Characterization of neuroprotective reactive astrocytes in the aging mammalian brain

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PhD; 2023; Centre for neuroscience

The brain manifests cognitive deficits in aging and becomes more vulnerable to neurodegeneration. Astrocytes play several critical roles in the brain, including synapse formation, maturation, elimination, and synaptic plasticity, and impairments in these functions have more tremendous implications for diseases and neuronal dysfunction. Astrocytes sense and respond to different pathological stimuli through a process termed astrocyte reactivity, in which astrocytes undergo molecular, cellular, and functional changes. Generally, reactive astrocytes are considered to be a beneficial partner of neurons in the CNS. However, they can adopt a detrimental state as well, depending on the nature of the stimuli. Recent studies reported that astrocytes take on an LPS-induced neuroinflammatory phenotype during aging, which may facilitate synapse elimination and predispose the brain to neurodegeneration. Our lab recently showed that astrocyte-specific deletion of the stimulus-dependent transcription factor, SRF (SrfGFAPCKO and SrfGFAP−ERCKO) resulted in reactive astrocytes, which supports normal cell counts and brain architecture, normal synapse numbers, synaptic plasticity, and spatial memory and also induced microgliosis.