Ghrelin is required for dietary restriction-induced enhancement of hippocampal neurogenesis: lessons from ghrelin knockout mice.
Neurogenesis occurs in the adult hippocampus and is enhanced by dietary restriction (DR), and neurogenesis enhancement is paralleled by circulating ghrelin level enhancement. We have previously reported that ghrelin modulates adult neurogenesis in the hippocampus. In order to investigate the possible role of ghrelin in DR-induced hippocampal neurogenesis in adult mice, ghrelin knockout (GKO) mice and wild-type (WT) mice were maintained for 3 months on DR or ad libitum (AL) diets. Protein levels of ghrelin in the stomach and the hippocampus were increased by DR in WT mice. One day after BrdU administration, the number of BrdU-labeled cells in the hippocampal dentate gyrus was decreased in GKO mice maintained on the AL diet. DR failed to alter the proliferation of progenitor cells in both WT and GKO mice. Four weeks after BrdU injection, the number of surviving cells in the dentate gyrus was decreased in AL-fed GKO mice. DR increased survival of newborn cells in WT mice, but not in GKO mice. Levels of brain-derived neurotrophic factor protein in the hippocampus were similar between WT and GKO mice, and were increased by DR both in WT and GKO mice. These results suggest that elevated levels of ghrelin during DR may have an important role in the enhancement of neurogenesis induced by DR.
Department of Pharmacology and Medical Research Center for Bioreaction to ROS and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Korea.
Yumi
Y
Kim
Sehee
S
Kim
Chanyang
C
Kim
Takahiro
T
Sato
Masayasu
M
Kojima
Seungjoon
S
Park
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D031204:Caloric Restriction; D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D054439:Ghrelin / Q000235:genetics* / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D054439:Ghrelin