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: 5.01). 11/2006; 27(10):1505-13. DOI: 10.1016/j.neurobiolaging.2005.09.016
Source: PubMed


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 any case, adult neurogenesis occurs at only a very low rate during most of the life, so that any growth would only become noticeable relatively early in life. Adult hippocampal neurogenesis decreases rather sharply in young adulthood and is maintained at a low level throughout most of the remaining life (Kronenberg et al., 2005). In 20-month-old mice we found that only 11 cells were generated over a period of 12 days (Kempermann et al., 2002). "
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    ABSTRACT: Organisms need to adapt to the ecological constraints in their habitat. How specific processes reflect such adaptations are difficult to model experimentally. We tested whether environmental shifts in oxygen tension lead to events in the adult newt brain that share features with processes occuring during neuronal regeneration under normoxia. By experimental simulation of varying oxygen concentrations we show that hypoxia followed by re-oxygenation lead to neuronal death and hallmarks of an injury response, including activation of neural stem cells ultimately leading to neurogenesis. Neural stem cells accumulate reactive oxygen species (ROS) during re-oxygenation and inhibition of ROS biosynthesis counteracts their proliferation as well as neurogenesis. Importantly, regeneration of dopamine neurons under normoxia also depends on ROS-production. These data demonstrate a role for ROS-production in neurogenesis in newts, and suggest that this role may have been recruited to the capacity to replace lost neurons in the brain of an adult vertebrate.
    eLife Sciences 10/2015; 4. DOI:10.7554/eLife.08422 · 9.32 Impact Factor
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    • "Several of these regulated genes are known to play a role in adult hippocampal neurogenesis. Adult neurogenesis in the subgranular zone of the DG is remarkably decreased in aged animals (Kuhn et al., 1996; Bondolfi et al., 2004) and this decrease can be partially reversed following exercise (van Praag et al., 2005; Kronenberg et al., 2006). However, though adult neurogenesis has been shown to be a necessary mechanism for the improvement of fine-scale spatial and contextual discrimination in adult mice (Clelland et al., 2009; Creer et al., 2010; Sahay et al., 2011a; Tronel et al., 2012), it may not fully account for the positive cognitive effects of exercise in young adult and aged animals (Meshi et al., 2006; Creer et al., 2010; Madroñal et al., 2010). "
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    ABSTRACT: Normal aging and exercise exert extensive, often opposing, effects on the dentate gyrus (DG) of the hippocampus altering volume, synaptic function, and behaviors. The DG is especially important for behaviors requiring pattern separation-a cognitive process that enables animals to differentiate between highly similar contextual experiences. To determine how age and exercise modulate pattern separation in an aversive setting, young, aged, and aged mice provided with a running wheel were assayed on a fear-based contextual discrimination task. Aged mice showed a profound impairment in contextual discrimination compared to young animals. Voluntary exercise rescued this deficit to such an extent that behavioral pattern separation of aged-run mice was now similar to young animals. Running also resulted in a significant increase in the number of immature neurons with tertiary dendrites in aged mice. Despite this, neurogenesis levels in aged-run mice were still considerably lower than in young animals. Thus, mechanisms other than DG neurogenesis likely play significant roles in improving behavioral pattern separation elicited by exercise in aged animals.
    Frontiers in Systems Neuroscience 08/2015; 9:114. DOI:10.3389/fnsys.2015.00114
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    • "According to Van Praag et al., the voluntary physical exercises of young adult (3-month-old) mice promoted cell proliferation, cell survival, and neurogenesis within the DG [138]. Other studies also demonstrated the exercise-mediated increases in neurogenesis in the DGs of the hippocampus in young, adult, and aged animals [139] [140] [141] [142] [143] [144]. Moreover, running has been shown to improve the cognitive functions in aged mice and humans [145] [146] [147]. "
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    ABSTRACT: Diabetes mellitus is one of the most common serious metabolic diseases that results in hyperglycemia due to defects of insulin secretion or insulin action or both. The present review focuses on the alterations to the diabetic neuronal tissues and skeletal muscle, including stem cells in both tissues, and the preventive effects of physical activity on diabetes. Diabetes is associated with various nervous disorders, such as cognitive deficits, depression, and Alzheimer’s disease, and that may be caused by neural stem cell dysfunction. Additionally, diabetes induces skeletal muscle atrophy, the impairment of energy metabolism, and muscle weakness. Similar to neural stem cells, the proliferation and differentiation are attenuated in skeletal muscle stem cells, termed satellite cells. However, physical activity is very useful for preventing the diabetic alteration to the neuronal tissues and skeletal muscle. Physical activity improves neurogenic capacity of neural stem cells and the proliferative and differentiative abilities of satellite cells. The present review proposes physical activity as a useful measure for the patients in diabetes to improve the physiological functions and to maintain their quality of life. It further discusses the use of stem cell-based approaches in the context of diabetes treatment.
    05/2015; 2015:1-16. DOI:10.1155/2015/592915
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