Hostname: page-component-848d4c4894-nr4z6 Total loading time: 0 Render date: 2024-05-14T15:09:40.796Z Has data issue: false hasContentIssue false
  • English
  • Français

Cholinergic Receptors in Cognitive Disorders

Published online by Cambridge University Press:  18 September 2015

E.K. Perry ,
R.H. Perry ,
C.J. Smith ,
D. Purohit ,
J. Bonham ,
D.J. Dick ,
J.M. Candy ,
J.A. Edwardson  and
A. Fairbairn
E.K. Perry*
Affiliation:
Department of Neuropathology, Newcastle General Hospital, Newcastle Upon Tyne, U.K.
R.H. Perry
Affiliation:
Department of Neuropathology, Newcastle General Hospital, Newcastle Upon Tyne, U.K.
C.J. Smith
Affiliation:
Department of Neuropathology, Newcastle General Hospital, Newcastle Upon Tyne, U.K.
D. Purohit
Affiliation:
Department of Neuropathology, Newcastle General Hospital, Newcastle Upon Tyne, U.K.
J. Bonham
Affiliation:
Department of Pathology, Newcastle General Hospital, Newcastle Upon Tyne, U.K.
D.J. Dick
Affiliation:
Regional Neurological Centre, Newcastle General Hospital, Newcastle Upon Tyne, U.K.
J.M. Candy
Affiliation:
MRC Neuroendocrinology Unit, Newcastle General Hospital, Newcastle Upon Tyne, U.K.
J.A. Edwardson
Affiliation:
MRC Neuroendocrinology Unit, Newcastle General Hospital, Newcastle Upon Tyne, U.K.
A. Fairbairn
Affiliation:
St. Nicholas Hospital, Newcastle General Hospital, Newcastle Upon Tyne, U.K.
*
Department of Neuropathology, Newcastle General Hospital, Newcastle Upon Tyne, U.K.
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Cholinergic receptors (muscarinic subtypes M1 and M2, and putative nicotinic binding) have been examined in the hippocampus obtained at autopsy from a variety of patients with cognitive disorders (Alzheimer's, Parkinson's, and Huntington's diseases, Down's Syndrome and alcoholic dementia) and compared with neurologically normal controls and cases of Motor Neuron disease. In all of the disorders associated with a pre-synaptic cortical cholinergic deficit reflected by an extensive loss of choline acetyltransferase (Alzheimer's disease, Parkinson's disease and Down's Syndrome) there was a substantial reduction in the binding of (3H) nicotine to the nicotinic receptor. By contrast reductions in both muscarinic subtypes (M1 and M2) were apparent to only a moderate extent in Alzheimer's disease, whereas in Parkinson's disease binding was significantly increased (apparently not in relation to anti-cholinergic drug treatment) in the non-demented but not demented cases. A further abnormality detected in Alzheimer's disease but not the other disorders investigated was a decrease in an endogenous inhibitor of nicotinic binding, the identity of which is as yet unknown but which may be a candidate for a possible endogenous modulator of the nicotinic receptor. These observations suggest that in Alzheimer's disease not only muscarinic but also nicotinic receptor function should be considered in relation both to future therapeutic strategies and, in the search for a clinical marker which might be of diagnostic value, to potential probes of the cortical cholinergic system.

Type
Biochemical Studies
Information
Canadian Journal of Neurological Sciences , Volume 13 , Issue S4 , November 1986 , pp. 521 - 527
Copyright
Copyright © Canadian Neurological Sciences Federation 1986

References

1.Perry, EK. The Cholinergic hypothesis - ten years on. Brit Med Bull 1986; 42: 63–69.CrossRefGoogle Scholar
2.Perry, EK, Perry, RH, Blessed, G, Tomlinson, BE.Necropsy evi-dence of central cholinergic deficits in senile dementia. Lancet 1977; 1: 189.CrossRefGoogle Scholar
3.Davies, P, Verth, AH.Regional distribution of muscarinic acetylcho- line receptor in normal and Alzheimer’s type dementia brains. Brain Res 1978; 138: 385–392.CrossRefGoogle Scholar
4.Rinne, JO, Rinne, JK, Laasko, K, Paijarvi, L, Rinne, UK. Reduction in muscarinic receptor binding in limbic areas of Alzheimer brain. J Neurol Neurosurg Psychiat 1984; 47: 651–653.CrossRefGoogle ScholarPubMed
5.Cauldfield, MP, Straughan, DW, Cross, AJ, Crow, T, Birdsall, NJM.Cortical muscarinic receptor subtypes and Alzheimer’s disease. Lancet 1982; 2: 1277.CrossRefGoogle Scholar
6.Mash, DC, Flynn, DD, Potter, LT.Loss of M2 muscarinic receptors in the cerebral cortex in Alzheimer’s disease and experimental cholinergic denervation. Science 1985; 228: 115–117.CrossRefGoogle ScholarPubMed
7.Candy, JM, Johnson, M, Perry, EK, Perry, RH, Smith, C.Hippocampal cholinergic muscarinic and putative nicotinic receptors in human cognitive disorders. Brit J Pharmac 1986 (in press).Google Scholar
8.Holman, BL, Gibson, RE, Hill, TC, Eckelman, WC, Albert, M, Reva, RC. Muscarinic acetylcholine receptors in Alzheimer’s disease. JAMA 1985; 254: 3063–3066.CrossRefGoogle ScholarPubMed
9.Oswald, RE, Freeman, JA.Alpha-bungarotoxin binding and central nervous system nicotinic acetylcholine receptors. Neurosci 1981; 6: 1–y.CrossRefGoogle ScholarPubMed
10.Clarke, PBS, Schwartz, RD, Paul, SM, Pert, CB, Pert, A.Nicotinic binding in rat brain; autoradiographic comparison of (3H) acetylcholine, (3H) nicotine and (1211)α-alpha-bungarotoxin. J Neurosci 1985; 5: 1307–1315.CrossRefGoogle Scholar
11.Boulter, J, Evans, K, Goldman, D, Martin, G, Treco, D, Heinemann, S, Patrick, J.Isolation of a cDNA clone coding for a possible neural nicotinic acetylcholine receptor ct-subunit. Nature 1986; 319; 368–374.CrossRefGoogle Scholar
12.Davies, P, Feisullin, S.Postmortem stability of a-bungarotoxin binding sites in mouse and human brain. Brain Res 1981; 216; 449–454.CrossRefGoogle Scholar
13.Lang, W, Henke, H.Cholinergic receptor binding and autoradiogra- phy in brains of non-neurological and senile dementia of Alzheimer-type patients. Brain Res 1983; 267: 271–280.CrossRefGoogle Scholar
14.Shimohama, S, Taniguchi, T, Fujiwara, M, Kameyama, M.Changes in nicotinic and muscarinic cholinergic receptors in Alzheimer type dementia. J Neurochem 1986; 46: 288–293.CrossRefGoogle ScholarPubMed
15.Whitehouse, PJ, Martino, AM, Antuono, PG, Lowenstein, PR, Coyle, JT, Price, DL, Kellar, KJ.Nicotinic acetylcholine binding sites in Alzheimer disease. Brain Res 1986; 371: 146–151.CrossRefGoogle Scholar
16.Wisniewski, KE, Dalton, AJ, Crapper McLachlan, DR, Wen, GY, Wisniewski, HM.Alzheimer’s disease in Down’s Syndrome; Clinicopathological studies. Neurol 1985; 35: 957–961.CrossRefGoogle Scholar
17.Olton, DS.Memory functions and the hippocampus. In: Neurobiol- ogy of the hippocampus, Seifert, W, ed. Academic Press, London 1983; 335–373.Google Scholar
18.Nicoll, RA.The septo-hippocampal projection: a model cholinergic pathway. Trends Neurosci 1985; 8: 533–536.CrossRefGoogle Scholar
19.Alonso, A, Kohler, CH.A study of the reciprocal connections between the septum and the entorhinal area using anterograde and retrograde axonal transport methods in the rat brain. Comp Neurol 1984; 225: 327–y.CrossRefGoogle ScholarPubMed
20.Blessed, G, Tomlinson, BE, Roth, M.The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Brit J Psychiat 1968; 114: 797–811.CrossRefGoogle ScholarPubMed
21.Perry, EK, Curtis, M, Dick, DJ, Candy, JM, Atack, JR, Bloxham, CA, Blessed, G, Fairbairn, A, Tomlinson, BE, Perry, RH. Cholinergic correlates of cognitive impairment in Parkinson’s disease: comparisons with Alzheimer’s disease. J Neurol Neurosurg Psychiat 1985; 48: 413–421.CrossRefGoogle ScholarPubMed
22.Watson, M, Yamamura, HI, Roeshe, WR.A unique regulatory pro- file and regional distribution of 3H-pirenzepine binding in the rat provide evidence for distinct Ml and M2 muscarinic receptor subtypes. Life Sci 1983; 32: 3001–3011.CrossRefGoogle Scholar
23.Birdsall, NJM, Burgen, ASV, Stockton, YH.Muscarinic receptor heterogeneity. Trends Pharmacol Sci 1984; suppl. (Jan.): 4–8.Google Scholar
24.Shimohama, S, Taniguchi, T, Fujiwara, M, Kameyama, M.Biochemi- cal characterization of the nicotinic cholinergic receptors in human brain: binding of (–)–3H) nicotine. J Neurochem 1985; 45: 604–610.CrossRefGoogle Scholar
25.Lowry, OH, Rosenbrough, NJ, Farr, AI, Randall, RJ.Protein mea- surement with the Folin Phenol reagent. J Biol Chem 1951; 193: 265–275.CrossRefGoogle Scholar
26.Sershen, H, Reith, MEA, Hashim, A, Lajtha, A.Endogenous mate- rial in brain inhibiting (3H) nicotine and (3H) acetylcholine binding. J Neurosci Res 1984; 12: 563–570.CrossRefGoogle Scholar
27.North, RA.Muscarinic receptors and membrane ion conductance.Trends Pharmacol Sci 1986; suppl. (Feb.): 19–22.Google Scholar
28.Perry, EK, Smith, CJ, Atack, JR, Candy, JM, Johnson, M, Perry, RH.Neocortical cholinergic enzyme and receptor activities in the human fetal brain. J Neurochem 1986 (in press).CrossRefGoogle Scholar
29.Whitehouse, PJ, Kopajtic, T, Jones, BE, Kuhar, MJ, Price, DL.An in vitro receptor autoradiographic study of muscarinic cholinergic receptor subtypes in the amygdala and neocortex of patients with Alzheimer’s disease. Neurol 1985; 35 (suppl.): 217.Google Scholar
30.De Belloroche, J, Gardiner, IM, Hamilton, MH, Birdsall, NJM. Anal- ysis of muscarinic receptor concentration and subtypes following lesion of the rat substantia innominata. Brain Res 1985; 340: 201–209.CrossRefGoogle Scholar
31.Watson, M, Vickroy, JW, Fibiger, HC, Roeske, WR, Yamamura, HI. Effects of bilateral ibotenate — induced lesions of the nucleus basalis magnocellularis upon selective cholinergic biochemical markers in the rat anterior cerebral cortex. Brain Res 1985; 346: 387–891.CrossRefGoogle ScholarPubMed
32.Yamamura, HI, Wastek, GJ, Johnson, PC, Stern, Z.Biochemical characterization of muscarinic cholinergic receptors in Huntington’s disease. Adv Behav Biol 1978; 24: 35–47.CrossRefGoogle Scholar
33.Arendt, T, Bigl, V, Arendt, A, Tennstedt, A.Loss of neurons in the nucleus basalis of Meynert in Alzheimer’s disease paralysis agitans and Korsakoff s disease. Acta Neuropath 1983: 61: 101–108.CrossRefGoogle ScholarPubMed
34.Heitanen, M, Teravainen, H.Cognitive performance in early Park- inson’s disease. Acta Neurol Scand 1986; 73: 151–y.CrossRefGoogle Scholar
35.Moss, MB, Albert, MS, Butter, SN, Payne, M. Differential patterns of memory loss among patients with Alzheimer’s disease, Huntington’s disease and alcoholic Korsakoffs Syndrome. Arch Neurol 1986; 43: 239–246.CrossRefGoogle Scholar
36.Clarke, PBS, Pert, A.Autoradiographic evidence of nicotine recep- tors on nigrostriatal and meso limbic dopaminergic neurons. Brain Res 1985; 348: 355–358.CrossRefGoogle Scholar
37.Richter, JA, Perry, EK, Tomlinson, BE.Acetylcholine and choline levels in postmortem brain tissue: preliminary observations in Alzheimer’s diseasen. Life Sci 1980; 26: 1683–1689.CrossRefGoogle Scholar
38.Quik, M, Fournier, S, Trifaro, JM. Modulation of nicotinic α-bung- arotoxin binding site in chromaffin cells in culture by a factor (s) endogenous to neuronal tissue. Brain Res 1986; 11–20.CrossRefGoogle Scholar