Journal article: Neurobiology of Aging

Evidence of impairment of muscarinic transmission in transgenic APPswe/PS1dE9 mouse model of Alzheimer´s disease.

We assessed the integrity of cholinergic neurotransmission in parietal cortex of young adult (7 months) and aged (17 months) transgenic APPswe/PS1dE9 female mice compared to littermate controls. Choline acetyltransferase and acetylcholinesterase activity declined age-dependently in both genotypes, whereas both age- and genotype-dependent decline was found in butyrylcholinesterase activity, vesicular acetylcholine transporter density, muscarinic receptors and carbachol stimulated binding of GTP gamma S in membranes as a functional indicator of muscarinic receptor coupling to G-proteins. Notably, vesicular acetylcholine transporter levels and muscarinic receptor-G-protein coupling were impaired in transgenic mice already at the age of 7 months compared to wild type littermates. Thus, brain amyloid accumulation in this mouse model is accompanied by a serious deterioration of muscarinic transmission already before the mice manifest significant cognitive deficits.
Machová, E., Jakubík, J., Michal, P., Oksman, M., Iivonen, H., Tanila, H. and Doležal, V.: Impairment of muscarinic transmission in transgenic APPswe/PS1dE9 mice. Neurobiology of Aging 2008, 29, 368-78. IF=5,607

Author: dolezalbiomed.cas.cz

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