Stress, hippocampal neurogenesis and cognition: functional correlations

Abstract

The brain of many species including humans, harbors stem cells that continue to generate new neurons up into adulthood. This form of structural plasticity occurs in a limited number of brain regions, i.e. the subventricular zone and the hippocampal dentate gyrus and is regulated by environmental and hormonal factors. In this minireview, we provide an overview of the effects of stress and glucocorticoid hormones on adult hippocampal neurogenesis and discuss how these effects may be relevant for cognitive function and possibly, brain disease. While its exact functional role remains elusive, adult neurogenesis has been implicated in learning and memory, fear and mood regulation and recently, adult-born neurons were found to be involved in specific cognitive functions such as pattern separation (i.e. the ability to form unique memory representations) and cognitive flexibility. The process of adult neurogenesis is influenced by several factors; whereas e.g. exercise stimulates, exposure to stress and stress hormones generally inhibit neurogenesis. Effects of acute, mild stress are generally short-lasting and recover quickly, but chronic or severe forms of stress can induce lasting reductions in adult neurogenesis. Some of the inhibitory effects of stress can be rescued by exercise, by allowing a period of recovery from stress, by drugs that target the stress system, or by some, but not all, antidepressants. Stress may, partly through its effects on adult neurogenesis, alter structure and plasticity of the hippocampal circuit. This can lead to subsequent changes in stress responsivity and aspects of memory processing, which may be particularly relevant for stress related psychopathology or brain diseases that involve perturbed memory processing.

Keywords

adult neurogenesis / stem cells / hippocampus / stress / memory / pattern separation / cognition

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Acknowledgments

PJL is supported by the HersenStichting Nederland, Alzheimer Nederland, ISAO, NWO and Amsterdam Brain & Cognition (ABC), CAO is supported by the Amsterdam Brain and Mind Project (ABMP).

Compliance with ethics guidelines

Paul J. Lucassen and Charlotte A. Oomen declare that they have no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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