Objective To investigate the expression of serotonin receptors of gut in Parkinson's disease model mice and to investigate the role of 5-HT4 receptor in motor ability,neurotransmitter and gut inflammation in PD model mice.Methods The mRNA of serotonin receptors(Htr1a,Htr1b,Htr1f,Htr2a,Htr2c,Htr4,Htr6 and Htr7)were detected in Parkinson's disease model mice ileum and colon by qRT-PCR.C57BL/6N mice were randomly divided into normal saline group,MPTP and GR 125487+MPTP group.The mice received intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine(MPTP)on day 1-5 for 5 consecutive days to build Parkinson's disease model.To investigate the effect of serotonin 4 receptor on Parkinson's disease model mice,the mice received intraperitoneal injection of 5-HT4 receptor antagonist GR 125487 daily for 16 consecutive days.Behavioral tests were conducted after the last treatment injection.The striatum and colon were collected after the behavioral test.Striatal dopamine and its metabolites were detected by HPLC.Protein expression levels of CD11b in colon was detected by western blot.Results Ileac and colonic Htr4 increased in MPTP group by qRT-PCR analysis,compared with saline group(P<0.05).The results of behavioral test showed that the motor ability of mice in MPTP group decreased(P<0.01),compared with saline group,while GR 125487+MPTP group mice aggravated motor dysfunction in PD mice(P<0.05).HPLC analysis showed that striatal dopamine decreased and dopamine turnover increased in MPTP group.GR 125487+MPTP group mice further decreased DA level and increased DA turnover.Western blot results showed CD11b expression in GR 125487+MPTP group was significantly higher than that in MPTP group(P<0.05).Conclusion The expression of Htr4 is abnormally changed in the gut of MPTP-induced Parkinson's disease model mice.5-HT4 receptor antagonist can exacerbate motor dysfunction,neurotransmitter loss and promote intestinal inflammation in Parkinson's disease model mice.
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