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Unacylated-Ghrelin Impairs Hippocampal Neurogenesis and Memory in Mice and Is Altered in Parkinson’s Dementia in Humans / Amanda Hornsby; Luke Buntwal; Carla Carisi; Vanessa V. Santos; Fionnuala Johnston; Luke Roberts; Martina Sassi; Mathieu Mequinion; Romana Stark; Alex Reichenbach; Sarah H. Lockie; Mario Siervo; Owain Howell; Alwena Morgan; Timothy Wells; Zane B. Andrews; David J. Burn; Jeffrey Davies

Cell Reports Medicine, Volume: 1, Issue: 7, Start page: 100120

Swansea University Authors: Amanda, Hornsby, Luke, Buntwal, Carla, Carisi, Luke, Roberts, Martina, Sassi, Owain, Howell, Alwena, Morgan, Jeffrey, Davies

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Abstract

Blood-borne factors regulate adult hippocampal neurogenesis and cognition in mammals. We report that elevating circulating unacylated-ghrelin (UAG), using both pharmacological and genetic methods, reduced hippocampal neurogenesis and plasticity in mice. Spatial memory impairments observed in ghrelin...

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Published in: Cell Reports Medicine
ISSN: 2666-3791
Published: Elsevier BV 2020
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa55678
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Abstract: Blood-borne factors regulate adult hippocampal neurogenesis and cognition in mammals. We report that elevating circulating unacylated-ghrelin (UAG), using both pharmacological and genetic methods, reduced hippocampal neurogenesis and plasticity in mice. Spatial memory impairments observed in ghrelin-O-acyl transferase-null (GOAT/) mice that lack acyl-ghrelin (AG) but have high levels of UAG were rescued by acyl-ghrelin. Acyl-ghrelin-mediated neurogenesis in vitro was dependent on non-cell-autonomous BDNF signaling that was inhibited by UAG. These findings suggest that post-translational acylation of ghrelin is important to neurogenesis and memory in mice. To determine relevance in humans, we analyzed circulating AG:UAG in Parkinson disease (PD) patients diagnosed with dementia (PDD), cognitively intact PD patients, and controls. Notably, plasma AG:UAG was only reduced in PDD. Hippocampal ghrelin-receptor expression remained unchanged; however, GOAT+ cell number was reduced in PDD. We identify UAG as a regulator of hippocampal-dependent plasticity and spatial memory and AG:UAG as a putative circulating diagnostic biomarker of dementia.
Keywords: ghrelin; GOAT; acyl-ghrelin; unacylated-ghrelin; AG:UAG; adult hippocampal neurogenesis; memory; BDNF; Parkinson disease dementia; biomarker
College: Swansea University Medical School
Issue: 7
Start Page: 100120