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Studies of Central Nervous System Cholinergic Receptors in Alzheimer’s Disease (AD)

  • Mark Watson
  • Xue Ming
  • Simi Vincent
  • Shan C. Zhang
  • John W. Culberson
  • Jennifer L. Botts
  • Zorica Jelisijevic
  • Kelvin W. Gee
Part of the Advances in Behavioral Biology book series (ABBI, volume 38A)

Abstract

Much attention has focused on changes in muscarinic acetylcholine receptors (mAChR) in AD. Binding, biochemical and radioautographic studies of human postmortem brain tissue from AD and control (C) patients have been performed. Our data suggest changes occur in mAChR subtypes on both pre- and post-synaptic neurons. Binding assays of [3H] (-)quinuclidinyl benzilate ([3H](-)QNB), a highly specific non-subtype selective antagonist, [3H](+)cis-methyldioxolane ([3H](+)CD) which labels the highest affinity mAChR agonist state, [3H]pirenzepine ([3H]PZ), a putative M1 selective mAChR antagonist, [3H]AF-DX 116 ([3H]11-2-[[2-[(diethyl-amino)methyl]-1-piperidinyl] acetyl]-5,11-dihydro-6H-pyrido-(2, 3-b) (1,4)benzodiazepine-6-one), a putative M2 antagonist, [3H]hemicholinium-3 ([3H]HC-3), an inhibitor of sodium-dependent high affinity choline uptake (SDHACU) and [3H]N-methylcarbamylcholine ([3H]MCC), a nicotinic (N) ligand, were done as described. No changes in affinity (Kd) values ere seen. Among the changes (as %C) in receptor density (Bmax) were: [3H]AF-DX 116 in temporal cortex (TC) (65); [3H]PZ in hippocamp-pus (H)(67), TC (70); [3H]HC-3 in TC (48), H (70); [3H]MCC in TC (56) and [3H] (+)CD in TC. Loss of pre-synaptic input to H and TC and an inability to up-regulate N and/or mAChR subtypes may underlie AD pathology.

Keywords

Temporal Cortex ChAT Activity Postmortem Delay Cholinergic Marker Human Postmortem Brain Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Mark Watson
    • 1
  • Xue Ming
    • 1
  • Simi Vincent
    • 1
  • Shan C. Zhang
    • 1
  • John W. Culberson
    • 1
  • Jennifer L. Botts
    • 1
  • Zorica Jelisijevic
    • 1
  • Kelvin W. Gee
    • 1
  1. 1.Dept. of Pharmacology and ToxicologyUniversity of Medicine and Dentistry of New Jersey, N.J. Medical SchoolNewarkUSA

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