Exercise enhances the proliferation of neural stem cells and neurite growth and survival of neuronal progenitor cells in dentate gyrus of middle-aged mice

Abstract

Aging is an important determinant of adult hippocampal neurogenesis as the proliferation of neural stem/precursor cells (NSCs) declines dramatically before middle age. Contrary to this, physical exercise is known to promote adult hippocampal neurogenesis. The objective of this study is to investigate the effects of mandatory treadmill running (TR) on neurogenesis, including 1) NSCs proliferation, 2) neurite outgrowth of neuronal progenitor cells, and 3) the survival of newborn neurons in dentate area of middle-aged animals. Compared with 3-mo-old mice, numbers of mitotic cells and neuronal progenitor cells decreased dramatically by middle age and remained at low levels after middle age. Five weeks of TR not only increased NSC proliferation and the number of immature neurons but also promoted the maturation and survival of immature neurons in middle-aged mice. The neurogenic and neurotrophic effects of TR were not due to the reduction of the age-related elevation of serum corticosterone. Significantly, 5 wk of TR restored the age-dependent decline of brain-derived neurotrophic factor and its receptor, TrkB, which are known to promote neuronal differentiation and survival. Taken together, mandatory running exercise alters the brain chemistries of middle-aged animals toward an environment that is favorable to NSC proliferation, survival, and maturation.

Enhancing Hippocampal Neuronal Numbers in Morphine-Dependent Rats by Voluntary Exercise Through a Brain-Derived Neurotrophic Factor-Mediated Mechanism

“…Blocking BDNF action significantly reduced this effect in both groups, indicating that BDNF mediates the exercise-induced enhancement of neuron numbers. This finding confirms the results of other studies showing the positive effects of exercise on neurogenesis (7,12,22,23). Thus, exercise-induced enhancement in hippocampal BDNF expression and TrkB are necessary for BDNF-mediated effects on neuronal counting in exercising rats.…”

Soft-diet Feeding Inhibits Adult Neurogenesis in Hippocampus of Mice

“…An enhancement of BDNF production has been shown to enhance neural precursor cell proliferation in the subgranular zone 10) , and a shortage of BDNF content has been linked to a drop in neurogenesis 18) . The action of BDNF is mediated by the specific tyrosine kinase receptor TrkB, which is also widely expressed in the dentate gyrus 23) . Age-dependent decline in adult hippocampal neurogenesis is a consequence of chronically elevated circulating levels of corticosteroids 1) , whose levels are elevated in aged animals 2) .…”

Combined Exercise and Insulin-Like Growth Factor-1 Supplementation Induces Neurogenesis in Old Rats, but Do Not Attenuate Age-Associated DNA Damage

“…However, a recent report has challenged this finding, because the data from this study showed that exercise was able to improve results on the Morris water maze test, even with inhibition of neurogenesis. 64 Most studies on neurogenesis have used voluntary running, 65,66 but studies using enforced running 37,67 have shown similar results. However, the data from these studies further suggest that voluntary and treadmill running have different effects on brain plasticity in different regions of the brain.…”