Basal ganglia cholinergic and dopaminergic function in progressive supranuclear palsy.
Identifieur interne : 001C63 ( Ncbi/Curation ); précédent : 001C62; suivant : 001C64Basal ganglia cholinergic and dopaminergic function in progressive supranuclear palsy.
Auteurs : Naomi M. Warren [Royaume-Uni] ; Margaret A. Piggott ; Elizabeth Greally ; Michelle Lake ; Andrew J. Lees ; David J. BurnSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2007.
English descriptors
- KwdEn :
- Aged, Aged, 80 and over, Autoradiography (methods), Azetidines (pharmacokinetics), Basal Ganglia (drug effects), Basal Ganglia (metabolism), Basal Ganglia (radionuclide imaging), Dopamine Plasma Membrane Transport Proteins (metabolism), Female, Humans, Iodine Radioisotopes (pharmacokinetics), Male, Nortropanes (pharmacokinetics), Pirenzepine (pharmacokinetics), Postmortem Changes, Receptors, Cholinergic (metabolism), Receptors, Dopamine (metabolism), Supranuclear Palsy, Progressive (metabolism), Supranuclear Palsy, Progressive (pathology), Supranuclear Palsy, Progressive (radionuclide imaging), Tritium (pharmacokinetics).
- MESH :
- chemical , metabolism : Dopamine Plasma Membrane Transport Proteins, Receptors, Cholinergic, Receptors, Dopamine.
- chemical , pharmacokinetics : Azetidines, Iodine Radioisotopes, Nortropanes, Pirenzepine, Tritium.
- drug effects : Basal Ganglia.
- metabolism : Basal Ganglia, Supranuclear Palsy, Progressive.
- methods : Autoradiography.
- pathology : Supranuclear Palsy, Progressive.
- radionuclide imaging : Basal Ganglia, Supranuclear Palsy, Progressive.
- Aged, Aged, 80 and over, Female, Humans, Male, Postmortem Changes.
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.
DOI: 10.1002/mds.21573
PubMed: 17534953
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pubmed:17534953Le document en format XML
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<author><name sortKey="Warren, Naomi M" sort="Warren, Naomi M" uniqKey="Warren N" first="Naomi M" last="Warren">Naomi M. Warren</name>
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<author><name sortKey="Piggott, Margaret A" sort="Piggott, Margaret A" uniqKey="Piggott M" first="Margaret A" last="Piggott">Margaret A. Piggott</name>
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<author><name sortKey="Greally, Elizabeth" sort="Greally, Elizabeth" uniqKey="Greally E" first="Elizabeth" last="Greally">Elizabeth Greally</name>
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<author><name sortKey="Lake, Michelle" sort="Lake, Michelle" uniqKey="Lake M" first="Michelle" last="Lake">Michelle Lake</name>
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<author><name sortKey="Greally, Elizabeth" sort="Greally, Elizabeth" uniqKey="Greally E" first="Elizabeth" last="Greally">Elizabeth Greally</name>
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<author><name sortKey="Lake, Michelle" sort="Lake, Michelle" uniqKey="Lake M" first="Michelle" last="Lake">Michelle Lake</name>
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<author><name sortKey="Lees, Andrew J" sort="Lees, Andrew J" uniqKey="Lees A" first="Andrew J" last="Lees">Andrew J. Lees</name>
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<term>Basal Ganglia (drug effects)</term>
<term>Basal Ganglia (metabolism)</term>
<term>Basal Ganglia (radionuclide imaging)</term>
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<term>Supranuclear Palsy, Progressive (radionuclide imaging)</term>
<term>Tritium (pharmacokinetics)</term>
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<front><div type="abstract" xml:lang="en">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.</div>
</front>
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