RT Journal Article
SR Electronic
T1 SRF Is Required for Maintenance of Astrocytes in Non-Reactive State in the Mammalian Brain
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0447-19.2020
DO 10.1523/ENEURO.0447-19.2020
VO 8
IS 1
A1 Monika Jain
A1 Soumen Das
A1 Paul P. Y. Lu
A1 Garima Virmani
A1 Sumitha Soman
A1 Surya Chandra Rao Thumu
A1 David H. Gutmann
A1 Narendrakumar Ramanan
YR 2021
UL http://www.eneuro.org/content/8/1/ENEURO.0447-19.2020.abstract
AB Astrocytes play several critical roles in the normal functioning of the mammalian brain, including ion homeostasis, synapse formation, and synaptic plasticity. Following injury and infection or in the setting of neurodegeneration, astrocytes become hypertrophic and reactive, a process termed astrogliosis. Although acute reactive gliosis is beneficial in limiting further tissue damage, chronic gliosis becomes detrimental for neuronal recovery and regeneration. Several extracellular factors have been identified that generate reactive astrocytes; however, very little is known about the cell-autonomous transcriptional mechanisms that regulate the maintenance of astrocytes in the normal non-reactive state. Here, we show that conditional deletion of the stimulus-dependent transcription factor, serum response factor (SRF) in astrocytes (SrfGFAPCKO) results in astrogliosis marked by hypertrophic morphology and increased expression of GFAP, vimentin, and nestin. These reactive astrocytes were not restricted to any specific brain region and were seen in both white and gray matter in the entire brain. This astrogliosis persisted throughout adulthood concomitant with microglial activation. Importantly, the Srf mutant mouse brain did not exhibit any cell death or blood brain barrier (BBB) deficits suggesting that apoptosis and leaky BBB are not the causes for the reactive phenotype. The mutant astrocytes expressed more A2 reactive astrocyte marker genes and the SrfGFAPCKO mice exhibited normal neuronal numbers indicating that SRF-deficient gliosis astrocytes are not neurotoxic. Together, our findings suggest that SRF plays a critical role in astrocytes to maintain them in a non-reactive state.