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Defining pre-synaptic nicotinic receptors regulated by beta amyloid in mouse cortex and hippocampus with receptor null mutants
Journal article   Peer reviewed

Defining pre-synaptic nicotinic receptors regulated by beta amyloid in mouse cortex and hippocampus with receptor null mutants

Tejal K. Mehta, John J. Dougherty, Jianlin Wu, Catherine H. Choi, Ghous M. Khan and Robert A. Nichols
Journal of neurochemistry, v 109(5), pp 1452-1458
Jun 2009
PMID: 19457164

Abstract

Biochemistry & Molecular Biology Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology Science & Technology
Disruption of neuronal signaling by soluble beta-amyloid has been implicated in deficits in short-term recall in the early stages of Alzheimer's disease. One potential target for beta-amyloid is the synapse, with evidence for differential interaction with both pre- and post-synaptic elements. Our previous work revealed an agonist-like action of soluble beta-amyloid (pM to nM) on isolated pre-synaptic terminals to increase [Ca2+]i, with apparent involvement of pre-synaptic nicotinic receptors. To directly establish the role of nicotinic receptors in pre-synaptic Ca2+ regulation, we investigated the pre-synaptic action of beta-amyloid on terminals isolated from mice harboring either beta 2 or alpha 7 nicotinic receptor null mutants (knockouts). Average pre-synaptic responses to beta-amyloid in hippocampal terminals of alpha 7 knockout mice were unchanged, whereas responses in hippocampal terminals from beta 2 knockout mice were strongly attenuated. In contrast, pre-synaptic responses to soluble beta-amyloid were strongly attenuated in cortical terminals from alpha 7 knockout mice but were moderately attenuated in cortical terminals from beta 2 knockout mice. The latter responses, having distinct kinetics, were completely blocked by alpha-bungarotoxin. The use of receptor null mutants thus permitted direct demonstration of the involvement of specific nicotinic receptors in pre-synaptic Ca2+ regulation by soluble beta-amyloid, and also indicated differential neuromodulation by beta-amyloid of synapses in hippocampus and cortex.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Neurosciences
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