Gastrointestinal dysfunction and dopaminergic, cholinergic neurotransmitte changes of myenteric plexus in a rodent model of Parkinson' s disease

Abstract

Objective To observe the gastrointestinal dysfunction and the changes of dopaminergic and cholinergic neurons in the myenteric plexuses of Sprague-Dawley (SD) rats model with parkinson' s disease (PD). Methods A rat model of PD was induced by 6-hydroxydopamine (6-OHDA). The one-h fecal output, stool water content and residual solid food in the stomach at 2 h after feeding were measured.Contractile activity of isolated antrum and colon smooth muscle were recorded. Changes in tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) in the gastrointestinal myenteric plexus were studied by immunohistochemistry. Changes in TH and ChAT mRNA levels in the gastric antrum and colon tissue were determined by reverse transcription-polymerase chain reaction ( RT-PCR). Results In the 6-OHDA group, the wet weight, dry weight and water content of the feces within 1 h were (1. 047 ± 0. 124) g,(0. 812 ±0.093) g, (22.442 ±1. 180)% respectively, which were lower than in the control group (P＜0.01); The percentage of residual solid food was (72. 316 ±3. 834)% , that was higher than in the control group (P ＜0. 01); The contractile amplitude of gastric antrum and colon smooth muscle strips was (0. 824 ±0. 152) g and (1. 541 ±0. 103) g respectively, that were lower than in the control group (P ＜0.01);The average integrated absorbance values of TH-positive areas in the myenteric plexus of gastric antrum and colon tissue were 147. 74 ± 13. 92 and 150. 45 ± 10. 09 respectively, that were higher than in the control group (P ＜0. 01); There was no significant difference in ChAT immunoreactivity between 6-OHDA group (109. 36 ± 3. 37 and 104. 73 ± 5. 93) and control group ( P ＞ 0. 05); The mRNA expression levels of TH in the gastric antrum and colon tissue were 0. 662 ±0. 011 and 0. 585 ±0.012 respectively, that were lower than in the control group (P ＜ 0. 01). There was no significant difference in ChAT mRNA expression levels between 6-OHDA group (1.157 ± 0. 037 and 1.154 ± 0. 031) and control group (P ＞ 0.05). Conclusion Constipation and delayed gastric emptying of PD rats may be associated with the increase of dopamine and relative deficiency of cholinergic neurotransmitte in enteric nervous system. Key words: Parkinson's disease; Enteric nervous system; Tyrosine hydroxylase; Choline acetyltransferase