title: Intact coupling of M1 receptors and preserved M2 and M4 receptors in the cortex in progressive supranuclear palsy: contrast with other dementias.
abstract: Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterised clinically by motor and cognitive symptoms. Cholinergic dysfunction is thought to be responsible for much of the cognitive symptomatology. To date, however, cholinergic replacement therapies have been ineffective. We used receptor specific radioligand autoradiography to measure M1, M2, and M4 receptor density, and the functional status of the principal cortical subtype, M1, in the frontal cortex in post-mortem brain tissue of PSP patients (n=14). Results were compared to normal controls (n=17) and patients with dementia with Lewy bodies (DLB, n=12) and Alzheimer's disease (AD, n=15). In PSP there were no changes in M1, M2, or M4 muscarinic receptor densities or M1 coupling. DLB cases showed a non-significant increase in M1 receptors. In AD there was a reduction in M1 receptors and coupling in most frontal cortical areas which reached significance, compared to DLB, for M1 receptors in the cingulate (p<0.05). We conclude from this first systematic study of cortical muscarinic receptors in PSP that functioning cortical muscarinic receptors are preserved. A further, larger trial of cholinergic therapy, such as an M1 agonist, may be warranted.
authors.affiliation: Wolfson Research Centre, Newcastle University Institute for Ageing and Health, Campus for Ageing and Vitality, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne, UK. 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: Andrew J
authors.initials: AJ
authors.lastname: Lees
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Perry
authors.forename: David J
authors.initials: DJ
authors.lastname: Burn
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D001285:Atropine; D001345:Autoradiography; D002217:Carbachol; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology*; D003704:Dementia / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D020961:Lewy Body Disease / Q000473:pathology; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1 / Q000378:metabolism*; D043585:Receptor, Muscarinic M2 / Q000378:metabolism*; D043588:Receptor, Muscarinic M4 / Q000378:metabolism*; D012189:Retrospective Studies; D013494:Supranuclear Palsy, Progressive / Q000235:genetics* / Q000473:pathology*; D014015:Tissue Banks
chemical_list: D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043588:Receptor, Muscarinic M4; D001285:Atropine; D002217:Carbachol