Amyloid beta-peptide 25-35 reduces [ 3 H] acetylcholine release in retinal neurons. Involvement of metabolic dysfunction
2002; Taylor & Francis; Volume: 9; Issue: 4 Linguagem: Inglês
10.3109/13506120209114097
ISSN1744-2818
AutoresJoana Barbosa Melo, Paula Agostinho, Catarina R. Oliveira,
Tópico(s)Nicotinic Acetylcholine Receptors Study
ResumoAbstractCholinergic 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 β-peptide (Aβ) are found in post-mortem brains of Alzheimer's disease (AD) patients. However, the role of Aβ 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 Aβ25-35 peptide, than in untreated cells or in cells exposed to the reverse sequence peptide A p35-25 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, about40%, in Aβ treated cells. Aβ25-35 did not affect choline acetyltransferase activity or [3H]choline uptake. 2-[3H]-deoxyglucose uptake was decreased when cells were exposed to Aβ25-35 or to Aβ1-4Q. 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 Aβ treated cells, thus sustaining the hypothesis that the cholinergic dysfunction, observed in AD patients, might be associated with extracellular Aβ accumulation.Key Words: amyloidretinal cellsacetylcholineAlzheimer's disease
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