Neural Stem Cell-Derived Astrogliogenesis: The Hidden Player of the Adult Hippocampal Cytogenic Niche

Abstract

The adult mammalian brain exhibits remarkable forms of neural plasticity, enabling it to adapt and reorganize in response to internal and external stimuli. These plastic mechanisms include cytogenesis, the capacity of producing new neuronal and glial cells in restricted brain regions through processes known as neuro- and gliogenesis, respectively. Although many advances have been made in understanding adult brain plastic processes associated with cell genesis, as well as its functional and behavioral implications, most of the evidence is focused on neuronal cells. Even though astrocytes play a critical role in maintaining a neurochemical and electrophysiological homeostasis in the brain and provide a pivotal support to neuronal activity, the molecular mechanisms underlying the formation and functional integration of newly formed astroglial cells are poorly understood. However, some studies have provided key insights into the molecular mechanisms driving the generation of adult neural stem cell (NSC)-derived astrocytes, focusing on the dentate gyrus of the hippocampal cytogenic niche. Recent work has demonstrated that intrinsic and extrinsic factors can modulate astrogliogenesis. In the context of neuropathogenesis, this mechanism may be compromised in the hippocampus, contributing to functional and behavioral impairments. Here, we review the mechanisms underlying NSC-derived hippocampal astrogliogenesis, examining current perspectives on how adult-born astrocytes develop in the adult brain, their functional relevance, and the intricate regulation of the astrogliogenic process.