Impairment of muscarinic transmission in transgenic APPswe/PS1dE9 mice.
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
E
Department of Neurochemistry, Institute of Physiology CAS, Vídenská 1083, 14220 Prague 4, Czech Republic.
Jakubík
J
J
Michal
P
P
Oksman
M
M
Iivonen
H
H
Tanila
H
H
Dolezal
V
V
D000110:Acetylcholinesterase / Q000378:metabolism; D000367:Age Factors; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D004305:Dose-Response Relationship, Drug; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D051379:Mice; D009154:Mutation; D019832:N-Methylscopolamine / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D053764:Presenilin-1 / Q000235:genetics*; D011485:Protein Binding / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000378:metabolism*; D009435:Synaptic Transmission / Q000235:genetics*; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D010880:Piperidines; D053764:Presenilin-1; D011976:Receptors, Muscarinic; C493460:Slc18a3 protein, mouse; D050494:Vesicular Acetylcholine Transport Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C006189:vesamicol; D000110:Acetylcholinesterase; D019832:N-Methylscopolamine