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Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus. Neurobiology of Aging, 27(10), 1505-1513

Max Delbrück Center for Molecular Medicine, Berlin-Buch, Robert-Rössle-Str. 10, 13125 Berlin, Germany.
Neurobiology of aging (Impact Factor: 4.85). 11/2006; 27(10):1505-13. DOI: 10.1016/j.neurobiolaging.2005.09.016
Source: PubMed

ABSTRACT Physical activity induces adult hippocampal neurogenesis. We here show that the acute up-regulating effect of voluntary wheel running on precursor cell proliferation decreases with continued exercise, but that continued exercise reduces the age-dependent decline in adult neurogenesis. Cell proliferation peaked at 3 days of running. After 32 days of exercise this response returned to baseline. Running-induced proliferation of transiently amplifying progenitor cells led to a consecutive increase in the number of more mature cells. Increasing age reduced adult neurogenesis at 9 months to 50% of the value at 6 weeks and to 17% at the age of 2 years. At both 1 and 2 years, precursor cell divisions remained inducible by physical activity. Exercise from 3 to 9 months of age significantly reduced the age-dependent decline in cell proliferation but (presumably in the absence of additional stimuli) did not maintain net neurogenesis at levels corresponding to a younger age. We propose that physical activity might contribute to successful aging by increasing the potential for neurogenesis represented by the pool of proliferating precursor cells.

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    • "In rodents, this type of exercise has also been related to increased cell proliferation in the hippocampus, and selective increases in cerebral blood volume, which is related to reduction in age-related decline in cell proliferation, and neurogenesis in the dentate gyrus (e.g. Kronenberg et al., 2006; Pereira et al., 2014; Van Praag et al., 2005). "
    The Preservation of Memory: Theory and Practice for Clinical and Non-Clinical Populations, Edited by Bruno D, 01/2015: chapter The effects of ageing and exercise on recollection and familiarity based memory processes.; Psychology Press: Taylor and Francis..
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    • "st stimulus for adult hippocampal neurogenesis in rodents from birth to the oldest age ( Kannangara et al . , 2011 ; Kronenberg et al . , 2003 ; Marlatt et al . , 2012 ; Steiner et al . , 2008 ; van Praag et al . , 2005 , 1999 ; Wu et al . , 2008 ) . Running has the potential to limit the massive decrease in neurogenesis observed in aged animals ( Kronenberg et al . , 2006 ) , an action which seems directly linked to the stimulation of NPC proliferation ( Kronenberg et al . , 2003 ; Lugert et al . , 2010 ; Steiner et al . , 2008 ) and / or shortening of cell cycle length ( Farioli - Vecchioli et al . , 2014 ) . Housing rodents in enriched environments has also been shown to increase hippocampal neurogenes"
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    ABSTRACT: Adult hippocampal neurogenesis drastically diminishes with age but the underlying mechanisms remain unclear. Here, age-related influences on the hippocampal early neuroprogenitor cell (NPC) pool was examined by quantifying changes in Sox1-expressing cells in the dentate gyrus (DG) subgranular zone from early adulthood (3 months) to middle age (12 months). Proliferation of distinct NPC subpopulations (Sox1+, Nestin+ and Doublecortin+) and newborn cell survival were also investigated. Examination of total BrdU+ and Doublecortin+ (DCX) cells revealed an early and dramatic age-dependent decline of hippocampal neurogenesis. Increasing age from 3 to 12 months was primarily associated with reduced total proliferation, in vivo (-79% of BrdU+ cells) but not in vitro, and DCX+ cell numbers (-89%). When proliferative rates of individual NPC subpopulations were examined, a different picture emerged as proliferating Nestin+ neuroprogenitors (-95% at 9 months) and BrdU+/DCX+ neuroblasts/immature neurons (-83% at 12 months) declined the most, while proliferating Sox1+ NPCs only dropped by 53%. Remarkably, despite greatly reduced proliferative rates and recent reports of Nestin+ neuroprogenitor loss, total numbers of early Sox1+ NPCs were unaffected by age (at least up to middle age) and newborn cell survival within the DG was increased. Neuronal differentiation was concomitantly reduced however, thus suggesting age-associated changes in fate-choice determination.
    Neurobiology of Aging 08/2014; DOI:10.1016/j.neurobiolaging.2014.07.033 · 4.85 Impact Factor
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    • "Future studies investigating the effects of early running on selective recruitment of these adult-born, mature neurons to learning tasks (using immediate early gene markers) will be useful for our understanding of their functional significance for incorporation into memory circuits. Previous studies using rodents have shown that the effects of running to increase cellular proliferation are evident after only a few days of running (Naylor et al., 2005; Kronenberg et al., 2006; Van Praag, 2008), but that after longer periods of running, this pro-proliferative effect is not evident (Naylor et al., 2005; Kronenberg et al., 2006; Wojtowicz et al., 2008). This may explain why we have not observed any effects of running on proliferation even at short survival times, e.g., 1 week cohort. "
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    ABSTRACT: Adult neurogenesis is highly responsive to environmental and physiological factors. The majority of studies to date have examined short-term consequences of enhancing or blocking neurogenesis but long-term changes remain less well understood. Current evidence for age-related declines in neurogenesis warrant further investigation into these long-term changes. In this report we address the hypothesis that early life experience, such as a period of voluntary running in juvenile rats, can alter properties of adult neurogenesis for the remainder of the animal's life. The results indicate that the number of proliferating and differentiating neuronal precursors is not altered in runners beyond the initial weeks post-running, suggesting homeostatic regulation of these processes. However, the rate of neuronal maturation and survival during a 4 week period after cell division was enhanced up to 11 months of age (the end of the study period). This study is the first to show that a transient period of physical activity at a young age promotes changes in neurogenesis that persist over the long-term, which is important for our understanding of the modulation of neurogenesis by exercise with age. Functional integration of adult-born neurons within the hippocampus that resist homeostatic regulation with aging, rather than the absolute number of adult-born neurons, may be an essential feature of adult neurogenesis that promotes the maintenance of neural plasticity in old age.
    Frontiers in Neuroscience 07/2014; 8:174. DOI:10.3389/fnins.2014.00174 · 3.70 Impact Factor
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