Inflammation and the expression of dopamine and 5-HT receptors in colonic mucosa of Parkinson's rats
Zhang Yue, Li Yun, Zhang Xiaoli, Feng Xiaoyan, Quan Zhusheng, Zhu Jinxia
2018, 39(5):
685-692.
doi:10.3969/j.issn.1006-7795.2018.05.012
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Objective To report the distribution of dopamine (DA) and serotonin (5-HT) receptors in the colonic muscular layer and their potential role in the motility regulation in the Parkinson's disease (PD) model 6-hydroxydopamine (6-OHDA) rats, it is not clear their expressions in the colonic mucosa and correlation with the colonic mucosal dysfunction in the PD rats. The present study aims to investigate the distribution of DA and 5-HT receptors in the colonic mucosa, and the colonic mucosal inflammatory and permeability and the expression change of the DA and 5-HT receptors in the colonic mucosa in 6-OHDA rats. Methods Injection of 6-OHDA to the bilateral substantia nigras of rats, to make PD model (6-OHDA rats). Immunofluorescence (IF) and western blotting were used to observe the injection sites and the extent of DA neurons' injury. DA and 5-HT content was measured by high performance liquid chromatography-electrochemistry detection (HPLC-EDC). The mRNA and protein expression of DA receptors (D1, D2, D5) and 5-HT receptors (5-HT3, 5-HT4) was detected by Real-time PCR and Western blotting. Results In the 6-OHDA rats, the protein expression of tyrosine hydroxylase (the synthetic rate-limiting enzyme of dopamine) in substantia nigra was decreased (control:0.335±0.073, model:0.132±0.028, P<0.05), fecal water content was reduced[control:(0.119±0.005)%, model:(0.062±0.006)%, P<0.01] and the time of rotarod test was shortened[control:(35.330±3.148)s, model:(24.000±1.424)s, P<0.01], indicating the model is successful. Furthermore, the colonic transepithelial resistance was decreased[control:(73.750±4.024)Ω/cm2, model:(53.400±6.282)Ω/cm2, P<0.05], the mucosal fluorescein isothiocyanate (FITC)-dextran permeability was increased[at 60 minutes, control:(18.860±1.856)μg/L, model:(37.000±4.457)μg/L, P<0.01], and the TNF-α was also increased[control:(269.10±18.00)ng/g, model:(340.40±21.52)ng/g, P<0.05], suggesting a higher mucosal permeability and inflammation. In the colonic mucosa of 6-OHDA rats, the expression of D1[control:(0.728±0.132), model:(0.272±0.067), P<0.01] and D5 (control:0.721±0.036, model:0.543±0.051, P<0.05) were decreased, but the DA and 5-HT content, and the receptors D2, 5-HT3 and 5-HT4 had no significant alteration although 5-HT3 (control:0.078±0.016, model:0.103±0.034, P>0.05) had a increase tendency. Conclusion The present study demonstrates that 6-OHDA rats manifest a reduction of D1 and D5 expressions in colonic mucosa, and increase in colonic mucosal permeability and TNF-α level, which suggests a colonic mucosal inflammation. However, whether the reduction of colonic D1 and D5 is involved in the formation of mucosal inflammation in 6-OHDA rats needs to be further investigated.
