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Ghrelin Bridges DMV Neuropathology and GI Dysfunction in the Early Stages of Parkinson's Disease

Ghrelin contributes to the communication between the brain and gastrointestinal (GI) tract. Both decreased ghrelin levels and functional GI disorders are early events in Parkinson's disease (PD) patients and animal models. However, the reason is not clear. Here it is found that choline acetyltr...

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Autores principales: Liu, Yizhen, Wang, Weiwei, Song, Ning, Jiao, Lingling, Jia, Fengju, Du, Xixun, Chen, Xi, Yan, Chunling, Jiao, Jianwei, Jiao, Qian, Jiang, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9596842/
https://www.ncbi.nlm.nih.gov/pubmed/36050877
http://dx.doi.org/10.1002/advs.202203020
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author Liu, Yizhen
Wang, Weiwei
Song, Ning
Jiao, Lingling
Jia, Fengju
Du, Xixun
Chen, Xi
Yan, Chunling
Jiao, Jianwei
Jiao, Qian
Jiang, Hong
author_facet Liu, Yizhen
Wang, Weiwei
Song, Ning
Jiao, Lingling
Jia, Fengju
Du, Xixun
Chen, Xi
Yan, Chunling
Jiao, Jianwei
Jiao, Qian
Jiang, Hong
author_sort Liu, Yizhen
collection PubMed
description Ghrelin contributes to the communication between the brain and gastrointestinal (GI) tract. Both decreased ghrelin levels and functional GI disorders are early events in Parkinson's disease (PD) patients and animal models. However, the reason is not clear. Here it is found that choline acetyltransferase (ChAT)‐positive neurons in the dorsal motor nucleus of the vagus nerve (DMV), are lost in PD transgenic mice. In response to the selective damaging of DMV neurons with mu p75‐SAP, a rapid reduction both in plasma total and active ghrelin levels is observed. While by contrast, chemogenetic activation of DMV cholinergic neurons can increase the plasma ghrelin levels. Impairment of cholinergic neurons is accompanied by GI disorders, including decreased stool wet weight, stool dry weight, small intestine advancing rate, and gastric emptying rate, while exogenous ghrelin treatment can partially ameliorate GI dysfunction of A53T α‐synuclein transgenic mice. Using pseudorabies virus retrograde trace method, the existence of a direct pathway from the stomach fundus to the DMV is shown. Taken together, the findings suggest that the reduction in plasma ghrelin levels in the early stages of PD may be the result of the lesion of cholinergic neurons in the DMV, thus linking neurodegeneration and GI dysfunction in PD.
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spelling pubmed-95968422022-10-27 Ghrelin Bridges DMV Neuropathology and GI Dysfunction in the Early Stages of Parkinson's Disease Liu, Yizhen Wang, Weiwei Song, Ning Jiao, Lingling Jia, Fengju Du, Xixun Chen, Xi Yan, Chunling Jiao, Jianwei Jiao, Qian Jiang, Hong Adv Sci (Weinh) Research Articles Ghrelin contributes to the communication between the brain and gastrointestinal (GI) tract. Both decreased ghrelin levels and functional GI disorders are early events in Parkinson's disease (PD) patients and animal models. However, the reason is not clear. Here it is found that choline acetyltransferase (ChAT)‐positive neurons in the dorsal motor nucleus of the vagus nerve (DMV), are lost in PD transgenic mice. In response to the selective damaging of DMV neurons with mu p75‐SAP, a rapid reduction both in plasma total and active ghrelin levels is observed. While by contrast, chemogenetic activation of DMV cholinergic neurons can increase the plasma ghrelin levels. Impairment of cholinergic neurons is accompanied by GI disorders, including decreased stool wet weight, stool dry weight, small intestine advancing rate, and gastric emptying rate, while exogenous ghrelin treatment can partially ameliorate GI dysfunction of A53T α‐synuclein transgenic mice. Using pseudorabies virus retrograde trace method, the existence of a direct pathway from the stomach fundus to the DMV is shown. Taken together, the findings suggest that the reduction in plasma ghrelin levels in the early stages of PD may be the result of the lesion of cholinergic neurons in the DMV, thus linking neurodegeneration and GI dysfunction in PD. John Wiley and Sons Inc. 2022-09-01 /pmc/articles/PMC9596842/ /pubmed/36050877 http://dx.doi.org/10.1002/advs.202203020 Text en © 2022 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Liu, Yizhen
Wang, Weiwei
Song, Ning
Jiao, Lingling
Jia, Fengju
Du, Xixun
Chen, Xi
Yan, Chunling
Jiao, Jianwei
Jiao, Qian
Jiang, Hong
Ghrelin Bridges DMV Neuropathology and GI Dysfunction in the Early Stages of Parkinson's Disease
title Ghrelin Bridges DMV Neuropathology and GI Dysfunction in the Early Stages of Parkinson's Disease
title_full Ghrelin Bridges DMV Neuropathology and GI Dysfunction in the Early Stages of Parkinson's Disease
title_fullStr Ghrelin Bridges DMV Neuropathology and GI Dysfunction in the Early Stages of Parkinson's Disease
title_full_unstemmed Ghrelin Bridges DMV Neuropathology and GI Dysfunction in the Early Stages of Parkinson's Disease
title_short Ghrelin Bridges DMV Neuropathology and GI Dysfunction in the Early Stages of Parkinson's Disease
title_sort ghrelin bridges dmv neuropathology and gi dysfunction in the early stages of parkinson's disease
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9596842/
https://www.ncbi.nlm.nih.gov/pubmed/36050877
http://dx.doi.org/10.1002/advs.202203020
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