Progressive Loss of Striatal Dopamine Terminals in MPTP-induced Acute Parkinsonism in Non-human Prim

来源 :第二届灵长类动物模型学术论坛暨疾病动物模型学术及战略研讨会 | 被引量 : 0次 | 上传用户:hanzedong
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  The1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine(MPTP)-induced parkinsonism model,particularly in non-human primate(NHP),remains the gold standard for the study of pathogenesis and assessment of novel therapies for Parkinsons disease(PD).However,whether the loss of dopamine neurons in this model is progressive remains controversial.This is mostly due to lacking of in vivo objective assessment of change in the integrity of dopamine neurons in live animals.In the present study,parkinsonism NHP model was induced by intravenous administration of MPTP(0.2 mg/kg)for up to 15 days and stable parkinsonism was developed for at least 90 days until the symptoms were stable.Noninvasive PET neuroimaging of vesicular monoamine transporter 2(VMAT2)with 9-[18F]fluoropropyl-(+)-dihydrotetrabenazine([18F]AV-133)was applied in NHPs before,and 15 and 90 days after acute MPTP treatment.The PET imaging results indicated that a progressive loss of striatal uptake of [18F]AV-133 was evident.The dopaminergic denervation severity(DS)showed significant linear correlation with clinical rating scores and subscores of bradykinesia.These findings demonstrated that [18F]AV-133 PET imaging could be a useful tool to noninvasively evaluate the evolution of monoaminergic terminals loss in MPTP-induced parkinsonism NHP model.
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