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2011 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 197969167

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.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Harald W. Sontheimer, Ph.D.