Srf is required for maintenance of astrocytes in non-reactive state in the mammalian brain

Monika Jain, Soumen Das, Paul P.Y. Lu, Garima Virmani, Sumitha Soman, Surya Chandra Rao Thumu, David H. Gutmann, Narendrakumar Ramanan

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Astrocytes play several critical roles in the normal functioning of the mammalian brain, including ion homeosta-sis, synapse formation, and synaptic plasticity. Following injury and infection or in the setting of neurodegener-ation, 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 (SrfGFAP CKO) 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 apo-ptosis and leaky BBB are not the causes for the reactive phenotype. The mutant astrocytes expressed more A2 reactive astrocyte marker genes and the SrfGFAP CKO 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.

Original languageEnglish
Article numberENEURO.0447-19.2020
Pages (from-to)1-15
Number of pages15
JournaleNeuro
Volume8
Issue number1
DOIs
StatePublished - 2021

Keywords

  • Astrogliosis
  • Gliosis
  • Reactive astrocytes
  • Serum response factor

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