Moderate-Intensity Exercise Induces Neurogenesis and Improves Cognition in Old Mice by Upregulating Hippocampal Hippocalcin, Otub1, and Spectrin-α

  • Ji Hyun Kim
  • Quan Feng Liu
  • Enerelt Urnuhsaikhan
  • Ha Jin Jeong
  • Mi Yang JeonEmail author
  • Songhee JeonEmail author


Exercise increases the levels of neurogenic factors and enhances neurogenesis, memory, and learning. However, the molecular link between exercise and neurogenesis is not clear. The purpose of this study was to examine the effects of exercise intensity on cognitive function and protein expression in the hippocampus of old mice. To compare the effects of aerobic exercise intensity on cognition in old mice, we exposed 18-month-old mice to low- and moderate-intensity treadmill exercise for 4 weeks. Moderate-intensity exercise improved cognitive function in the old mice, while low-intensity exercise did not. To investigate the underlying mechanisms, two-dimensional electrophoresis was used to examine protein expression. Using peptide fingerprinting mass spectrometry, we identified 19 proteins that were upregulated in the hippocampus following exercise training, and seven of these proteins were normalized by the control value. Among them, the levels of 14-3-3 zeta and heat shock protein 70, which have been shown to be induced by exercise training and related to neurogenesis, were dramatically increased by moderate exercise. Hippocalcin, α-spectrin, ovarian tumor domain-containing ubiquitin aldehyde-binding protein 1 (otub1), mu-crystallin, serine racemase, and rho GDP dissociation inhibitor 1, which are related to neurogenesis, neuroprotection, and synaptic strength, were upregulated in the hippocampus by moderate exercise. In addition, we confirmed that neurogenic markers, including doublecortin and the neuronal nuclei antigen, and hippocalcin, otub1, and spectrin-α are potential molecular links between hippocampal neurogenesis and exercise in the elderly. Thus, these results showed that steady moderate-intensity exercise delayed the declines in cognitive function in the elderly through the activation of multiple factors.


Aerobic exercise Old mouse Neurogenesis Cognitive function Hippocalcin Otub1 Spectrin-α Mu-crystallin 


Funding Information

This work was supported by the Institute of Health Science, Gyeongsang National University, 2015.

Compliance with Ethical Standards

The animal use protocols were reviewed and approved by the Institutional Animal Care and Use Committee of Dongguk University Ilsan Hospital (No. 201603147) and were in accordance with the National Institutes of Health guidelines.

Conflict of Interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NursingJinju Health CollegeJinjuRepublic of Korea
  2. 2.Department of Neuropsychiatry, Graduate School of Oriental MedicineDongguk UniversityGyeongjuRepublic of Korea
  3. 3.Department of Biology, School of Art and SciencesNational University of MongoliaUlaanbaatarMongolia
  4. 4.Department of Biomedical SciencesCenter for Creative Biomedical Scientists at Chonnam National UniversityGwangjuRepublic of Korea
  5. 5.College of Nursing, Institute of Health ScienceGyengsang National UniversityJinjuRepublic of Korea

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