Abstract
Adult neurogenesis, involving the generation of functional neurons from adult neural stem cells (NSCs), occurs constitutively in discrete brain regions such as hippocampus, sub-ventricular zone (SVZ) and hypothalamus. The intrinsic structural plasticity of the neurogenic process allows the adult brain to face the continuously changing external and internal environment and requires coordinated interplay between all cell types within the specialized microenvironment of the neurogenic niche. NSC-, neuronal- and glia-derived factors, originating locally, regulate the balance between quiescence and self-renewal of NSC, their differentiation programs and the survival and integration of newborn cells. Extracellular Vesicles (EVs) are emerging as important mediators of cell-to-cell communication, representing an efficient way to transfer the biologically active cargos (nucleic acids, proteins, lipids) by which they modulate the function of the recipient cells. Current knowledge of the physiological role of EVs within adult neurogenic niches is rather limited. In this review, we will summarize and discuss EV-based cross-talk within adult neurogenic niches and postulate how EVs might play a critical role in the regulation of the neurogenic process.
Highlights
It is commonly accepted that discrete regions of the adult mammalian brain host neural stem cells that divide in situ and give rise to new neurons, a phenomenon referred to as “adult neurogenesis”.The two most characterized neurogenic niches are the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), a brain region in which adult neurogenesis was confirmed in humans [1] and the subventricular zone (SVZ) of the lateral ventricles, whose relevance in adult human physiology is debated
These findings suggest the ability of Extracellular Vesicles (EVs) released by neural stem cells (NSCs) under inflammatory conditions to preferentially or selectively target astrocytes and microglia, given the largely documented evidence of IFN-γ signaling in both the cell types [75,76]
The limited number of studies describing the interaction between Neuron-derived EVs (NDEs) and glia hinders a comprehensive interpretation of this cross-talk within the adult neurogenic niche, the immunomodulatory potential of neuron-derived EVs may be relevant to a better understanding of glia-mediated regulation of the neurogenic process
Summary
It is commonly accepted that discrete regions of the adult mammalian brain host neural stem cells that divide in situ and give rise to new neurons, a phenomenon referred to as “adult neurogenesis”. Regardless of the neurogenic region and the underlying complex functions, under physiological conditions, each step of adult neurogenesis needs to be tightly controlled by both niche-derived signals and by extrinsic environmental cues, which, together, ensure appropriate rates of NSC proliferation, differentiation, migration, neurite extension and integration of newborn cells into preexisting circuits [10,11]. This extensive modulation underlies the functional plasticity that is intrinsic to the neurogenic process, by which the brain outcome can be optimized for the needs of a given environment and/or experience. Since several molecular constituents in EVs have been found to be associated with specific diseases and treatment responses, EVs may represent reliable biomarkers which could serve as a diagnostic tool [53]
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