title: Acyl ghrelin improves cognition, synaptic plasticity deficits and neuroinflammation following amyloid β (Aβ1-40) administration in mice.
abstract: Ghrelin is a metabolic hormone that has neuroprotective actions in a number of neurological conditions, including Parkinson's disease (PD), stroke and traumatic brain injury. Acyl ghrelin treatment in vivo and in vitro also shows protective capacity in Alzheimer's disease (AD). In the present study, we used ghrelin knockout (KO) and their wild-type littermates to test whether or not endogenous ghrelin is protective in a mouse model of AD, in which human amyloid β peptide 1-40 (Aβ1-40) was injected into the lateral ventricles i.c.v. Recognition memory, using the novel object recognition task, was significantly impaired in ghrelin KO mice and after i.c.v. Aβ1-40treatment. These deficits could be prevented by acyl ghrelin injections for 7 days. Spatial orientation, as assessed by the Y-maze task, was also significantly impaired in ghrelin KO mice and after i.c.v. Aβ1-40treatment. These deficits could be prevented by acyl ghrelin injections for 7 days. Ghrelin KO mice had deficits in olfactory discrimination; however, neither i.c.v. Aβ1-40treatment, nor acyl ghrelin injections affected olfactory discrimination. We used stereology to show that ghrelin KO and Aβ1-40increased the total number of glial fibrillary acidic protein expressing astrocytes and ionised calcium-binding adapter expressing microglial in the rostral hippocampus. Finally, Aβ1-40blocked long-term potentiation induced by high-frequency stimulation and this effect could be acutely blocked with co-administration of acyl ghrelin. Collectively, our studies demonstrate that ghrelin deletion affects memory performance and also that acyl ghrelin treatment may delay the onset of early events of AD. This supports the idea that acyl ghrelin treatment may be therapeutically beneficial with respect to restricting disease progression in AD.
authors.affiliation: Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, VIC, Australia.
authors.forename: V V
authors.initials: VV
authors.lastname: Santos
authors.affiliation: Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, VIC, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Stark
authors.affiliation: Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina UFSC, Florianópolis, SC, Brazil.|CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Rial
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: H B
authors.initials: HB
authors.lastname: Silva
authors.affiliation: Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, VIC, Australia.
authors.forename: J A
authors.initials: JA
authors.lastname: Bayliss
authors.affiliation: Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, VIC, Australia.
authors.forename: M B
authors.initials: MB
authors.lastname: Lemus
authors.affiliation: Molecular Neurobiology, Institute of Life Science, Swansea University, Swansea, UK.
authors.forename: J S
authors.identifier: 0000-0002-4234-0033
authors.initials: JS
authors.lastname: Davies
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.|Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: R A
authors.initials: RA
authors.lastname: Cunha
authors.affiliation: Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina UFSC, Florianópolis, SC, Brazil.
authors.forename: R D
authors.initials: RD
authors.lastname: Prediger
authors.affiliation: Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, VIC, Australia.
authors.forename: Z B
authors.identifier: 0000-0002-9097-7944
authors.initials: ZB
authors.lastname: Andrews
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D054439:Ghrelin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000187:drug effects*; D000072458:Orientation, Spatial / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D054439:Ghrelin; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)
keywords: Acyl ghrelin; Alzheimer's disease; Y-maze; amyloid β; ghrelin knockout; novel object recognition; olfactory discrimination