The effect of astrocyte depletion and repopulation approaches in pathological condition of CNS.

Astrocytes a highly diverse and functionally important class of glial cells in the central nervous system (CNS), are central to maintaining homeostasis, modulating synaptic activity, and supporting neuronal health. These cells exhibit remarkable heterogeneity, with distinct subtypes such as protoplasmic and fibrous astrocytes, each playing specialized roles in CNS physiology. Under pathological conditions, including neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and multiple sclerosis (MS), astrocytes undergo reactive transformations, and adopt either neurotoxic (A1) or neuroprotective (A2) phenotypes. While A1-reactive astrocytes contribute to synaptic dysfunction and exacerbate neuroinflammation, A2-reactive astrocytes promote tissue repair and neuronal survival. Studies using astrocyte depletion models show that their absence disrupts extracellular matrix stability, compromises blood-brain barrier (BBB) integrity, and enhances neuroinflammatory responses, underscoring their dual role in disease progression. Pharmacological strategies such as L-AAA or ganciclovir-mediated depletion highlight the therapeutic potential of modulating astrocyte activity to influence disease outcomes. By unraveling the complexity of astrocyte diversity and its dynamic responses in health and disease, researchers can uncover novel therapeutic targets for a wide range of CNS disorders.