Astrocytes Lingering at a Crossroads: Neuroprotection and Neurodegeneration in Neurocognitive Dysfunction
Xiaoxia Xu, Bin Mei, Yue Yang, Jinjun Li, Juntao Weng, Yueyue Yang, Qianyun Zhu, Honghai Zhang, Xuesheng Liu
Abstract
Astrocytes, a major class of glial cells in the central nervous system, play a fundamental role in maintaining homeostasis, supporting neuronal function, and regulating synaptic activity. Recent studies have increasingly highlighted the pivotal role of astrocytes in the initiation and progression of neurocognitive dysfunction. Alterations in astrocytic morphology and functionality have been strongly associated with the onset of cognitive impairments, positioning astrocytes as key regulators in neurocognitive processes. Astrocytes influence neurocognitive function through their involvement in the uptake and release of gliotransmitters, modulation of inflammatory mediators, and metabolic regulation. These processes have been implicated in various neurodegenerative and neurocognitive disorders, including epilepsy, Alzheimer's disease, postoperative cognitive dysfunction, and sepsis-associated encephalopathy. Given the emerging role of astrocytes in these conditions, understanding the mechanisms by which they modulate neurocognitive function is essential for identifying potential therapeutic targets. This review provides an overview of the current understanding of astrocytic contributions to neurocognitive dysfunction and explores the therapeutic opportunities provided by the targeting of astrocyte-mediated pathways.