Astrocytes in brain homeostasis and injury

The enormous cerebral capacity of the central nervous system (CNS) relies fundamentally on the interplay of neurons with astrocytes. These glial cells are involved in multiple CNS processes, such as maintaining homeostasis, providing metabolic and trophic support, modulating synaptogenesis, synaptic transmission and plasticity. Astrocytes perform these numerous functions by interacting with millions of synapses while simultaneously associating with other glia cells and the vasculature. During disease and injury, astrocytes protect the CNS from irrevocable damage via a defense program, known as "reactive astrogliosis". Elaborate functional and morphological changes enable astrocytes to contain tissue damage, pathogens, and neuroinflammation, e.g., by creating isolating astrocytic scars. To fulfill all these tasks, astrocytes need to orchestrate complex intracellular processes like multiple membrane trafficking pathways and the dynamic cytoskeleton. We use multi-disciplinary approaches, including live imaging, genetics, CRISPR/Cas9 genome editing, and RNAi, to study in astrocytes the actin cytoskeleton and endolysosomal compartments, like Drebrin-Rab8 dependent tubular endosomes.

Key Publications

Schiweck J, Murk K, Ledderose J, Munster-Wandowski A, Ornaghi M, Vida I, Eickholt BJ. Drebrin controls scar formation and astrocyte reactivity upon traumatic brain injury by regulating membrane trafficking. Nat Commun 2021;12(1):1490. DOI 10.1038/s41467-021-2166

Schiweck J, Eickholt BJ, Murk K. Important Shapeshifter: Mechanisms Allowing Astrocytes to Respond to the Changing Nervous System During Development, Injury and Disease. Front Cell Neurosci 2018;12:261. DOI 10.3389/fncel.2018.00261

People
Kai Murk
Marta Ornaghi
Robert Hülse
Collaborators
Pavla Jendelova (Institute of Experimental Medicine, CAS, Prague)
James Fawcett (Institute of Experimental Medicine, CAS, Prague)