Integration of Metabolic Pathways and Micronutrient Signals Influences Neurodevelopment by Modulating Neural Stem Cell Dynamics.

Central nervous system (CNS) development commences in third week of gestation with neural stem cells (NSCs), which, through symmetric division, expand the pool of stem cells and generate diverse types of neuronal and glia cells of CNS via asymmetric division. During neurodevelopment, spatiotemporal coordination is fundamental for appropriate morphogenesis and producing neuronal connections. Besides gene regulatory networks, external and internal factors guide NSCs during self-renewal, fate determination and differentiation. Recent studies indicate metabolism as one of the common converging integrators in NSCs to trigger modifications in response to external factors. One such external factor is micronutrients that profoundly affect different stages of neurodevelopment, including, differentiation, neural migration and maturation. This review aims to provide a summary of recent insights into how metabolism and micronutrients regulate different events of neurodevelopment including proliferation, fate determination and differentiation. Notably, we focus on illustrating the implications of mitochondria as key determinants of NSC fate and functionality. We also highlight the recent development on how metabolism orchestrates the epigenome of NSCs during proliferation and differentiation. We further explore the role of nutraceuticals in mitigating the risk of neurodevelopmental and adult neurological disorders, highlighting recent innovations in their therapeutic applications. An in-depth grasp of these molecular processes is fundamental to improving translational strategies for treating neurological disorders.