Article

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: 1.62). 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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    • "Current evidence indicates that continuous neurogenesis takes place during development of neural system and processes of generation and maturation of neurons extend to adulthood [3]. Many factors influence adult brain neurogenesis such as hormones, growth factors, and neurotransmitters [4]. Newly generated neurons form initial neurites which differentiate into long-distance projections called axons or into multiple short length dendrites. "
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    ABSTRACT: The hypothalamus is a source of neural progenitor cells which give rise to different populations of specialized and differentiated cells during brain development. Newly formed neurons in the hypothalamus can synthesize and release various neuropeptides. Although term neuropeptide recently undergoes redefinition, small-size hypothalamic neuropeptides remain major signaling molecules mediating short- and long-term effects on brain development. They represent important factors in neurite growth and formation of neural circuits. There is evidence suggesting that the newly generated hypothalamic neurons may be involved in regulation of metabolism, energy balance, body weight, and social behavior as well. Here we review recent data on the role of hypothalamic neuropeptides in adult neurogenesis and neuritogenesis with special emphasis on the development of food intake and social behavior related brain circuits.
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    • "Age has been related with less capacity to produce neurogenesis [45] and with different progenitor cell responses [9], although healthy elderly subjects have been shown to be capable of improving CPC clonogenic and migratory capacity after exercise [9]. In this regard, it should be noted that the subjects recruited for the present research were much younger than the four subjects included in our previous study [29]. "
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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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