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Unacylated-Ghrelin Impairs Hippocampal Neurogenesis and Memory in Mice and Is Altered in Parkinson’s Dementia in Humans
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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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DOI (Published version): 10.1016/j.xcrm.2020.100120
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...
| Published in: | Cell Reports Medicine |
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| ISSN: | 2666-3791 |
| Published: |
Elsevier BV
2020
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| Online Access: |
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| 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. |
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| Keywords: |
ghrelin; GOAT; acyl-ghrelin; unacylated-ghrelin; AG:UAG; adult hippocampal neurogenesis; memory; BDNF; Parkinson disease dementia; biomarker |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Issue: |
7 |
| Start Page: |
100120 |