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.
Highlights
Neural stem/precursor cells (NSCs) in the subventricular zone and subgranular zone of dentate gyrus in hippocampus produce new cells throughout adulthood [1,2]
Aging and Exercise Affect Adult Hippocampal Neurogenesis revealed that the formation, exhibition and/or clearance of certain types of hippocampusdependent memory are influenced by adult hippocampal neurogenesis [7,8]
By the time the mice reached 9 months of age, the number of BrdU+DCX+ cells was only 1.5% of the cell number in the 3-month-old mice (Fig 1I). These results showed that the decline of adult hippocampal neurogenesis mainly occurred before middle age
Summary
Neural stem/precursor cells (NSCs) in the subventricular zone and subgranular zone of dentate gyrus in hippocampus produce new cells throughout adulthood [1,2]. The rate of adult hippocampal neurogenesis is controlled by the following four determinants: 1) the number of NSCs in the dentate gyrus, 2) proliferation rate of the NSCs, 3) neuronal lineage specification rate of newly proliferated cells, and 4) survival rate of newborn neurons. It is unclear whether aging and Ex act on the same determinant(s) to affect the rate of adult hippocampal neurogenesis or these two factors differentially influence their own targets
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