title: Short and long-term changes in cerebral [14C]-2-deoxyglucose uptake in the MPTP-treated marmoset: relationship to locomotor activity.
abstract: The "short-term" (0.7 +/- 0.1 months post-MPTP) and "long-term" effects (36.7 +/- 4.4 months) of MPTP treatment on motor behaviour and [14C]-2DG uptake were investigated in the common marmoset. The subcutaneous administration of MPTP greatly reduced locomotor activity (-94% with respect to controls) and induced motor disability in the "short-term" MPTP-treated marmoset group. In the "long-term" MPTP group, MPTP treatment did not significantly affect locomotor activity (-27% with respect to controls) and there was partial recovery of motor disability. In the "short-term" MPTP group, there were increases in [14C]-2DG uptake in the GPl (+31 to +37%), SNc (+34 to +42%), VTA (+35%), LC (+23%), PPN (+19%) and in the VA (+19%), VL (+20%) and AM (+17%) thalamic nuclei. [14C]-2DG uptake was decreased in the STN (-15%). In the "long-term" MPTP group, [14C]-2DG uptake was increased in the GPl (+18%), SNc (+27%), VTA (+25%), PPN (+19%), ventral caudate nucleus (+18 to +23%), NAc (+22%), F.Ctx (+18%) and in the VA (+34%), VL (+28%), AV (+33%) and AM (+24%) thalamic nuclei. [14C]-2DG uptake was unchanged in the STN. The increase in metabolic activity of the surviving DA neurones and/or the reactive gliosis may account for the initial increase in [14C]-2DG uptake in the SNc and VTA. On the other hand, in the "long-term" MPTP-treated animals the increase in [14C]-2DG uptake in the SNc (though less than in the "short-term" MPTP group), ventral caudate and NAc may reflect the regenerative changes in the dopaminergic system in these areas. Despite the behavioural recovery, [14C]-2DG uptake remained elevated in the target areas for medial pallidal output (the thalamic nuclei and PPN). However, the attenuation of the changes in [14C]-2DG uptake in the GPl and STN of "long-term" MPTP-treated marmosets suggest that the striato-GPl and GPl-STN outputs closely reflect motor function in this primate model of Parkinson's disease.
authors.affiliation: Parkinson's Disease Society Experimental Research Laboratories, King's College, London, United Kingdom.
authors.forename: K K
authors.initials: KK
authors.lastname: Gnanalingham
authors.forename: N A
authors.initials: NA
authors.lastname: Milkowski
authors.forename: L A
authors.initials: LA
authors.lastname: Smith
authors.forename: A J
authors.initials: AJ
authors.lastname: Hunter
authors.forename: P
authors.initials: P
authors.lastname: Jenner
authors.forename: C D
authors.initials: CD
authors.lastname: Marsden
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D000963:Antimetabolites / Q000493:pharmacokinetics*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D001931:Brain Mapping; D002144:Callithrix; D002540:Cerebral Cortex / Q000187:drug effects; D003847:Deoxyglucose / Q000493:pharmacokinetics*; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D005260:Female; D005917:Globus Pallidus / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D017072:Neostriatum / Q000187:drug effects; D013787:Thalamic Nuclei / Q000187:drug effects; D013997:Time Factors
chemical_list: D000963:Antimetabolites; D015259:Dopamine Agents; D003847:Deoxyglucose; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine