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Basal ganglia cholinergic and dopaminergic function in progressive supranuclear palsy

Authors

  • Naomi M. Warren MD,

    Corresponding author
    1. Institute for Ageing and Heath, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
    • Wolfson Research centre, Institute for Ageing and Health, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, United Kingdom
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  • Margaret A. Piggott PhD,

    1. Institute for Ageing and Heath, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
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  • Elizabeth Greally BSc,

    1. Institute for Ageing and Heath, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
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  • Michelle Lake BSc,

    1. Institute for Ageing and Heath, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
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  • Andrew J. Lees MD,

    1. Institute for Ageing and Heath, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
    2. Sara Koe PSP Research Centre, Institute of Neurology, University College, London, United Kingdom
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  • David J. Burn MD

    1. Institute for Ageing and Heath, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
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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 α4β2 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 α4β2 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. © 2007 Movement Disorder Society

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