title: Selective recovery of striatal 125I-alpha-conotoxinmii nicotinic receptors after nigrostriatal damage in monkeys.
abstract: Evidence suggests that nicotinic receptors play a role in nigrostriatal function, a finding that may be relevant to Parkinson's disease. Knowledge of the conditions that regulate nicotinic receptor expression is therefore important. Previous studies showed that several different nicotinic receptors, including alpha-conotoxinMII (alpha-CtxMII)-sensitive receptors, are decreased after nigrostriatal damage. Nigrostriatal dopaminergic terminals also demonstrate a capacity for recovery after lesioning. The present experiments were therefore done to determine whether there were changes in striatal nicotinic receptors with recovery. To address this, we used two well-characterized animal models of nigrostriatal damage produced using the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Studies in mice showed that striatal 125I-alpha-CtxMII, as well as 125I-epibatidine and 125I-A85380 binding sites significantly recovered 1 month after lesioning, suggesting that alpha6* and most likely alpha4* receptors are increased. Experiments were next done in monkeys since striatal 125I-alpha-CtxMII receptors constitute a large percentage of nicotinic receptors and are more vulnerable to nigrostriatal damage in this model that closely mirrors Parkinson's disease. In monkeys allowed to recover from the toxic effects of MPTP for a 1-2 year period, there was a significant improvement in the Parkinson disability score. There was also a reversal in lesion-induced declines in striatal alpha-CtxMII-sensitive receptors, but no significant change in 125I-epibatidine and 125I-A85380 receptors. These findings suggest that alpha3*/alpha6* sites are selectively increased in monkey striatum with recovery. The present data show that recovery of 125I-alpha-CtxMII receptors occurs in parallel with the dopamine transporter, indicating that these nicotinic receptors sites are localized to presynaptic dopamine terminals in both species.
authors.affiliation: The Parkinson's Institute, Sunnyvale, CA 94089, USA.
authors.forename: A
authors.initials: A
authors.lastname: Lai
authors.forename: J
authors.initials: J
authors.lastname: Sum
authors.forename: H
authors.initials: H
authors.lastname: Fan
authors.forename: J M
authors.initials: JM
authors.lastname: McIntosh
authors.forename: M
authors.initials: M
authors.lastname: Quik
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001384:Azetidines / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism / Q000494:pharmacology; D020916:Conotoxins / Q000378:metabolism* / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D007457:Iodine Radioisotopes; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000378:metabolism* / Q000503:physiopathology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D020127:Recovery of Function / Q000502:physiology; D012453:Saimiri; D013378:Substantia Nigra / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D001384:Azetidines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D020916:Conotoxins; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011725:Pyridines; D011978:Receptors, Nicotinic; C104288:A 85380; C098872:alpha-conotoxin MII; C104518:nicotinic receptor alpha6; C082748:epibatidine