Unacylated-Ghrelin Impairs Hippocampal Neurogenesis and Memory in Mice and Is Altered in Parkinson's Dementia in Humans.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33103129.
- Also identified by DOI 10.1016/j.xcrm.2020.100120 and PMC identifier 7575905.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-/-</sup>) mice that lack acyl-ghrelin (AG) but have high levels of UAG were rescued by acyl-ghrelin. Acyl-ghrelin-mediated neurogenesis <i>in vitro</i> was dependent on non-cell-autonomous BDNF signaling that was inhibited by UAG. These findings suggest that post-translational <i>acylation</i> 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<sup>+</sup> 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.
Medical subject headings
- Acyltransferases
- Ghrelin
- Hippocampus
- Membrane Proteins
- Parkinson Disease
- Supranuclear Palsy, Progressive