Relevance of different striatal markers in assessment of the MPP+-induced dopaminergic nigrostriatal injury in rat.
Many striatal dopaminergic markers are available for estimating the degree of the nigrostriatal lesion by MPTP/MPP+, but the changes of these markers are not perfectly matched. In this study we investigated different striatal markers and determined which ones closely reflected the nigrostriatal alteration. The in vivo binding of (E)-N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3beta-(4'-methylphenyl)nortropane (PE2I), a selective and potent inhibitor of the neuronal dopamine transporter (DAT) was considered as the reference index of injury of striatal dopaminergic nerve-endings. Rats received a 10-microg MPP+ injection in the right substantia nigra and were killed at 7 days after lesion. The results were as follows: (i) a decrease (66%) of the biodistribution of [125I]PE2I; (ii) a great reduction of the DAT expression measured by the binding of [125I]PE2I in striatal membranes (Bmax decreased by 54%) and in cerebral slices (88%); (iii) an 80% inhibition of the vesicular monoamine transporter expression revealed by the binding of [3H]dihydrotetrabenazine in cerebral slices; (iv) a robust decrease in the quantity of DA and its metabolites (about 50-60%); (v) a slight modification of the DAT activity with a decreased number of functional sites (Vmax decreased by 12%, p < 0.05) without change of the affinity in striatal synaptosomes. Among these markers the binding of [125I]PE2I in membrane homogenates and the content of DA, and its metabolites, in striatum could be the most relevant in vitro indexes of the degenerative state of the nigrostriatal pathway after MPP+ lesion.
Barc
Stéphanie
S
Groupe d'Etudes des Mécanismes Cellulaires de l'Ischémie GEMCI, EA 1223, Poitiers, France. guylene.page@univ-poitiers.fr
Page
Guylène
G
Barrier
Laurence
L
Garreau
Lucette
L
Guilloteau
Denis
D
Fauconneau
Bernard
B
Chalon
Sylvie
S
D000818:Animals; D015415:Biomarkers; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002540:Cerebral Cortex / Q000737:chemistry; D003342:Corpus Striatum / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D020267:MPTP Poisoning / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009662:Nortropanes / Q000493:pharmacokinetics; D009924:Organ Culture Techniques; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D013574:Synaptosomes / Q000737:chemistry; D014316:Tritium; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D015415:Biomarkers; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; C113010:N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009662:Nortropanes; D019275:Radiopharmaceuticals; C493216:Slc6a3 protein, rat; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D014316:Tritium; D004298:Dopamine