title: Functional cholinergic damage develops with amyloid accumulation in young adult APPswe/PS1dE9 transgenic mice.
abstract: We investigated the functional characteristics of pre- and postsynaptic cholinergic transmission in APPswe/PS1dE9 double transgenic mice at a young age (7-10 weeks) before the onset of amyloid plaque formation and at adult age (5-6 months) at its onset. We compared brain slices from cerebral cortex and hippocampus with amyloid deposits to slices from striatum with no amyloid plaques by 6 months of age. In young transgenic mice we found no impairments of preformed and newly synthesized [(3)H]-ACh release, indicating intact releasing machinery and release turnover, respectively. Adult transgenic mice displayed a significant increase in preformed [(3)H]-ACh release in cortex but a decrease in hippocampus and striatum. The extent of presynaptic muscarinic autoregulation was unchanged. Evoked release of newly synthesized [(3)H]-ACh was significantly reduced in the cortex and hippocampus but unchanged in the striatum. Carbachol-induced G-protein activation in cortical membranes displayed decreased potency but normal efficacy in adult animals and no changes in young animals. These results indicate that functional pre- and postsynaptic cholinergic deficits are not present in APPswe/PS1dE9 transgenic mice before 10 weeks of age, but develop along with beta-amyloid accumulation in the brain.
authors.affiliation: Institute of Physiology CAS, Vídenská 1083, 14220 Prague 4, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Machová
authors.forename: Vladimír
authors.initials: V
authors.lastname: Rudajev
authors.forename: Helena
authors.initials: H
authors.lastname: Smycková
authors.forename: Henna
authors.initials: H
authors.lastname: Koivisto
authors.forename: Heikki
authors.initials: H
authors.lastname: Tanila
authors.forename: Vladimír
authors.initials: V
authors.lastname: Dolezal
mesh_terms: D000109:Acetylcholine / Q000172:deficiency*; D000367:Age Factors; D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000682:Amyloid / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D018679:Cholinergic Agonists / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D009924:Organ Culture Techniques; D053764:Presenilin-1 / Q000235:genetics; D011976:Receptors, Muscarinic / Q000378:metabolism
chemical_list: D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D018679:Cholinergic Agonists; D053764:Presenilin-1; D011976:Receptors, Muscarinic; D019204:GTP-Binding Proteins; D000109:Acetylcholine