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The basal ganglia cholinergic neurochemistry of progressive supranuclear palsy and other neurodegenerative diseases

Lookup NU author(s): Dr Naomi Warren, Dr Margaret Piggott, Professor David Burn

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Abstract

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 cholinergic receptor status in the basal ganglia. Aim: To measure muscarinic M2 and M4 receptors in the basal ganglia in PSP. Methods: The muscarinic M2 (presynaptic) and M4 (postsynaptic) receptors in the striatum, pallidum and adjacent insular cortex were autoradiographically measured in pathologically confirmed cases of PSP (n = 18), and compared with cases of Lewy body dementias (LBDs; n = 45), Alzheimer's disease (AD; n = 39) and controls (n = 50). Results: In cases of PSP, there was a reduction in M2 and M4 receptors in the posterior caudate and putamen compared to controls, but no significant changes in the pallidum. Cases with AD showed lower M2 receptors in the posterior striatum. Groups with LBD and AD showed higher M2 binding in the insular cortex compared with controls. Conclusions: The results suggest loss of posterior striatal cholinergic interneurones in PSP, and reduction in medium spiny projection neurones bearing M4 receptors. These results should be taken in the context of more widespread pathology in PSP, but may have implications for future trials of cholinergic treatments.


Publication metadata

Author(s): Warren NM, Piggott MA, Lees AJ, Burn DJ

Publication type: Article

Publication status: Published

Journal: Journal of Neurology, Neurosurgery and Psychiatry

Year: 2007

Volume: 78

Issue: 6

Pages: 571-575

Print publication date: 01/06/2007

Date deposited: 21/06/2010

ISSN (print): 0022-3050

ISSN (electronic): 1468-330X

Publisher: BMJ Group

URL: http://dx.doi.org/10.1136/jnnp.2006.099937

DOI: 10.1136/jnnp.2006.099937

PubMed id: 17178818


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