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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Available from: Paul J Lucassen, Sep 30, 2015
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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). "
    • "(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.
    Neuroscience 08/2015; DOI:10.1016/j.neuroscience.2015.08.024 · 3.36 Impact Factor
    • "So far, the effects of the chronic ES model have been mainly accredited to the altered sensory stimuli from the mother (Fenoglio et al., 2006; Ivy et al., 2008; Rice et al., 2008) and the altered levels of stress hormones (Liu et al., 1997; Weaver et al., 2004; Ivy et al., 2008) and stress related neuropeptides (Rice et al., 2008; Murgatroyd et al., 2009; Korosi et al., 2010; Chen et al., 2012). There is an abundance of literature about the regulating role of CORT on neurogenesis (Lucassen et al., 2010), even though that is in most cases referring to the effects of CORT in adulthood and mostly pointing to an inhibitory role of CORT on the neurogenic process. Whether the rise in CORT that we observe at P9 (and no longer in adulthood) modulates the neurogenesis process longterm remains to be determined. "
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    ABSTRACT: Clinical and pre-clinical studies have shown that early-life adversities, such as abuse or neglect, can increase the vulnerability to develop psychopathologies and cognitive decline later in life. Remarkably, the lasting consequences of stress during this sensitive period on the hypothalamic-pituitary-adrenal axis and emotional function closely resemble the long-term effects of early malnutrition and suggest a possible common pathway mediating these effects. During early-life, brain development is affected by both exogenous factors, like nutrition and maternal care as well as by endogenous modulators including stress hormones. These elements, while mostly considered for their independent actions, clearly do not act alone but rather in a synergistic manner. In order to better understand how the programming by early-life stress takes place, it is important to gain further insight into the exact interplay of these key elements, the possible common pathways as well as the underlying molecular mechanisms that mediate their effects. We here review evidence that exposure to both early-life stress and early-life under-/malnutrition similarly lead to life-long alterations on the neuroendocrine stress system and modify emotional functions. We further discuss how the different key elements of the early-life environment interact and affect one another and next suggest a possible role for the early-life adversity induced alterations in metabolic hormones and nutrient availability in shaping later stress responses and emotional function throughout life, possibly via epigenetic mechanisms. Such knowledge will help to develop intervention strategies, which gives the advantage of viewing the synergistic action of a more complete set of changes induced by early-life adversity.
    Stress (Amsterdam, Netherlands) 08/2015; · 2.72 Impact Factor
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