Functional cholinergic damage develops with amyloid accumulation in young adult APPswe/PS1dE9 transgenic mice
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
20053373
DOI
10.1016/j.nbd.2009.12.023
PII: S0969-9961(09)00378-7
Knihovny.cz E-resources
- MeSH
- Acetylcholine deficiency MeSH
- Alzheimer Disease genetics metabolism physiopathology MeSH
- Amyloid metabolism MeSH
- Amyloid beta-Protein Precursor genetics MeSH
- Cholinergic Agonists pharmacology MeSH
- Cholinergic Fibers metabolism pathology MeSH
- Nerve Degeneration metabolism pathology MeSH
- Down-Regulation genetics MeSH
- Hippocampus metabolism pathology physiopathology MeSH
- Disease Models, Animal MeSH
- Brain Chemistry genetics MeSH
- Brain growth & development metabolism physiopathology MeSH
- Cerebral Cortex growth & development metabolism physiopathology MeSH
- Mice, Transgenic MeSH
- Mice MeSH
- Organ Culture Techniques MeSH
- Presenilin-1 genetics MeSH
- GTP-Binding Proteins drug effects genetics metabolism MeSH
- Receptors, Muscarinic metabolism MeSH
- Aging metabolism MeSH
- Age Factors MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acetylcholine MeSH
- Amyloid MeSH
- Amyloid beta-Protein Precursor MeSH
- Cholinergic Agonists MeSH
- Presenilin-1 MeSH
- GTP-Binding Proteins MeSH
- Receptors, Muscarinic MeSH
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.
References provided by Crossref.org
The Role of Lipid Environment in Ganglioside GM1-Induced Amyloid β Aggregation
Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice
Allosteric Modulation of Muscarinic Acetylcholine Receptors
