Dietary energy substrates reverse early neuronal hyperactivity in a mouse model of Alzheimer's disease

摘要: Deficient energy metabolism and network hyperactivity are the early symptoms of Alzheimer's disease (AD). In this study, we show that administration exogenous oxidative substrates (OES) corrects neuronal supply deficiency reduces amyloid-beta-induced abnormal activity in vitro epileptic phenotype AD model vivo. vitro, acute application protofibrillar amyloid-β1–42 (Aβ1–42) induced aberrant wild-type hippocampal slices was underlain by depolarization both resting membrane potential GABA-mediated current reversal potential. Aβ1–42 also impaired synaptic function long-term potentiation. These changes were paralleled clear indications metabolism, as indicated NAD(P)H signaling activity. However, when glucose supplemented with OES pyruvate 3-beta-hydroxybutyrate, failed to induce detrimental any above parameters. We administered same chronic supplementation a standard diet APPswe/PS1dE9 transgenic mice displaying AD-related epilepsy phenotype. ex-vivo slices, found subpopulations significantly depolarized potentials, mirroring abnormalities observed under Aβ1-42 application. Ex-vivo cortex fed displayed signs such strongly reduced tolerance hypoglycemia. Transgenic possessed brain glycogen levels twofold lower than those mice. none metabolic dysfunctions OES-enriched diet. vivo, dietary abated hyperexcitability, frequency epileptiform discharges spikes decreased placed on Altogether, our results suggest malfunctions underlying hyperexcitability can be prevented native substrates.