Rescue of Aβ 1–42 ‐induced memory impairment in day‐old chick by facilitation of astrocytic oxidative metabolism: implications for Alzheimer’s disease

Administration of small oligomeric β‐amyloid (Aβ) 1–42 45 min before one‐trial bead discrimination learning in day‐old chicks abolishes consolidation of learning 30 min post‐training (Gibbs et al. Neurobiol. Aging , in press). Administration of the β 3 ‐adrenergic agonist CL316243, which specifically stimulates astrocytic but not neuronal glucose uptake, rescues Aβ impaired memory. Weakly reinforced training can be consolidated by various metabolic substrates and we have demonstrated neuronal dependence on oxidative metabolism of glucose soon after training versus astrocytic glucose dependence 20 min later. Based on these findings we examined whether different metabolic substrates were able to counteract memory inhibition by Aβ 1–42 . Although lactate, the medium‐chain fatty acid octanoate, and the ketone body β‐hydroxybutyrate consolidated weakly reinforced training when injected close to learning, none of them were able to salvage Aβ‐impaired memory; at this early time. All three metabolites and the astrocytic‐specific acetate consolidated weak learning and rescued Aβ‐impaired memory when injected 10–20 min post‐training. However, neither glucose nor insulin rescued memory when injected at 20 min. Rescue of memory by providing astrocytes with alternative substrates for oxidative metabolism suggests that Aβ 1–42 exerts its amnestic effects specifically by impairing astrocytic glycolysis.