Lucassen P, Meerlo P, Naylor A, van Dam A, Dayer A, Fuchs E et al. Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: Implications for depression and antidepressant action. Eur Neuropsychopharmacol 20: 1-17

Centre for Neuroscience, Swammerdam Institute of Life Sciences, University of Amsterdam, P.O. box 94214, 1090 GE Amsterdam, the Netherlands.
European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology (Impact Factor: 4.37). 09/2009; 20(1):1-17. DOI: 10.1016/j.euroneuro.2009.08.003
Source: PubMed


Adult hippocampal neurogenesis, a once unorthodox concept, has changed into one of the most rapidly growing fields in neuroscience. The present report results from the ECNP targeted expert meeting in 2007 during which cellular plasticity changes were addressed in the adult brain, focusing on neurogenesis and apoptosis in hippocampus and frontal cortex. We discuss recent studies investigating factors that regulate neurogenesis with special emphasis on effects of stress, sleep disruption, exercise and inflammation, a group of seemingly unrelated factors that share at least two unifying properties, namely that they all regulate adult hippocampal neurogenesis and have all been implicated in the pathophysiology of mood disorders. We conclude that although neurogenesis has been implicated in cognitive function and is stimulated by antidepressant drugs, its functional impact and contribution to the etiology of depression remains unclear. A lasting reduction in neurogenesis following severe or chronic stress exposure, either in adult or early life, may represent impaired hippocampal plasticity and can contribute to the cognitive symptoms of depression, but is, by itself, unlikely to produce the full mood disorder. Normalization of reductions in neurogenesis appears at least partly, implicated in antidepressant action.

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    • "Finally, and on a related note, it may be that there is not a direct relationship between reduction in neuroblast cells and the behaviors reported here, and that other intermediates are ultimately producing our behavioral changes. For example, changes in glia, inflammatory signals, or vasculature can augment the depressive-like phenotype[18,33,110,111]. While other ablation methods have side effects (i.e. "
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    ABSTRACT: Depression and anxiety involve hippocampal dysfunction, but the specific relationship between these mood disorders and adult hippocampal dentate gyrus neurogenesis remains unclear. In both humans with MDD and rodent models of depression, administration of antidepressants increases DG progenitor and granule cell number, yet rodents with induced ablation of DG neurogenesis typically do not demonstrate depressive- or anxiety-like behaviors. The conflicting data may be explained by the varied duration and degree to which adult neurogenesis is reduced in different rodent neurogenesis ablation models. In order to test this hypothesis we examined how a transient–rather than permanent–inducible reduction in neurogenesis would alter depressive- and anxiety-like behaviors. Transgenic Nestin-CreERT2/floxed diphtheria toxin fragment A (DTA) mice (Cre+DTA+) and littermates (Cre+DTA-; control) were given tamoxifen (TAM) to induce recombination and decrease nestin-expressing stem cells and their progeny. The decreased neurogenesis was transient: 12 days post-TAM Cre+DTA+ mice had fewer DG proliferating Ki67+ cells and fewer DCX+ neuroblasts/immature neurons relative to control, but 30 days post-TAM Cre+DTA+ mice had the same DCX+ cell number as control. This ability of DG neurogenesis to recover after partial ablation also correlated with changes in behavior. Relative to control, Cre+DTA+ mice tested between 12–30 days post-TAM displayed indices of a stress-induced anxiety phenotype–longer latency to consume highly palatable food in the unfamiliar cage in the novelty-induced hypophagia test, and a depression phenotype–longer time of immobility in the tail suspension test, but Cre+DTA+ mice tested after 30 days post-TAM did not. These findings suggest a functional association between adult neurogenesis and stress induced anxiety- and depressive-like behaviors, where induced reduction in DCX+ cells at the time of behavioral testing is coupled with stress-induced anxiety and a depressive phenotype, and recovery of DCX+ cell number corresponds to normalization of these behaviors.
    Full-text · Article · Jan 2016 · PLoS ONE
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    • "In contrast to the highly proliferative stem cells of the embryonic neural tube, NSCs in the postnatal and adult brain are relatively quiescent (Temple 2001; Niu et al. 2011; Fuentealba et al. 2012). Adult NSCs are stimulated to divide by diverse physiological stimuli, including physical exercise and cognitive stimulation, while conversely, stress, anxiety, and old age suppress their divisions (Fabel and Kempermann 2008; Ma et al. 2009; Lucassen et al. 2010). Seizures stimulate NSC divisions in aged mice, suggesting that this cell cycle arrest is reversible (Lugert et al. 2010). "

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    • "(3) non-stressful contextual learning in an object recognition task (ORT, Bevins and Besheer, 2006) and an object-in-location task (OLT, adapted from Ennaceur et al., 2005). Hippocampal structural measures included dentate gyrus (DG) volume, proliferation and neurogenesis that can be altered by (early life) stress and are involved in aspects of cognition (Lucassen et al., 2010, 2013; Oomen et al., 2011, 2014). The peripubertal period is considered a critical time window in which programming of the brain and HPA axis can be primed or ameliorated, depending on the intervention (Tsoory and Richter-Levin, 2006). "
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    ABSTRACT: We tested the effect of early life stress (ELS) - 24 h maternal deprivation at postnatal day 3 - on cognitive performance and hippocampal structure in 12-17 weeks old female rats. Behavioral performance was examined in: the elevated plus maze, as an index for general anxiety; the rodent Iowa gambling test, probing reward-based decision making; and the object recognition and object-in-location task, to assess non-stressful contextual memory performance. We further determined hippocampal dentate gyrus volume and cell density as well as adult proliferation and neurogenesis rates. Half of the rats was treated with the glucocorticoid receptor antagonist mifepristone during a critical pre-pubertal developmental window (postnatal days 26-28), in an attempt to ameliorate the potentially adverse behavioral consequences of ELS. Neither maternal deprivation nor treatment with the glucocorticoid antagonist affected behavioral performance of the females in any of the tasks. Also, dentate gyrus structure, proliferation and neurogenesis were not different between the groups. The lack of structural differences and a behavioral phenotype in non-stressful hippocampus dependent learning tasks fits with the lack of phenotype generally reported after ELS in female but less so in male rodents. As evident from an extensive literature review, female and male animals appear to respond more similarly to early life adversity when tested in anxiety-related tasks. This agrees with recent findings in humans suggesting that females may be relatively resilient to the structural / hippocampal effects of childhood maltreatment, but not to the anxiety and mood-related psychopathology for which childhood maltreatment is considered a risk factor. Copyright © 2015. Published by Elsevier Ltd.
    No preview · Article · Aug 2015 · Neuroscience
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