Melatonin supplementation delays the decline of adult hippocampal neurogenesis during normal aging of mice

Neurosci Lett. 2012 Nov 14;530(1):53-8. doi: 10.1016/j.neulet.2012.09.045. Epub 2012 Oct 6.


Melatonin modulates adult hippocampal neurogenesis in adult mice. Also, plasma melatonin levels and new neuron formation decline during aging probably causing cognitive alterations. In this study, we analyzed the impact of exogenous supplementation with melatonin in three key events of hippocampal neurogenesis during normal aging of mice. The analysis was performed in rodents treated with melatonin during 3, 6, 9 or 12 months. We found an increase in cell proliferation in the dentate gyrus of the hippocampus after 3, 6 and 9 months of treatment (>90%). Additionally, exogenous melatonin promoted survival of new cells in the dentate gyrus (>50%). Moreover, melatonin increased the number of doublecortin-labeled cells after 6 and 9 months of treatment (>150%). In contrast, melatonin administered during 12 months did not induce changes in hippocampal neurogenesis. Our results indicate that melatonin also modulates the neurogenic process in the hippocampus during normal aging of mice. Together, the data support melatonin as one of the positive endogenous regulators of neurogenesis during aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Central Nervous System Depressants / pharmacology
  • Cognition / physiology
  • Dentate Gyrus / cytology*
  • Dentate Gyrus / drug effects*
  • Dentate Gyrus / physiology
  • Doublecortin Domain Proteins
  • Male
  • Melatonin / pharmacology*
  • Melatonin / physiology
  • Mice
  • Mice, Inbred BALB C
  • Microtubule-Associated Proteins / metabolism
  • Neurogenesis / drug effects*
  • Neurogenesis / physiology
  • Neurons / cytology
  • Neurons / metabolism
  • Neuropeptides / metabolism


  • Central Nervous System Depressants
  • Doublecortin Domain Proteins
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Melatonin