| Parkinson's disease (PD) is a progressive neurodegenerative disease of mid-aged or older adults characterized by the progressive loss of nigral dopaminergic neurons. Gastrointestinal motility is very frequently disturbed in PD, manifesting chiefly as dysphagia, delayed gastric emptying and constipation. All these symptoms-constipation in particular-may precede the clinical diagnosis of PD. In the future, these symptoms might serve as useful early indicators in the premotor stage. GI dysfunctions had a huge impact on their quality of life and their occurrence in otherwise healthy people has been associated with an increased risk for PD. Gastroparesis can produce various symptoms in patients with PD and may cause erratic absorption of drugs given to treat the disorder. It is an important factor in unpredictable fluctuations. Colonic dysfunction can consist of both slowed colonic transit with consequent reduced bowel-movement frequency, and difficulty with the act of defecation itself with anorectal excessive straining and incomplete emptying. Recognition of these GI complications can lead to earlier and potentially more effective therapeutic intervention. It is well known that GI function is under control and regulation of the central nervous system (CNS) and autonomic and enteric nervous systems (ENS), and the ENS is considered to be an independent nervous system regulating GI function. It has become increasingly evident in recent years that PD is a multicentric neurodegenerative process that affects several neuronal structures outside the substantia nigra, among which is the ENS. Recent reports have shown that the lesions in the ENS occurred at a very early stage of the disease, even before the involvement of the CNS. It has been suggested that the neurochemical alterations within the enteric nervous system could be involved in the gastrointestinal dysfunction encountered by parkinsonian patients. Neurotransmitters related to PD gastrointestinal dysfunction could be involved in the intestinal dopaminergic, cholinergic and nitric oxidergic systems. In this study,6-hydroxydopamine (6-OHDA) was microinjected into one side of the nigrostriatal system of the brain to generate a PD animal model through the impairment of rats dopaminergic neurons. After PD induction, the effects of alterations in neurotransmitters from the enteric nervous system on gastrointestinal function were observed.Objective:To investigate the gastrointestinal dysfunction and the alteration of dopaminergic, nitric oxidergic, cholinergic neurotransmitters in the myenteric plexuses of a PD rat model induced by 6-hydroxydopamine (6-OHDA).Methods:A PD rat model was induced through unilateral substantia nigra administration of 6-OHDA. Four weeks later, the one-hour fecal output,the percentage of stool water content and residual solid food in the stomach 2 h after a meal were measured. Contractile activity of isolated longitudinal antrum smooth muscle strips and proximal colon segment were measured by transducer. Changes in tyrosine hydroxylase (TH), choline acetyltransferase (ChAT) and neuronal nitric oxide synthase (nNOS) in the gastric antrum and proximal colon tissue were examined by imrnunohistochemistry. Changes in TH, ChAT and nNOS mRNA levels in the gastric antrum and proximal colon tissue were determined by Reverse transcription (RT)-polymerase chain reaction(PCR).Results:In the control group, the weight of wet feces or dry feces within 1 hour, the percentage of water content and residual solid food in the stomach was (2.329+ 0.287)g, (1.384±0.232)g, (40.464±2.675)%, (42.297±2.581)%, the mean contractile amplitude of isolated longitudinal antrum smooth muscle strips and proximal colon segments was (1.713±0.03l)g, (2.745±0.114)g. Compared with control group, the weight and water content of the fecal matter of 6-OHDA group decreased(P<0.01), the percentage of residual solid food increased(P<0.01). The mean contractile amplitude of isolated longitudinal antrum smooth muscle strips and proximal colon segments were significantly lower in 6-OHDA group than those in control group (P<0.01). The average integrated optical densities of TH, nNOS-positive products in the gastric antrum and proximal colon tissue was higher in 6-OHDA group than in control group(95.32±11.72 and 98.20±4.84,87.56±7.50 and 104.11±5.22, P<0.01). There was no significant difference in ChAT immunoreactivity in the gastric antrum and colon tissue between 6-OHDA group and control group (112.02±4.94 and 104.83±4.35, P>0.05). The mRNA levels of TH and nNOS in the gastric antrum and proximal colon in 6-OHDA group were significantly increased compared with control group (0.662±0.011 and 0.585±0.012,0.746±0.012 and 0.716±0.015, P<0.01). There was no significant difference in the mRNA level of ChAT in the gastric antrum and proximal colon between 6-OHDA group and the control group (1.134±0.067 and 1.138±0.069, P>0.05).Conclusions:The delayed gastric emptying, decreased of fecal output and stool water content of PD rats may be associated with the increased of dopamine, nitric oxide and relative deficiency of cholinergic neurotransmitte in enteric nervous system. |
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