Shaping the glial scar during CNS injury by manipulating the actin cytoskeleton in astrocytes

• Applicant: Professorin Dr. Britta Eickholt
• Subject Area: Experimental Models for the Understanding of Nervous System Diseases ; Molecular Biology and Physiology of Neurons and Glial Cells ; Cell Biology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 495290401

Our work identified that the actin-binding protein Drebrin (DBN) is a key component in astrocyte reactivity in response to CNS damage. Following CNS injury, the upregulation of DBN in astrocytes controls their participation in glial scar formation. In the absence of DBN, astrocytes fail to undergo the polarity and cytoskeletal changes essential for the formation of astrocyte limitans barriers at the site ofinjury. This proposal will examine the consequences of incomplete astrocytic responses due to DBN-loss in vivo and in vitro. In cooperation with Prof. Dr. Pavla Jendelova, Czech Academy of Sciences (CAS), Prague, we will perform a SCI model in DBN deficient mice, and analyze scar formation, inflammation, BBB sealing and axon regeneration. In addition to this we will exploit biochemistry and mass spectrometry to analyze the upstream regulatory principles of DBN in the context of an in vitro scratch injury model. In combination, our studies will provide a novelunderstanding of the cellular and signaling components regulating the glial scar, which are involved in regenerative failure in SCI.

• DFG Programme: Research Grants
• International Connection: Czech Republic
• Cooperation Partner: Professorin Pavla Jendelová, Ph.D.