Aging and Exercise Affect Hippocampal Neurogenesis via Different Mechanisms

Abstract

The rate of neurogenesis is determined by 1) the number of neural stem/progenitor cells (NSCs), 2) proliferation of NSCs, 3) neuron lineage specification, and 4) survival rate of the newborn neurons. Aging lowers the rate of hippocampal neurogenesis, while exercise (Ex) increases this rate. However, it remains unclear which of the determinants are affected by aging and Ex. We characterized the four determinants in different age groups (3, 6, 9, 12, 21 months) of mice that either received one month of Ex training or remained sedentary. Bromodeoxyuridine (BrdU) was injected two hours before sacrificing the mice to label the proliferating cells. The results showed that the number of newborn neurons massively decreased (>95%) by the time the mice reached nine months of age. The number of NSC was mildly reduced during aging, while Ex delayed such decline. The proliferation rates were greatly decreased by the time the mice were 9-month-old and Ex could not improve the rates. The rates of neuron specification were decreased during aging, while Ex increased the rates. The survival rate was not affected by age or Ex. Aging greatly reduced newborn neuron maturation, while Ex potently enhanced it. In conclusion, age-associated decline of hippocampal neurogenesis is mainly caused by reduction of NSC proliferation. Although Ex increases the NSC number and neuron specification rates, it doesn't restore the massive decline of NSC proliferation rate. Hence, the effect of Ex on the rate of hippocampal neurogenesis during aging is limited, but Ex does enhance the maturation of newborn neurons.

Skeletal myofiber vascular endothelial growth factor is required for the exercise training‐induced increase in dentate gyrus neuronal precursor cells

“…In this study we found, as reported by several other laboratories (van Praag et al 1999;Fabel et al 2003;Yang et al 2015), that voluntary wheel running for two weeks increases the number of neuronal precursor cells in the dentate gyrus of the hippocampus. The new findings in the present study are as follows.…”

“…; Yang et al . ), that voluntary wheel running for two weeks increases the number of neuronal precursor cells in the dentate gyrus of the hippocampus. The new findings in the present study are as follows.…”

“…Improvements in brain function stem from an ability to increase or maintain the number of new neurons in hippocampal regions (van Praag et al 1999). This seems to be particularly important during ageing, and exercise has been shown to slow the loss of neuronal stem cells and promote their commitment to a neuronal-specific lineage (Yang et al 2015). New neurons within the dentate gyrus of the hippocampus reside in a highly vascularized environment in contact with endothelial cells (Shen et al 2004).…”

Long-Term Moderate Exercise Rescues Age-Related Decline in Hippocampal Neuronal Complexity and Memory

“…Exercise training increases hippocampus size, improves memory, and reduces the risk for Alzheimer’s disease [19]. In animal models, running exercise improves memory performance [20], increases adult hippocampal neurogenesis [21], counteracts the effect of depression [22], and facilitates functional recovery after a brain injury [23] and in neurodegenerative disease [24]. Moreover, regular exercise enriches the dendritic complexity and spine density of the hippocampal CA1 neurons and upregulates some of the synaptic proteins in young mice and rats [20].…”

Movement impairment: Focus on the brain

“…Neuron specification is reduced during aging, and exercise increases this specification. The survival rate is not affected by age or exercise, but aging greatly reduces newborn neuron maturation, and exercise exerts an opposite effect (Yang et al, ). These results strongly indicate that exercise increases both the NSC number and the neuron specification rate.…”