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


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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    ABSTRACT: Background Our goal was to test whether short-term intermittent hypobaric hypoxia (IHH) at a level well tolerated by healthy humans could, in combination with muscle electro-stimulation (ME), mobilize circulating progenitor cells (CPC) and increase their concentration in peripheral circulation. Methods Nine healthy male subjects were subjected, as the active group (HME), to a protocol involving IHH plus ME. IHH exposure consisted of four, three-hour sessions at a barometric pressure of 540 hPa (equivalent to an altitude of 5000 m). These sessions took place on four consecutive days. ME was applied in two separate 20-minute periods during each IHH session. Blood samples were obtained from an antecubital vein on three consecutive days immediately before the experiment, and then 24 h, 48 h, 4 days, 7 days and 14 days after the last day of hypoxic exposure. Four months later a control study was carried out involving seven of the original subjects (CG), who underwent the same protocol of blood samples but without receiving any special stimulus. Results In comparison with the CG the HME group showed only a non-significant increase in the number of CPC CD34+ cells on the fourth day after the combined IHH and ME treatment. Conclusion CPC levels oscillated across the study period and provide no firm evidence to support an increased CPC count after IHH plus ME, although it is not possible to know if this slight increase observed is physiologically relevant. Further studies are required to understand CPC dynamics and the physiology and physiopathology of the hypoxic stimulus.
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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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    ABSTRACT: Stress hormones are strong modulators of brain activity. Given the adaptive nature of stress, hormones released during stress response influence a myriad of brain phenomena including development, plasticity, neurogenesis, homeostasis, central immune response and cognition. In addition to the well-known role of neurons in the stress-brain interaction, glial cells have recently become crucial for the knowledge of this topic. Glial cells are viewed now as important as neurons for the normal function of the brain. There is a growing body of knowledge showing that glial cells crucially affect brain development, homeostasis, synaptic
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