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Unacylated-Ghrelin Impairs Hippocampal Neurogenesis and Memory in Mice and Is Altered in Parkinson's Dementia in Humans.
- Source :
-
Cell reports. Medicine [Cell Rep Med] 2020 Oct 20; Vol. 1 (7), pp. 100120. Date of Electronic Publication: 2020 Oct 20. - Publication Year :
- 2020
-
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 <superscript>-/-</superscript> ) 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 <superscript>+</superscript> 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.<br />Competing Interests: The authors declare no competing interests.<br /> (© 2020 The Author(s).)
- Subjects :
- Acyltransferases deficiency
Animals
Brain-Derived Neurotrophic Factor genetics
Brain-Derived Neurotrophic Factor metabolism
Cognition physiology
Disease Models, Animal
Female
Gene Expression Regulation
Ghrelin metabolism
Hippocampus pathology
Humans
Male
Membrane Proteins deficiency
Mice
Mice, Inbred C57BL
Mice, Knockout
Neurogenesis genetics
Neuronal Plasticity genetics
Neurons metabolism
Neurons pathology
Parkinson Disease metabolism
Parkinson Disease pathology
Primary Cell Culture
Rats
Signal Transduction
Spatial Memory physiology
Supranuclear Palsy, Progressive metabolism
Supranuclear Palsy, Progressive pathology
Acyltransferases genetics
Ghrelin analogs & derivatives
Ghrelin genetics
Hippocampus metabolism
Membrane Proteins genetics
Parkinson Disease genetics
Supranuclear Palsy, Progressive genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2666-3791
- Volume :
- 1
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cell reports. Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 33103129
- Full Text :
- https://doi.org/10.1016/j.xcrm.2020.100120