~(125)I-β-CIT imaging study of striatal dopamine transporters in mice model of Parkinsonism

Abstract

Objective To detect the activity of striatal dopamine transporters (DAT) in lesions of different order of severity of MPTP-induced mice model of parkinsonism by autoradiography with 125I-β-CIT and to evaluate the clinical use of the β-CIT imaging for DAT detection. Methods With regard to the different duration (days) of MPTP treatment, the C57BL mice were randomly divided into 5 groups, that is MPTP 1,3,5 and 7day groups and control group treated with normal saline instead of MPTP. Two hours after intravenous administration with 125I-β-CIT of 148 kBq, the brain tissue sections were imaged by autoradiography. The levels of dopamine (DA) and its metabolites were measured by high performance liquid chromatography and electrochemical detection (HPLC-ECD). The tyrosine hydroxylase (TH)-positive cells and fibres in the substantia nigra and striatum of the mice were observed by means of immunohistochemical technique. Results As compared with control group, the radioactivity ratios of striatum to cortex (ST/CX) in 4 MPTP-treated groups were significantly reduced,by 20%, 42%, 45% and 52%,respectively. The concentrations of DA in the striatum of 4 MPTP-treated groups were remarkably decreased,by 47%, 75%, 95% and 95%,respectively. The gradual loss of DA neurons and fibres in the substantia nigra and striatum in 4 MPTP-treated groups was observed under microscopy. Conclusions The functional abnormality of DAT paralleled the changes observed in neurochemistry and neuropathology studies in the lesions of different order of injury of the MPTP-treated mice. The β-CIT scanning for the activity of DAT may be useful for diagnosing PD at earlier phase and for monitoring the progression of the disease.