title: Short-term calorie restriction enhances adult hippocampal neurogenesis and remote fear memory in a Ghsr-dependent manner.
abstract: The beneficial effects of calorie restriction (CR) have been described at both organismal and cellular levels in multiple organs. However, our understanding of the causal mediators of such hormesis is poorly understood, particularly in the context of higher brain function. Here, we show that the receptor for the orexigenic hormone acyl-ghrelin, the growth hormone secretagogue receptor (Ghsr), is enriched in the neurogenic niche of the hippocampal dentate gyrus (DG). Acute elevation of acyl-ghrelin levels by injection or by overnight CR, increased DG levels of the neurogenic transcription factor, Egr-1. Two weeks of CR increased the subsequent number of mature newborn neurons in the DG of adult wild-type but not Ghsr(-/-) mice. CR wild-type mice also showed improved remote contextual fear memory. Our findings suggest that Ghsr mediates the beneficial effects of CR on enhancing adult hippocampal neurogenesis and memory.
authors.affiliation: Molecular Neurobiology, Institute of Life Sciences, College of Medicine, Swansea University, UK.
authors.forename: Amanda K E
authors.initials: AK
authors.lastname: Hornsby
authors.affiliation: Molecular Neurobiology, Institute of Life Sciences, College of Medicine, Swansea University, UK.
authors.forename: Yushi T
authors.initials: YT
authors.lastname: Redhead
authors.affiliation: Molecular Neurobiology, Institute of Life Sciences, College of Medicine, Swansea University, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rees
authors.affiliation: Molecular Neurobiology, Institute of Life Sciences, College of Medicine, Swansea University, UK.
authors.forename: Michael S G
authors.initials: MS
authors.lastname: Ratcliff
authors.affiliation: Monash University, Victoria, Australia.
authors.forename: Alex
authors.initials: A
authors.lastname: Reichenbach
authors.affiliation: School of Biosciences, Cardiff University, UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Wells
authors.affiliation: Molecular Neurobiology, Institute of Life Sciences, College of Medicine, Swansea University, UK.
authors.forename: Lewis
authors.initials: L
authors.lastname: Francis
authors.affiliation: Texas A&M University, College Station, TX, USA.
authors.forename: Katia
authors.initials: K
authors.lastname: Amstalden
authors.affiliation: Monash University, Victoria, Australia.
authors.forename: Zane B
authors.initials: ZB
authors.lastname: Andrews
authors.affiliation: Molecular Neurobiology, Institute of Life Sciences, College of Medicine, Swansea University, UK. Electronic address: jeff.s.davies@swansea.ac.uk.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Davies
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D031204:Caloric Restriction; D005239:Fear / Q000523:psychology*; D005260:Female; D006624:Hippocampus / Q000166:cytology*; D008297:Male; D011939:Mental Recall / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics*; D054440:Receptors, Ghrelin / Q000235:genetics*; D013997:Time Factors
chemical_list: D054440:Receptors, Ghrelin
keywords: Adult hippocampal neurogenesis; Calorie restriction; Ghrelin; Ghsr