Impairment of muscarinic transmission in transgenic APPswe/PS1dE9 mice
| Autor: | Pavel Michal, Vladimír Doležal, Jan Jakubík, Heikki Tanila, Mari Oksman, Hennariikka Iivonen, Eva Machová |
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| Rok vydání: | 2008 |
| Předmět: |
Genetically modified mouse
Aging medicine.medical_specialty Carbachol Vesicular Acetylcholine Transport Proteins Biology Synaptic Transmission Animals Genetically Modified Amyloid beta-Protein Precursor Mice chemistry.chemical_compound Piperidines Internal medicine Vesicular acetylcholine transporter Muscarinic acetylcholine receptor Presenilin-1 medicine Muscarinic acetylcholine receptor M4 Animals Humans Butyrylcholinesterase Analysis of Variance Dose-Response Relationship Drug General Neuroscience Age Factors N-Methylscopolamine Receptors Muscarinic Choline acetyltransferase Acetylcholinesterase Endocrinology chemistry Guanosine 5'-O-(3-Thiotriphosphate) Mutation Female Neurology (clinical) Geriatrics and Gerontology Protein Binding Developmental Biology medicine.drug |
| Zdroj: | Neurobiology of Aging. 29:368-378 |
| ISSN: | 0197-4580 |
| DOI: | 10.1016/j.neurobiolaging.2006.10.029 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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