title: An examination of early neural and cognitive alterations in hippocampal-spatial function of ghrelin receptor-deficient rats.
abstract: Ghrelin, a hormone implicated in the regulation of feeding and energy balance, has also been associated with neural function underlying learning and memory. These effects are thought to be mediated by ghrelin targeting receptors at extra hypothalamic sites such as the hippocampus. Exogenous ghrelin administration increases dendritic spine density in the hippocampal CA1 region and neurogenesis in the dentate gyrus (DG), while improving memory in rats. In the present study, we sought to determine whether rats lacking the ghrelin receptor would show early neural or cognitive decline measured via hippocampal integrity (spine density and neurogenesis) and spatial learning and memory. As such, we used young and middle-aged adult rats with mutations to the gene encoding for the ghrelin receptor (GHS-R KO) and wildtype (WT) littermates to determine differences in performance on hippocampal-dependent tasks (the water maze and radial arm maze). In addition, we examined the hippocampal dentate gyrus of these rats for differences in dendritic spine density and cell proliferation (doublecortin). Overall, results demonstrated that spine density and doublecortin staining in the dentate gyrus of the young GHS-R KO group was similar to that seen in middle-aged groups (both KO and WT) and lower than the young WT group. Middle-aged GHS-R KO and WT groups showed deficits on the radial arm maze food-motivated task but not the water maze task. These data suggest that impaired ghrelin signaling leads to an early onset decrement in hippocampal structural integrity that may manifest in non- spatial-related behavioral deficits.
authors: Department of Neuroscience, Carleton University, Ottawa, ON, Canada.
authors: Shaina P
authors: SP
authors: Cahill
authors: Department of Neuroscience, Carleton University, Ottawa, ON, Canada.
authors: Taylor
authors: T
authors: Hatchard
authors: Department of Neuroscience, Carleton University, Ottawa, ON, Canada.
authors: Alfonso
authors: A
authors: Abizaid
authors: Department of Neuroscience, Carleton University, Ottawa, ON, Canada. Electronic address: matthew_holahan@carleton.ca.
authors: Matthew R
authors: MR
authors: Holahan
mesh_terms: D000367:Age Factors; D000818:Animals; D001835:Body Weight / Q000235:genetics; D003072:Cognition Disorders / Q000097:blood / Q000235:genetics* / Q000473:pathology; D049229:Dendritic Spines / Q000473:pathology; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005106:Exploratory Behavior; D005786:Gene Expression Regulation / Q000235:genetics*; D054439:Ghrelin / Q000097:blood; D006624:Hippocampus / Q000473:pathology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D054440:Receptors, Ghrelin / Q000172:deficiency* / Q000235:genetics; D016622:Silver Staining; D013028:Space Perception / Q000502:physiology*; D013997:Time Factors
chemical_list: C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D054439:Ghrelin; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D054440:Receptors, Ghrelin
keywords: Ghrelin; Neurogenesis; Radial arm maze; Spatial memory; Spines; Water maze