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α7-nicotinic acetylcholine receptors mediate an Aβ1-42-induced increase in the level of acetylcholinesterase in primary cortical neurons

Citation

Fodero, LR and Mok, SS and Losic, D and Martin, LL and Aguilar, MI and Barrow, CJ and Livett, BG and Small, DH, α7-nicotinic acetylcholine receptors mediate an Aβ1-42-induced increase in the level of acetylcholinesterase in primary cortical neurons, Journal of Neurochemistry, 88, (5) pp. 1186-1193. ISSN 0022-3042 (2004) [Refereed Article]

DOI: doi:10.1046/j.1471-4159.2003.02296.x

Abstract

The -amyloid protein (A) is the major protein component of amyloid plaques found in the Alzheimer brain. Although there is a loss of acetylcholinesterase (AChE) from both cholinergic and non-cholinergic neurones in the brain of Alzheimer patients, the level of AChE is increased around amyloid plaques. Previous studies using P19 cells in culture and transgenic mice which overexpress human A have suggested that this increase may be due to a direct action of A on AChE expression in cells adjacent to amyloid plaques. The aim of the present study was to examine the mechanism by which A increases levels of AChE in primary cortical neurones. A1-42 was more potent than A1-40 in its ability to increase AChE in primary cortical neurones. The increase in AChE was unrelated to the toxic effects of the A peptides. The effect of A1-42 on AChE was blocked by inhibitors of 7 nicotinic acetylcholine receptors (7 nAChRs) as well as by inhibitors of L- or N-type voltage-dependent calcium channels (VDCCs), whereas agonists of 7 nAChRs (choline, nicotine) increased the level of AChE. The results demonstrate that the effect of A1-42 on AChE is due to an agonist effect of A1-42 on the 7 nAChR.

Item Details

Item Type:Refereed Article
Keywords: Acetylcholinesterase; Alzheimer's disease; Amyloid; Cholinergic; Nicotinic
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Neurodegenerative Disorders Related to Ageing
Author:Small, DH (Professor David Small)
ID Code:63315
Year Published:2004
Web of Science® Times Cited:58
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-04-28
Last Modified:2010-09-16
Downloads:0

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