Dopamine imaging markers and predictive mathematical models for progressive degeneration in Parkinson's disease.
We conducted PET imaging studies of modulation of dopamine transporter function and MRS studies of neurochemicals in idiopathic primate Parkinson's disease (PD) model induced by long-term, low-dose administration of MPTP. MR spectra showed striking similarities of the control spectrum of the primate and human striatum as well as MPTP-treated primate (six months after cessation of MPTP), and Parkinson's disease patient striatum (68 year old male; Hoehn-Yahr scale II; 510 mg/d L-DOPA). The choline/creatine ratio was similar in the MPTP model and human parkinsonism, suggesting a possible glial abnormality. The progressive degeneration of dopamine re-uptake sites observed in our PD model can be expressed by a time dependent exponential equation N(t) = N0 exp (-(0.072 +/- 0.016) t), where N0 represents intact entities (dopamine re-uptake sites before MPTP) and 0.072 per month is the rate of degeneration. When the signs of PD appear, N(t) is about 0.3-0.4 times N0. Interestingly, this biological degenerative phenomena has similar progression to that observed in cell survival theory. According to this theory and calculated degeneration rate, predictive models can be produced for regeneration and protective treatments.
Brownell
A L
AL
Department of Radiology, Massachusetts General Hospital, Boston, USA.
Jenkins
B G
BG
Isacson
O
O
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D003042:Cocaine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis*; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism; D000882:Haplorhini; D006801:Humans; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D008297:Male; D008954:Models, Biological; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D014055:Tomography, Emission-Computed / Q000379:methods; D014793:Visual Cortex / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism
D015415:Biomarkers; D018765:Dopamine Uptake Inhibitors; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D003042:Cocaine; D004298:Dopamine