Functional cholinergic damage develops with amyloid accumulation in young adult APPswe/PS1dE9 transgenic mice.
Neurobiol Dis
; 38(1): 27-35, 2010 Apr.
Article
en En
| MEDLINE
| ID: mdl-20053373
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Acetilcolina
/
Fibras Colinérgicas
/
Enfermedad de Alzheimer
/
Amiloide
/
Degeneración Nerviosa
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Neurobiol Dis
Asunto de la revista:
NEUROLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
República Checa