Reactive astrogliosis is a common pathological hallmark of central nervous system (CNS) injury, infection, and neurodegeneration, where reactive astrocytes can be protective or detrimental to normal brain functions. Currently, the mechanisms regulating neuroprotective astrocytes and the extent of neuroprotection are poorly understood. Here, we report that conditional deletion of serum response factor (SRF) in adult astrocytes causes reactive-like hypertrophic astrocytes throughout the mouse brain. These SrfGFAP-ERCKO astrocytes do not affect neuron survival, synapse numbers, synaptic plasticity or learning and memory. However, the brains of Srf knockout mice exhibited neuroprotection against kainic-acid induced excitotoxic cell death. Relevant to human neurodegenerative diseases, SrfGFAP-ERCKO astrocytes abrogate nigral dopaminergic neuron death and reduce b-amyloid plaques in mouse models of Parkinson's and Alzheimer's disease, respectively. Taken together, these findings establish SRF as a key molecular switch for the generation of reactive astrocytes with neuroprotective functions that attenuate neuronal injury in the setting of neurodegenerative diseases.
All data generated or analysed during this study are included in the manuscript and supporting file
- Narendrakumar Ramanan
- Narendrakumar Ramanan
- Deepak Nair
- James P Clement
- Swananda Marathe
- Surya Chandra Rao Thumu
- Monika Jain
- Soumen Das
- Arnab Nandi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All the procedures in this study were performed according to the rules and guidelines of the Committee for the Purpose of Control and Supervision of Experimental Animals (CPCSEA), India. The research protocol was approved by the Institutional Animal Ethics Committee (IAEC) of the Indian Institute of Science (Protocol numbers: CAF/Ethics/596/2018 and CAF/Ethics/731/2020).
- Sacha B Nelson, Brandeis University, United States
© 2024, Thumu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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