No Cover Image

Journal article 124 views 16 downloads

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

  • Hornsby et al.2020.pdf

    PDF | Version of Record

    ©2020 The Author(s). This is an open access article under the CC BY license

    Download (7.74MB)

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...

Full description

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
Tags: Add Tag
No Tags, Be the first to tag this record!
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