Effect of stochastic nanoroughness on phenotype and gene expression patterns in astrocytes

Prof. Dr. Prasad Shastri (BIOSS and Institute of Macromolecular Chemistry, University of Freiburg)

All neurodegenerative conditions (Alzheimer’s, multiple sclerosis, Parkinson’s) involve changes to functional status of neurons and astrocytes. In this regard studies have focused primarily on understanding loss-of/gain-of function in neurons. However astrocytes not only provide the structural framework for neuronal organization but have also been shown to form synapses and thus may represent another layer/interface in neuronal communication. Therefore understanding paradigms that impact astrocyte biology is very important. We have recently shown that biophysical cues in the form of tissue associated-nanoroughness can modulate behavior of neurons and their interaction with astrocytes and these interactions involve stretch-activated cation channels. Activation of astrocytes leading to a reactive phenotype (reactive astrocytes, RA) is the basis of astrogliosis and, astrogliosis has been associated with several neurodegeneration conditions. In our ongoing work we have established a biophysical basis for CNS function and continue to unravel a role for tissue nanotopography in defining astrocyte phenotype and cellular and signaling homeostasis in the CNS.