title: Basal ganglia cholinergic and dopaminergic function in progressive supranuclear palsy.
abstract: Progressive Supranuclear Palsy (PSP) is a progressive neurodegenerative disorder. In contrast to Parkinson's disease (PD) and dementia with Lewy bodies (DLB), replacement therapy with dopaminergic and cholinergic agents in PSP has been disappointing. The neurochemical basis for this is unclear. Our objective was to measure dopaminergic and cholinergic receptors in the basal ganglia of PSP and control brains. We measured, autoradiographically, dopaminergic (dopamine transporter, 125I PE2I and dopamine D2 receptors, 125I epidepride) and cholinergic (nicotinic alpha4beta2 receptors, 125I 5IA85380 and muscarinic M1 receptors, 3H pirenzepine) parameters in the striatum and pallidum of pathologically confirmed PSP cases (n=15) and controls (n=32). In PSP, there was a marked loss of dopamine transporter and nicotinic alpha4beta2 binding in the striatum and pallidum, consistent with loss of nigrostriatal neurones. Striatal D2 receptors were increased in the caudate and muscarinic M1 receptors were unchanged compared with controls. These results do not account for the poor response to dopaminergic and cholinergic replacement therapies in PSP, and suggest relative preservation of postsynaptic striatal projection neurones bearing D2/M1 receptors.
authors.affiliation: Institute for Ageing and Heath, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom. naomiwarren@doctors.org.uk
authors.forename: Naomi M
authors.initials: NM
authors.lastname: Warren
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Piggott
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Greally
authors.forename: Michelle
authors.initials: M
authors.lastname: Lake
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lees
authors.forename: David J
authors.initials: DJ
authors.lastname: Burn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001345:Autoradiography / Q000379:methods; D001384:Azetidines / Q000493:pharmacokinetics; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D009662:Nortropanes / Q000493:pharmacokinetics; D010890:Pirenzepine / Q000493:pharmacokinetics; D011180:Postmortem Changes; D011877:Radionuclide Imaging; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*; D013494:Supranuclear Palsy, Progressive / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: C104288:A 85380; D001384:Azetidines; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; C113010:N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane; D009662:Nortropanes; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D014316:Tritium; D010890:Pirenzepine