Functional cholinergic damage develops with amyloid accumulation in young adult APPswe/PS1dE9 transgenic mice

• Published in: Neurobiology of disease Vol. 38; no. 1; pp. 27 - 35
• Main Authors: Machová, Eva, Rudajev, Vladimír, Smyčková, Helena, Koivisto, Henna, Tanila, Heikki, Doležal, Vladimír
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2010; Elsevier
• Subjects: Acetylcholine - deficiency; Acetylcholine receptors (muscarinic); Acetylcholine release; Age; Age Factors; Aging - metabolism; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Alzheimer's disease; Amyloid - metabolism; Amyloid beta-Protein Precursor - genetics; Animals; beta -Amyloid; Brain - growth & development; Brain - metabolism; Brain - physiopathology; Brain Chemistry - genetics; Brain cortex; Brain slice preparation; Cerebral Cortex - growth & development; Cerebral Cortex - metabolism; Cerebral Cortex - physiopathology; Cholinergic Agonists - pharmacology; Cholinergic Fibers - metabolism; Cholinergic Fibers - pathology; Cholinergic transmission; Cortex; Deposits; Disease Models, Animal; Down-Regulation - genetics; Female; G-proteins; GTP-Binding Proteins - drug effects; GTP-Binding Proteins - genetics; GTP-Binding Proteins - metabolism; Guanine nucleotide-binding protein; Hippocampus; Hippocampus - metabolism; Hippocampus - pathology; Hippocampus - physiopathology; Mice; Mice, Transgenic; Muscarinic neurotransmission; Neostriatum; Nerve Degeneration - metabolism; Nerve Degeneration - pathology; Nervous system; Neurology; Organ Culture Techniques; Plaques; Presenilin-1 - genetics; Receptors, Muscarinic - metabolism; Striatum; Transgenic APPswe/PS1dE9 mice; Transgenic mice; Striatum; Brain cortex; Transgenic APPswe/PS1dE9 mice; Acetylcholine release; Alzheimer's disease; G-proteins; Hippocampus; Muscarinic neurotransmission
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2009.12.023

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 β-amyloid accumulation in the brain.