Research update: Neurogenesis in adult brain and neuropsychiatric disorders

Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA.
Mount Sinai Journal of Medicine A Journal of Translational and Personalized Medicine (Impact Factor: 1.56). 12/2006; 73(7):931-40.
Source: PubMed

ABSTRACT Until recently neurogenesis in mammals was considered to occur only during the embryonic and early post-natal periods and to have no significant role in the adult nervous system. However, it is now accepted that neurogenesis occurs in two brain regions in adult mammals, namely, the hippocampus and olfactory bulb. In both regions new neurons arise from a resident population of neural progenitor cells that are maintained throughout adult life. Hippocampal neurogenesis is required for some types of hippocampal-dependent learning. Many factors enhance hippocampal neurogenesis including hormones, growth factors, drugs, neurotransmitters, and physical exercise as well as learning a hippocampal-dependent task. Other factors suppress hippocampal neurogenesis; these include aging, stress, glucocorticoids and stimuli that activate the pituitary/adrenal axis. Recently much attention has become focused on the relevance of hippocampal neurogenesis to the pathophysiology and treatment of mood disorders. Indeed all major pharmacological and non-pharmacological treatments for depression enhance hippocampal neurogenesis and suppressing hippocampal neurogenesis in mice blocks behavioral responses in some antidepressant-sensitive tests. Altered hippocampal neurogenesis may also play a pathophysiological role in neurodegenerative disorders such as Alzheimer's disease. How much neurogenesis occurs normally in other brain regions is unclear. Neural progenitors are found throughout the neuraxis including both neurogenic and non-neurogenic regions. When cultured in vitro or isolated and transplanted back into neurogenic brain regions, these cells can differentiate into neurons although in their in situ location they seem to behave as lineage-restricted glial progenitors. The environmental cues that limit the potential of progenitor cells in non-neurogenic brain regions are unknown. However, an emerging view is that astrocytes, a subset of which also functions as neural progenitor cells, are critical in regulating the local environment. After transplantation into adult brain, neural stem cells are capable of surviving and differentiating into both neurons and glial cells, offering hope that stem cell therapy may be utilized to treat a variety of neurological and perhaps psychiatric disorders. The widespread existence of endogenous neural progenitors even in non-neurogenic brain regions also offers hope that the potential of these cells may be harnessed to repair cellular injuries caused by injuries such as stroke, trauma or neurodegenerative diseases. While obstacles remain to both approaches, stem-cell-based therapies remain an area of intense research interest.

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Available from: Rita de gasperi, Aug 22, 2015
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    • "Studies demonstrating hippocampal shrinkage have also demonstrated amygdala hypertrophy and loss of dendritic spines in prefrontal cortex (McLaughlin, Gomez, Baran, & Conrad, 2007; Vyas, Mitra, Shankaranarayana F. Jauregui-Huerta 1 , A. Uribe Gonzalez 1 , J. Garcia-Estrada et al. 6 Rao, & Chattarji, 2002). Controversy exists however on whether these changes are caused by inhibition of neurogenesis, dendritic shrinkage or other mechanisms (Banasr, et al., 2008; Elder, De Gasperi, & Gama Sosa, 2006; Jauregui-Huerta, Ruvalcaba-Delgadillo, Gonzalez-Castaneda, et al., 2010). Thus far, the consistent finding of glial cell changes into the altered hippocampal and/or prefrontal cortex of stressed subjects placed these extraordinary cells in the eye of stress specialists. "
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    • "Another potential mechanism is the actual generation of new hippocampal neurons (neurogenesis). Although neurogenesis was initially thought to occur only during embryonic and early postnatal development, a large body of evidence now confirms that new neurons are generated throughout life from neural progenitor cells within specific brain regions, including the hippocampus [Elder et al., 2006; Eriksson, 2003; Eriksson et al., 1998; Gage, 2002]. "
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    ABSTRACT: Studies linking meditation and brain structure are still relatively sparse, but the hippocampus is consistently implicated as one of the structures altered in meditation practitioners. To explore hippocampal features in the framework of meditation, we analyzed high-resolution structural magnetic resonance imaging data from 30 long-term meditators and 30 controls, closely matched for sex, age, and handedness. Hippocampal formations were manually traced following established protocols. In addition to calculating left and right hippocampal volumes (global measures), regional variations in surface morphology were determined by measuring radial distances from the hippocampal core to spatially matched surface points (local measures). Left and right hippocampal volumes were larger in meditators than in controls, significantly so for the left hippocampus. The presence and direction of this global effect was confirmed locally by mapping the exact spatial locations of the group differences. Altogether, radial distances were larger in meditators compared to controls, with up to 15% difference. These local effects were observed in several hippocampal regions in the left and right hemisphere though achieved significance primarily in the left hippocampal head. Larger hippocampal dimensions in long-term meditators may constitute part of the underlying neurological substrate for cognitive skills, mental capacities, and/or personal traits associated with the practice of meditation. Alternatively, given that meditation positively affects autonomic regulation and immune activity, altered hippocampal dimensions may be one result of meditation-induced stress reduction. However, given the cross-sectional design, the lack of individual stress measures, and the limited resolution of brain data, the exact underlying neuronal mechanisms remain to be established. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
    Human Brain Mapping 12/2013; 34(12). DOI:10.1002/hbm.22153 · 6.92 Impact Factor
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    • "No difference in NPC proliferation or neurogenesis in FAD mutants Enrichment-induced NPC proliferation and neurogenesis less in FAD mutants Choi et al. (2008) Brain Struct Funct (2010) 214:127–143 135 neurogenesis is required for some types of hippocampusdependent learning and neurogenesis is also enhanced by learning a hippocampus-dependent task (Elder et al. 2006), suggesting that impaired hippocampal neurogenesis might contribute to AD related memory dysfunction and constitute a therapeutic target. Pathologically, the hippocampus is affected early in AD with pyramidal cell loss and disruption of perforant path connections from the entorhinal cortex to the dentate granule cell layer (Hyman et al. 1984; Hof et al. 2003). "
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    ABSTRACT: Mutations in presenilin-1 (PS1) and presenilin-2 (PS2) cause familial Alzheimer’s disease (FAD). Presenilins influence multiple molecular pathways and are best known for their role in the γ-secretase cleavage of type I transmembrane proteins including the amyloid precursor protein (APP). PS1 and PS2 FAD mutant transgenic mice have been generated using a variety of promoters. PS1-associated FAD mutations have also been knocked into the endogenous mouse gene. PS FAD mutant mice consistently show elevations of Aβ42 with little if any effect on Aβ40. When crossed with plaque forming APP FAD mutant lines, the PS1 FAD mutants cause earlier and more extensive plaque deposition. Although single transgenic PS1 or PS2 mice do not form plaques, they exhibit a number of pathological features including age-related neuronal and synaptic loss as well as vascular pathology. They also exhibit increased susceptibility to excitotoxic injury most likely on the basis of exaggerated calcium release from the endoplasmic reticulum. Electrophysiologically long-term potentiation in the hippocampus is increased in young PS1 FAD mutant mice but this effect appears to be lost with aging. In most studies neurogenesis in the adult hippocampus is also impaired by PS1 FAD mutants. Mice in which PS1 has been conditionally knocked out in adult forebrain on a PS2 null background (PS1/2 cDKO) develop a striking neurodegeneration that mimics AD neuropathology in being associated with neuronal and synaptic loss, astrogliosis and hyperphosphorylation of tau, although it is not accompanied by plaque deposits. The relevance of PS transgenic mice as models of AD is discussed.
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