Melatonin improves D-galactose-induced aging effects on behavior, neurogenesis, and lipid peroxidation in the mouse dentate gyrus via increasing pCREB expression

J Pineal Res. 2012 Jan;52(1):21-8. doi: 10.1111/j.1600-079X.2011.00912.x. Epub 2011 Jul 1.

Abstract

Melatonin (N-acetyl-5-methoxytryptamine) has multiple functions. In this study, we investigated the effects of melatonin on memory, cell proliferation, and neuroblast differentiation in the dentate gyrus of a mouse model of D-galactose-induced aging. D-galactose was subcutaneously administered to 7-wk-old mice for 10 wk, and age-matched mice were used as controls. Seven weeks after D-galactose administration, vehicle (water) or melatonin (6 mg/L in water) was administered ad libitum to the mice for 3 wk. The administration of D-galactose significantly increased the escape latency compared with that in the control mice on days 1-3. In addition, cells in the subgranular zone and in the granule cell layer of the dentate gyrus showed severe damage (cytoplasmic condensation) in the D-galactose-treated mice. However, melatonin supplementation to these mice for 3 wk significantly ameliorated the D-galactose-induced increase in escape latency and neuronal damage compared with the vehicle-treated group. The administration of melatonin also significantly restored the D-galactose-induced reduction of proliferating cells (Ki67-positive cells) and differentiating neuroblasts (doublecortin-positive neuroblasts) in the dentate gyrus. Furthermore, the administration of melatonin significantly increased Ser133-phosphorylated cyclic AMP response element binding protein in the dentate gyrus. The administration of melatonin significantly reduced D-galactose-induced lipid peroxidation in the dentate gyrus. These results suggest that melatonin may be helpful in reducing age-related phenomena in the brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cellular Senescence / drug effects
  • Cyclic AMP / metabolism
  • Dentate Gyrus / chemistry
  • Dentate Gyrus / cytology
  • Dentate Gyrus / drug effects*
  • Dentate Gyrus / metabolism
  • Doublecortin Domain Proteins
  • Galactose / pharmacology*
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Lipid Peroxidation / drug effects
  • Male
  • Maze Learning / drug effects
  • Melatonin / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / metabolism
  • Neurogenesis / drug effects*
  • Neuropeptides / metabolism

Substances

  • Doublecortin Domain Proteins
  • Ki-67 Antigen
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Cyclic AMP
  • Melatonin
  • Galactose