Adult Neurogenesis, Mental Health, and Mental Illness: Hope or Hype?

Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 12/2008; 28(46):11785-91. DOI: 10.1523/JNEUROSCI.3798-08.2008
Source: PubMed


Psychiatric and neurologic disorders take an enormous toll on society. Alleviating the devastating symptoms and consequences of neuropsychiatric disorders such as addiction, depression, epilepsy, and schizophrenia is a main force driving clinical and basic researchers alike. By elucidating these disease neuromechanisms, researchers hope to better define treatments and preventive therapies. Research suggests that regulation of adult hippocampal neurogenesis represents a promising approach to treating and perhaps preventing mental illness. Here we appraise the role of adult hippocampal neurogenesis in major psychiatric and neurologic disorders within the essential framework of recent progress made in understanding "normal" adult neurogenesis. Topics addressed include the following: the life cycle of an adult hippocampal stem cell and the implications for aging; links between learning and hippocampal neurogenesis; the reciprocal relationship between cocaine self-administration and adult hippocampal neurogenesis; the role of adult neurogenesis in an animal model of depression and response to antidepressant exposure; the impact of neonatal seizures on dentate gyrus neurogenesis; and the contribution of a schizophrenia-susceptibility gene to adult hippocampal neurogenesis. These topics are discussed in light of the regulation of adult neurogenesis, the relationship to normal neurogenesis in adulthood and aging, and, importantly, the manipulation of neurogenesis to promote mental health and treat mental illness.

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Available from: Leslie Meltzer, Jul 16, 2014
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    • "Interestingly, repeated stress has limited effects on anxiety-like behavior and depressive-like behavior in the pregnant female (Baker et al., 2008; Pawluski et al., 2015; Pawluski et al., 2011), suggesting differential effects on affective behaviors during pregnancy and lactation. Stress also affects hippocampal neurogenesis, and alterations in hippocampal neurogenesis play a role in both anxiety-and depressive-like behaviors (Eisch et al., 2008; Wainwright and Galea, 2013). In adult virgin female rats, the effects of stress on hippocampal neurogenesis appear to be dependent on the duration of the stress and the age of the new surviving cells [for review see (Pawluski et al., 2009)]. "
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    ABSTRACT: It is becoming clear that the female brain has an inherent plasticity that is expressed during reproduction. The changes that occur benefit the offspring, which in turn secures the survival of the mother's genetic legacy. Thus, the onset of maternal motivation involves basic mechanisms from genetic expression profiles, to hormone release, to hormone-neuron interactions, all of which fundamentally change the neural architecture - and for a period of time that extends, interestingly, beyond the reproductive life of the female. Although multiple brain areas involved in maternal responses are discussed, this review focuses primarily on plasticity in the maternal hippocampus during pregnancy, the postpartum period and well into aging as it pertains to changes in cognition. In addition, the effects of prolonged and repeated stress on these dynamic responses are considered. The maternal brain is a marvel of directed change, extending into behaviors both obvious (infant-directed) and less obvious (predation, cognition). In sum, the far-reaching effects of reproduction on the female nervous system provide an opportunity to investigate neuroplasticity and behavioral flexibility in a natural mammalian model. Copyright © 2015. Published by Elsevier Inc.
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    • "The problem of relations between adult neurogenesis and pathogenesis or/and course of psychiatric diseases like bipolar disorder (Walton et al. 2012; Braun and Jessberger 2014), schizophrenia (Reif et al. 2007; Eisch et al. 2008; Christian et al. 2010; DeCarolis and Eisch 2010; de Koning et al. 2013), anxiety disorders (Kheirbek et al. 2012), and particularly depression (Krishnan and Nestler 2008; Lucassen et al. 2010; Mahar et al. 2014) is currently broadly discussed. Experiments on animal models have proven that elevated levels of stress hormones, observed in depression, often correlated with neurogenesis process reduction. "
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    ABSTRACT: The discovery of undifferentiated, actively proliferating neural stem cells (NSCs) in the mature brain opened a brand new chapter in the contemporary neuroscience. Adult neurogenesis appears to occur in specific brain regions (including hypothalamus) throughout vertebrates' life, being considered an important player in the processes of memory, learning, and neural plasticity. In the adult mammalian brain, NSCs are located mainly in the subgranular zone (SGZ) of the hippocampal dentate gyrus and in the subventricular zone (SVZ) of the lateral ventricle ependymal wall. Besides these classical regions, hypothalamic neurogenesis occurring mainly along and beneath the third ventricle wall seems to be especially well documented. Neurogenic zones in SGZ, SVZ, and in the hypothalamus share some particular common features like similar cellular cytoarchitecture, vascularization pattern, and extracellular matrix properties. Hypothalamic neurogenic niche is formed mainly by four special types of radial glia-like tanycytes. They are characterized by distinct expression of some neural progenitor and stem cell markers. Moreover, there are numerous suggestions that newborn hypothalamic neurons have a significant ability to integrate into the local neural pathways and to play important physiological roles, especially in the energy balance regulation. Newly formed neurons in the hypothalamus can synthesize and release food intake regulating neuropeptides and they are sensitive to the leptin. On the other hand, high-fat diet positively influences hypothalamic neurogenesis in rodents. The nature of this intriguing new site of adult neurogenesis is still so far poorly studied and requires further investigations.
    Full-text · Article · Apr 2014 · Cellular and Molecular Neurobiology
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    • "A vast array of experimental studies suggested that adult hippocampal neurogenesis may be altered in various neuropsychiatric and neurodegenerative disorders [20] [21] [22] [23] [24] [25], where its disregulation may contribute to cognitive impairment and/or emotional aspects of those diseases. "
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    ABSTRACT: Adult hippocampal neurogenesis is a peculiar form of process of neuroplasticity that in recent years has gained great attention for its potential implication in cognition and in emotional behavior in physiological conditions. Moreover, a vast array of experimental studies suggested that adult hippocampal neurogenesis may be altered in various neuropsychiatric disorders, including major depression, where its disregulation may contribute to cognitive impairment and/or emotional aspects associated with those diseases. An intriguing area of interest is the potential influence of drugs on adult neurogenesis. In particular, several psychoactive drugs, including antidepressants, were shown to positively modulate adult hippocampal neurogenesis. Among molecules which could regulate adult hippocampal neurogenesis the NF- κ B family of transcription factors has been receiving particular attention from our and other laboratories. Herein we review recent data supporting the involvement of NF- κ B signaling pathways in the regulation of adult neurogenesis and in the effects of drugs that are endowed with proneurogenic and antidepressant activity. The potential implications of these findings on our current understanding of the process of adult neurogenesis in physiological and pathological conditions and on the search for novel antidepressants are also discussed.
    Full-text · Article · Feb 2014
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