Neural Stem Cells and Nutrients: Poised Between Quiescence and Exhaustion

Quiescent stem cells, including quiescent neural stem cells (qNSC), recapitulate many aspects of hypometabolic, reversibly growth-arrested, and long-lived states of simple organisms. Nutrient signals and energy metabolism control adult neurogenesis at different levels, and in particular regulate NSC transition between quiescent and activated states. Converging evidence from genetic and nutritional studies indicate that deregulated nutrient signaling leads to abnormal and wasteful NSC activation followed by premature exhaustion. NSC exhaustion is a major component of brain aging and related disease, and may explain the connection between metabolic disorders and cognitive impairment. Adult neurogenesis initiated by neural stem cells (NSCs) contributes to brain homeostasis, damage repair, and cognition. Energy metabolism plays a pivotal role in neurogenic cell fate decisions regarding self-renewal, expansion and multilineage differentiation. NSCs need to fine-tune quiescence and proliferation/commitment to guarantee lifelong neurogenesis and avoid premature exhaustion. Accumulating evidence supports a model whereby calorie restriction or increased energy expenditure reinforce NSC quiescence and promote self-renewal. Conversely, growth/proliferation inputs and anabolic signals, although necessary for neurogenesis, deplete the NSCs pool in the long run. This framework incorporates the emerging neurogenic roles of nutrient-sensing signaling pathways, providing a rationale for the alarming connection between nutritional imbalances, metabolic disorders and accelerated brain aging. Adult neurogenesis initiated by neural stem cells (NSCs) contributes to brain homeostasis, damage repair, and cognition. Energy metabolism plays a pivotal role in neurogenic cell fate decisions regarding self-renewal, expansion and multilineage differentiation. NSCs need to fine-tune quiescence and proliferation/commitment to guarantee lifelong neurogenesis and avoid premature exhaustion. Accumulating evidence supports a model whereby calorie restriction or increased energy expenditure reinforce NSC quiescence and promote self-renewal. Conversely, growth/proliferation inputs and anabolic signals, although necessary for neurogenesis, deplete the NSCs pool in the long run. This framework incorporates the emerging neurogenic roles of nutrient-sensing signaling pathways, providing a rationale for the alarming connection between nutritional imbalances, metabolic disorders and accelerated brain aging. orexigenic neuropeptides released by AgRP/NPY neurons that reside in the arcuate nucleus of the hypothalamus. trophic and pro-neurogenic factor belonging to the neurotrophin family of growth factors. They act on several neurons of the central and peripheral nervous system. reduction of calorie intake without malnutrition. the main inhibitory neurotransmitter of mammalian CNS. a repressor-type basic helix-loop-helix (bHLH) transcriptional factor repressing genes that require a bHLH protein for their transcription. a polypeptide hormone with high sequence similarity to insulin. IGF-I is produced by the liver in proportion to systemic availability of amino acids. a serine/threonine kinase and the catalytic subunit of two distinct molecular complexes, mTORC1 and mTORC2, the first of which is specifically involved in amino acid and energy sensing and is inhibited by rapamycin. free-floating cell clusters generated in vitro by neural stem cells and comprising NSCs and their progeny. Neurosphere assay (NSA) provides a method to evaluate the frequency and self-renewal capacity of NSCs based on the number and size of neurospheres formed by seeding a dissociated neurogenic tissue in a highly defined, growth factor-enriched medium. ionotropic glutamate receptors largely expressed in the CNS. enzymes that assemble on the membrane of phagocytic and nonphagocytic cells in response to external stimuli to generate superoxide (O2ˉ) by incomplete reduction of molecular oxygen. a cell state characterized by cell cycle arrest, enhanced stress resistance, extended longevity and reduced transcriptional, translational and metabolic activity. a family of proteins with mono-ADP-ribosyltransferase or deacylase activity that orchestrate cell and tissue adaptation to different kinds of stressful conditions, including nutrient restriction, through a host of genetic and epigenetic mechanisms. experience-dependent change in the efficacy of synaptic transmission that underlies learning and memory formation. The best-studied forms of synaptic plasticity are long-term potentiation (LTP) and long-term depression (LTD), namely the activity-dependent strengthening and weakening of synapses, respectively. also known as neural progenitor cells (NPC), are differentiation committed cells derived from the asymmetric division of stem cells and endowed by elevated proliferative but no self-renewal capacity.