title: Ghrelin administration enhances neurogenesis but impairs spatial learning and memory in adult mice.
abstract: Ghrelin, an orexigenic brain-gut hormone promoting feeding and regulating energy metabolism in human and rodents, was reported to enhance both adult neurogenesis and hippocampus-dependent memory formation. However, it is still unclear whether ghrelin-induced hippocampus neurogenesis is responsible for its memory improvement. Using 5-bromo-2' deoxyuridien (BrdU) to birth-date newborn neurons and c-Fos expression to identify dentate gyrus (DG) neurons involved in memory processes, we checked here the effect of ghrelin treatment on adult neurogenesis and cognitive behaviors in mice. We further examined the possible effect of ghrelin on the recruitment of new neurons into the spatial memory traces in intact mice. We found that systemic ghrelin treatment (80μg/kg, ip injection once daily for 8days) stimulated neurogenesis in the adult hippocampus, but had no effect on spatial memory formation. Consistently, it did not affect the incorporation of newborn neurons into the spatial memory circuits. On the contrary, local infusion of ghrelin (8ng/0.5μl into CA1 region of the hippocampus) impaired spatial memory formation, but did not affect adult neurogenesis. Our results thus suggested that ghrelin plays distinct roles in modulating adult neurogenesis and the memory acquisition in the hippocampus, the two processes may not be correlated and may be mediated by different mechanisms.
authors.affiliation: Department of Physiology, Medical College of Qingdao University, Qingdao, Shandong 266071, China; Department of Neurology, Medical College Affiliated General Hospital, Qingdao, Shandong 266021, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Physiology, Medical College of Qingdao University, Qingdao, Shandong 266071, China; Department of Physiology, Binzhou Medical College, Yantai, Shandong 266021, China.
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Physiology, Medical College of Qingdao University, Qingdao, Shandong 266071, China.
authors.forename: K
authors.initials: K
authors.lastname: Xiao
authors.affiliation: Department of Physiology, Medical College of Qingdao University, Qingdao, Shandong 266071, China.
authors.forename: M
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Physiology, Medical College of Qingdao University, Qingdao, Shandong 266071, China.
authors.forename: L
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Physiology, Medical College of Qingdao University, Qingdao, Shandong 266071, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Medical College Affiliated General Hospital, Qingdao, Shandong 266021, China.
authors.forename: R
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. Electronic address: guodongli@mednet.ucla.edu.
authors.forename: G-D
authors.initials: GD
authors.lastname: Li
authors.affiliation: Department of Physiology, Medical College of Qingdao University, Qingdao, Shandong 266071, China. Electronic address: yuzhou7310@gmail.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine; D002452:Cell Count; D000089622:Doublecortin Domain Proteins; D005106:Exploratory Behavior / Q000187:drug effects; D054439:Ghrelin / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007858:Learning / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced*; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D013997:Time Factors
chemical_list: D000089622:Doublecortin Domain Proteins; D054439:Ghrelin; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D016761:Oncogene Proteins v-fos; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine
keywords: 5-bromo-2′ deoxyuridien; BrdU; DG; PFA; SGZ; TQ; adult neurogenesis; dentate gyrus; ghrelin; hippocampus; learning; memory circuits; paraformaldehyde; subgranular zone; target quadrant