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The basal ganglia cholinergic neurochemistry of progressive supranuclear palsy and other neurodegenerative diseases
  1. Warren NM (naomiwarren{at}
  1. Institute for Ageing and Health, United Kingdom
    1. Piggott MA (m.a.piggott{at}
    1. NCL, United Kingdom
      1. Lees AJ (alees{at}
      1. Institute of Neurology, United Kingdom
        1. Burn DJ (d.j.burn{at}
        1. Newcastle General Hospital, United Kingdom


          Background: Progressive Supranuclear Palsy (PSP) is a progressive neurodegenerative disorder involving motor and cognitive dysfunction. Currently there is no effective treatment either for symptomatic relief or disease modification. This relates, in part, to a lack of knowledge of the underlying neurochemical abnormalities, including the cholinergic receptor status in the basal ganglia.

          Aim: To measure muscarinic receptors in the basal ganglia in PSP.

          Methods: We measured, autoradiographically, the muscarinic M2 (presynaptic) and M4 (postsynaptic) receptors in the striatum, pallidum and adjacent insular cortex of pathologically confirmed cases of PSP (n=18), and compared them to cases of Lewy body dementias (LBD) (n=45), Alzheimer’s Disease (AD) (n=39) and controls (n=50).

          Results: In PSP there was a reduction in M2 and M4 receptors in the posterior caudate and putamen compared to control, but no significant changes in the pallidum. AD cases had lower M2 receptors in the posterior striatum. LBD and AD groups had higher M2 binding in the insular cortex compared to controls.

          Conclusions: The results suggest loss of posterior striatal cholinergic interneurons in PSP, and reduction of medium spiny projection neurons bearing M4 receptors. These results should be taken in context of more widespread pathology in PSP, but may have implications for future trials of cholinergic therapies.

          • basal ganglia
          • cholinergic
          • muscarinic receptors
          • progressive supranuclear palsy

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