title: Ghrelin stimulates proliferation, migration and differentiation of neural progenitors from the subventricular zone in the adult mice.
abstract: Ghrelin has been shown to regulate neurogenesis in the hippocampus. The aim of this study was to investigate the possible influence of ghrelin on cell proliferation and neuroblast formation in the subventricular zone (SVZ) and rostral migratory system (RMS) and generation of interneurons in the olfactory bulb (OB). We found that ghrelin receptors were expressed in the SVZ-RMS-OB system. Ghrelin knockout (GKO) mice have fewer proliferating neural progenitor cells and neuroblasts in the SVZ, while ghrelin administration attenuated these changes. We also found that not only the number of BrdU-labeled cells but also the fraction of migratory neuroblasts in the RMS was decreased in the GKO mice compared with controls. Treatment of GKO mice with ghrelin restored these numbers to the wild-type control values. Far fewer BrdU/NeuN double-labeled cells were found in the OB of GKO mice than in wild-type mice 4 weeks after labeling, which were increased by ghrelin replacement. GKO mice showed less numbers of BrdU/calbindin, BrdU/calretinin and BrdU/tyrosine hydroxylase double-labeled cells in the periglomerular layer of the OB. However, these numbers were increased to wild-type values after ghrelin administration. Finally, in the GH-deficient spontaneous dwarf rats, ghrelin increased the number of progenitor cells and neuroblasts in the SVZ, without significant effect on the differentiation in the OB. These findings suggest that ghrelin is involved in the regulation of proliferation of progenitor cells in the SVZ, the number of migratory neuroblasts in the SVZ, and the differentiation of interneurons in the OB.
authors.affiliation: Department of Pharmacology and Medical Research Center for Bioreaction to ROS and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Endan
authors.initials: E
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Medical Research Center for Bioreaction to ROS and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Pharmacology and Medical Research Center for Bioreaction to ROS and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Sehee
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Molecular Genetics, Institute of Life Science, Kurume University, Hyakunen-kohen 1-1, Kurume, Fukuoka, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Molecular Genetics, Institute of Life Science, Kurume University, Hyakunen-kohen 1-1, Kurume, Fukuoka, Japan.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Kojima
authors.affiliation: Department of Pharmacology and Medical Research Center for Bioreaction to ROS and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea. Electronic address: sjpark@khu.ac.kr.
authors.forename: Seungjoon
authors.initials: S
authors.lastname: Park
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D064032:Calbindin 2 / Q000378:metabolism; D064026:Calbindins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D054439:Ghrelin / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology*; D019394:Ki-67 Antigen / Q000378:metabolism; D020547:Lateral Ventricles / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D009830:Olfactory Bulb / Q000166:cytology; D054440:Receptors, Ghrelin / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D064032:Calbindin 2; D064026:Calbindins; D054439:Ghrelin; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; D054440:Receptors, Ghrelin; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; D014446:Tyrosine 3-Monooxygenase; D001973:Bromodeoxyuridine
keywords: Adult neurogenesis; Ghrelin; Olfactory bulb; Rostral migratory system; Subventricular zone