|Budget Amount *help
¥2,400,000 (Direct Cost : ¥2,400,000)
Fiscal Year 2001 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 2000 : ¥1,600,000 (Direct Cost : ¥1,600,000)
Simultaneous administration of 3-methylcholanthrene (3MC, 30 mg/kg) resulted in the significant prolongation of T_<LA> in pole test evaluating bradykinesia in C57BL mice of MPTP(40 mg/kg)-induced parkinsonism. RT-PCR analysis using total brain RNA from 3MC-treated and control mice showed that the mRNA levels of both b-type monoamine oxidase, which metabolically activates MPTP to MPP^+, and dopamine transporter, which transfers MPP_+ into neurons to elicit its neurodegenerative effect, did not change with the administration of 3MC. It is unlikely that the effect of 3MC did not reach the brain since the amount of CYP1A1 mRNA increased after treatment. Mice from the different supplier did not show prolonged T_<LA> after simultaneous administration of MPTP and 3MC, suggesting that genetic background plays an important role in the susceptibility to 3MC. These results suggested that enhanced progression of bradykinesia cannot be attributed simply to the change in expression level of some protein with the administration of 3MC. It is reported that estrogen deteriorates Parkinsonian symptoms in human. However, there are papers reporting that estrogen functions as a neuroprotectant against MPTP neurotoxicity. Therefore, it is possible that 3MC deteriorate parkinsonism by affecting the metabolism of estrogen. There is also a possibility that direct interaction between arylhydrocarbon receptor and estrogen receptor interfere with the neuroprotective effect of estrogen. Detailed study from this point of view is needed.