title: Gastrointestinal dysfunction in a Parkinson's disease rat model and the changes of dopaminergic, nitric oxidergic, and cholinergic neurotransmitters in myenteric plexus.
abstract: This study aims to explore the gastrointestinal dysfunction and the changes of dopaminergic, nitric oxidergic, and cholinergic neurons in the myenteric plexus of a Parkinson's disease (PD) rat model. A PD rat model was induced through unilateral substantia nigra administration of 6-hydroxydopamine. Four weeks later, the feces in 1 h and residual solid food in stomach at 2 h after feeding were measured. Changes in tyrosine hydroxylase (TH) in substantial nigra, TH, choline acetyltransferase (ChAT), and neuronal nitric oxide synthase (nNOS) in gastric antrum and colon tissue were examined by immunohistochemistry. Reverse transcription (RT) polymerase chain reaction (PCR) and Western blot were used to evaluate and compare the levels of messenger RNA (mRNA) and protein expression of TH, ChAT, and nNOS in the GI tract between normal and 6-hydroxydopamine-lesioned rats. Compared with control samples, the number of TH⁺ cells in the damaged side of substantia nigra of 6-hydroxydopamine-lesioned rats decreased significantly (P < 0.01). The weight and water content of the fecal matter decreased (P < 0.01), and the percentage of residual solid food increased (P < 0.01). The average integrated optical densities of TH-positive areas in the gastric antrum and colon tissue increased significantly (P < 0.01), nNOS decreased significantly (P < 0.01), and there were no significant changes in ChAT (P > 0.05). TH and nNOS mRNA levels in the gastric antrum and proximal colon decreased (P < 0.01), there were no significant changes in ChAT mRNA levels (P > 0.05). The protein levels of TH in the GI tract were significantly increased (P < 0.01), nNOS significantly decreased (P < 0.01), and ChAT had no significant changes (P > 0.05). 6-Hydroxydopamine-lesioned rats had delayed gastric emptying and constipation that might be related to the gastrointestinal TH increase and nNOS decrease. These symptoms were not related to changes in cholinergic transmitters.
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. zhc660407@hotmail.com
authors.forename: Hong Can
authors.initials: HC
authors.lastname: Zhu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Chang Yue
authors.initials: CY
authors.lastname: Luo
authors.forename: Qian Qian
authors.initials: QQ
authors.lastname: Li
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology*; D005260:Female; D005767:Gastrointestinal Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D009197:Myenteric Plexus / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology*; D020734:Parkinsonian Disorders / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D000109:Acetylcholine; D004298:Dopamine