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P3‐394: Acetylcholine changes the neuronal metabolic plasticity: A possible cellular mechanism of the glucose hypometabolism in Alzheimer's disease
Author(s) -
Porras Omar
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1964
Subject(s) - hypermetabolism , glutamate receptor , acetylcholine , cholinergic , deoxyglucose , glucose uptake , hippocampal formation , neuroscience , cholinergic neuron , carbohydrate metabolism , endocrinology , synaptic plasticity , biology , medicine , chemistry , biochemistry , insulin , receptor
amnesic symptoms of Alzheimer’s Disease (AD), occurring in the absence of any other clinical signs of brain injury, are likely to be due to changes in the function of a single synapse produced at least in part by amyloid(A ). Application of high concentrations of A peptides (in the nM range) impairs synaptic function in the hippocampus (Vitolo et al., 2002). However, in a recent study we found that a brief application of A at physiologically relevant concentrations (200 pM) enhances synaptic plasticity and memory without affecting basal synaptic transmission (Puzzo et al., 2007). Here, we investigated the effect of a prolonged exposure to A at physiologically relevant concentrations. Methods: Primary hippocampal neuronal cultures were examined before and after 24 hour treatment with 200 pM oligomeric A 42 by using whole-cell patch recordings and FM dyes. The results were validated in acute hippocampal slices by using whole cell recordings of evoked responses from CA1 pyramidal cells. Results: In hippocampal primary cultures, the 24 hour treatment with 200 pM A 42 significantly increased the basal frequency of spontaneous neurotransmitter release and the number of functional release sites, but blocked glutamate-induced synaptic plasticity. In accordance with results from the primary cultured neurons, a one hour application of 200 pM A 42 to acute hippocampal slices produced a delayed enhancement (after 40 minutes of exposure) of basal evoked responses in CA1 pyramidal cells. Conclusions: Our findings shed light on the early synaptic effects of A and support the view that a prolonged exposure to physiologically relevant levels of A enhances basal synaptic transmission, but leads to an impairment of synaptic plasticity.