title: Amyloid beta-peptide 25-35 reduces [3H]acetylcholine release in retinal neurons. Involvement of metabolic dysfunction.
abstract: Cholinergic pathways serve important functions in learning and memory processes. The loss of basal forebrain cholinergic neurons and the presence of senile plaques composed by amyloid beta-peptide (A beta) are found in post-mortem brains of Alzheimer's disease (AD) patients. However, the role of A beta in the cholinergic dysfunction observed in AD is not yet clarified. In this study, we observed that the release of [3H]acetylcholine evoked by K(+)-depolarization was significantly lower in cells treated with A beta 25-35 peptide, than in untreated cells or in cells exposed to the reverse sequence peptide A beta 35-25. The levels of pyruvate, the substrate for pyruvate dehydrogenase, the enzyme involved in acetyl coenzyme A synthesis in the brain, which is rate-limiting for the synthesis of acetylcholine, were significantly decreased, about 40%, in A beta treated cells. A beta 25-35 did not affect choline acetyltransferase activity or [3H]choline uptake. 2-[3H]-deoxyglucose uptake was decreased when cells were exposed to A beta 25-35 or to A beta 1-40. Taken together these data suggest that an impairment of glycolysis, and the consequent decrease in pyruvate levels, may be responsible for the decrement of acetylcholine release observed in A beta treated cells, thus sustaining the hypothesis that the cholinergic dysfunction, observed in AD patients, might be associated with extracellular A beta accumulation.
authors.affiliation: Center for Neurosciences of Coimbra, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal.
authors.forename: Joana Barbosa
authors.initials: JB
authors.lastname: Melo
authors.forename: Paula
authors.initials: P
authors.lastname: Agostinho
authors.forename: Catarina Resende
authors.initials: CR
authors.lastname: Oliveira
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D002642:Chick Embryo; D009474:Neurons / Q000378:metabolism*; D010446:Peptide Fragments / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D014316:Tritium
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D014316:Tritium; D000109:Acetylcholine