Changing Of DAT, 5-HT1A Receptor And 5-HTT In The MPTP Mouse Model Of Parkinson's Disease

To investigate the local changes in dopamine transporter (DAT), serotonin transporter (5-HTT) and serotonin 1A receptor (5-HT1A) in 1-methy-4-phenyl-1, 2, 3, 6-tetrahy-dropyridine (MPTP) induced Parkinson's disease (PD) mouse model, and to explore the time- and dose-dependent manner of motor disorders in this PD mouse model.Eight-week-old male C57BL/6 mice were randomized into 3 groups, and were given intraperitoneally a total dose of 20 mg/kg (single injection), 80 mg/kg (four injections of 20 mg/kg at 2 hours intervals) MPTP and saline (as control), respectively. Stride length and pole time of every mouse in the three groups were recorded 1 day before and 1, 4, 7, 10 days after the last injection of MPTP or saline. At the 11th day, the mice were sacrificed for ex vivo autoradiography, immunohistochemistry and biodistribution studies.The specific binding of [125I]FP-CIT, [131I]ADAM and [131I]MPPI determined in different brain region of mice model brains were found decreasing with the increased doses of MPTP injected. Autoradiography of the mice model brain showed a significant reduction of DAT(80%,P<0.001),5-HTT(67%,P<0.001) and 5-HT1A(75%,P<0.001)in 80mg/kg MPTP-treated mice compared with the control group, which was consistent with immunohistochemical studies, where a significant decrease of DAT(54%,P<0.001),5-HTT (41%,P<0.001)and 5-HT1A(46%,P<0.001)were also observed. Furthermore, biodistribution studies exhibited reductions of 81% (P<0.001)in DAT,34%(P=0.324)in 5-HTT and 52% (P<0.05) in 5-HT1A compared with control. Behavioral test shows that the mice experienced a biphasic variation in stride length compared with saline group: an increase (P<0.001) and subsequent recovery in the first phase and a decrease (P<0.05) and another recovery in the second phase.These results indicated that MPTP administration in mice leads to neurodegeneration both in dopaminergic and serotonergic system. The toxicity induced by MPTP in central nervous system in mice is strongly dose-dependent. Time and MPTP-dose are important factors in behavioral test of the PD mouse model .