Abstract
Newborn neurons in the adult hippocampus are regulated by many intrinsic and extrinsic cues. It is well accepted that elevated glucocorticoid levels lead to downregulation of adult neurogenesis, which this review discusses as one reason why psychiatric diseases, such as major depression, develop after long-term stress exposure. In reverse, adult neurogenesis has been suggested to protect against stress-induced major depression, and hence, could serve as a resilience mechanism. In this review, we will summarize current knowledge about the functional relation of adult neurogenesis and stress in health and disease. A special focus will lie on the mechanisms underlying the cascades of events from prolonged high glucocorticoid concentrations to reduced numbers of newborn neurons. In addition to neurotransmitter and neurotrophic factor dysregulation, these mechanisms include immunomodulatory pathways, as well as microbiota changes influencing the gut-brain axis. Finally, we discuss recent findings delineating the role of adult neurogenesis in stress resilience.
Highlights
Adult Neurogenesis10.3390/ijms22147339Adult neurogenesis in the mammalian brain is a continuous lifelong physiological process, which dramatically declines during aging [1]
The results further suggest that the mere numbers of newborn neurons are a relatively coarse read-out, and their neuronal activity and degree of functional integration into the existing neuronal network of the mature dentate gyrus (DG) is a crucial factor in governing resilience
The above mentioned contradicting results could have been due to experimental reasons by using different stress paradigms and neurogenesis ablation protocols, as well as distinct behavioral readouts
Summary
Adult neurogenesis in the mammalian brain is a continuous lifelong physiological process, which dramatically declines during aging [1]. The main work, so far, elucidating the regulatory mechanisms of adult neural stem cells has been done in rodent animal models, whereas the existence of neurogenesis in the adult human brain is still under debate [2,3,4]. Even if many studies report the existence of adult neurogenesis in humans during the whole lifespan [5,6,7,8,9,10], these findings have been questioned by others, which could detect adult neural stem cells and their progeny only in early childhood [11,12,13]. A direct comparison to rodent models seems difficult as brains from healthy human subjects cannot be processed and analyzed to rodents, since human samples usually arise from postmortem fixed tissue [16]. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
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