| Objective To explore the alteration of regional cerebral blood flow (rCBF) and glucose utilization as well as the neurotoxic effect on dopaminergic neurons in substantia nigra and dopamine transporter in striatum induced by escalating doses of neurotoxin MPTP, and its hint about the selection of imaging protocols in clinical study of PD. Methods Eight-week old male C57BL/6 mice were randomized into 4 groups receiving saline or a total dose of 20, 50, or 80 mg/kg MPTP intraperitoneally. At day 11 the mice were sacrificed for tyrosine hydroxylase-immunopositive cell counting in substantia nigra using SP immunohistochemistry. Ex vivo autoradiography was employed to measure striatal dopamine transporter loss, rCBF and glucose utilization in striatum and thalamus.Results The extents of dopamine transporter depletion and tyrosine hydroxylase-immunopositive cell loss were positively correlated (r=0.998, P <0.05) in a dose-dependent manner with respective maximum records of 79.8% (P<0.001) and 54.1% (P<0.001) noted in 80mg/kg MPTP-treated group. There were no deficits in rCBF in striatum and thalamus across testing days in all groups (P>0.2), while glucose utilization was significantly reduced in caudate/putamen and thalamus by 7.3% and 10.8% in 80 mg/kg MPTP-treated mice (P<0.05).Conclusions Dose-dependent effects of MPTP on dopaminergic neurons are prominent, making dopamine transporter the most sensitive indicator in the PD model assessment. There is no observable changes in rCBF in all groups, and slightly disturbed glucose utilization on higher doses in striatum and thalamus, which possibly mean their clinical limitation in evaluating the pathology, especially in mild PD cases.
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