title: Reduced expression of choline acetyltransferase in vagal motoneurons and gastric motor dysfunction in a 6-OHDA rat model of Parkinson's disease.
abstract: Parkinson's disease (PD) has been characterized by dopaminergic neuron degeneration in the substantia nigra (SN) accompanied by pathology of the dorsal motor nucleus of the vagus (DMV). PD patients have often experienced gastrointestinal dysfunctions, such as gastroparesis. However, the mechanism underlying these symptoms in PD patients is not clear. In the present study, we investigated alterations of cholinergic and catecholaminergic neurons in the DMV and gastric motor function in rats microinjected with 6-hydroxydopamine (6-OHDA) bilaterally into the SN (referred to as 6-OHDA rats) and explored possible mechanisms. A strain gauge force transducer was used to record gastric motility in vivo. Expression of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) was evaluated by immunofluorescence and western blot analysis. Acetylcholine (Ach) content was measured using ultra-performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS) analysis. After treatment with 6-OHDA for 6weeks, 6-OHDA rats exhibited decreased ChAT and enhanced TH expression in the DMV and decreased Ach content in the gastric muscular layer. Delayed gastric emptying and impaired gastric motility in vivo were observed in 6-OHDA rats. The results of the present study indicated that decreased ChAT and enhanced TH expression in the DMV may be correlated with the development of delayed gastric emptying and impaired gastric motility, which may be partly due to the decreased Ach release from the vagus.
authors.affiliation: Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Li-Fei
authors.initials: LF
authors.lastname: Zheng
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Wang
authors.forename: Xiao-feng
authors.initials: XF
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Song
authors.forename: Feng
authors.initials: F
authors.lastname: Hong
authors.forename: Hui
authors.initials: H
authors.lastname: Lian
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Feng
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Tang
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jin-Xia
authors.initials: JX
authors.lastname: Zhu
mesh_terms: D000109:Acetylcholine; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005746:Gastric Emptying / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000150:complications*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013272:Stomach Diseases / Q000209:etiology*; D013565:Sympatholytics / Q000633:toxicity; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase; D014630:Vagus Nerve / Q000473:pathology*
chemical_list: D013565:Sympatholytics; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine; D004298:Dopamine