File(s) under permanent embargo
a7-Nicotinic acetylcholine receptors mediate an A71-42-induced increase in the level of acetylcholinesterase in primary cortical neurones
journal contributionposted on 2004-03-01, 00:00 authored by L Fodero, S Mok, D Losic, L Martin, M Aguilar, Colin BarrowColin Barrow, B Livett, D Small
The β-amyloid protein (Aβ) 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 Aβ have suggested that this increase may be due to a direct action of Aβ on AChE expression in cells adjacent to amyloid plaques. The aim of the present study was to examine the mechanism by which Aβ increases levels of AChE in primary cortical neurones. Aβ1−42 was more potent than Aβ1−40 in its ability to increase AChE in primary cortical neurones. The increase in AChE was unrelated to the toxic effects of the Aβ peptides. The effect of Aβ1−42 on AChE was blocked by inhibitors of α7 nicotinic acetylcholine receptors (α7 nAChRs) as well as by inhibitors of L- or N-type voltage-dependent calcium channels (VDCCs), whereas agonists of α7 nAChRs (choline, nicotine) increased the level of AChE. The results demonstrate that the effect of Aβ1−42 on AChE is due to an agonist effect of Aβ1−42 on the α7 nAChR.