Aging and Exercise Affect Hippocampal Neurogenesis via Different Mechanisms

PLoS One. 2015 Jul 6;10(7):e0132152. doi: 10.1371/journal.pone.0132152. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • Male
  • Mice
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neurogenesis / physiology*
  • Neurons / cytology
  • Neurons / metabolism*
  • Physical Conditioning, Animal / physiology*

Grants and funding

This work was supported by Ministry of Science and Technology 102-2314-B-214-006-MY3 (TTY) and 101-2320-B-006-006-MY3 (YMK) of Taiwan, Republic of China. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.