Rapid, reversible impairment of synaptic signaling in cultured cortical neurons by exogenously-applied amyloid-β.

摘要: Alzheimer's disease is accompanied by the accumulation of amyloid-β (Aβ) and microtubule-associated protein tau. Aβ toxicity dependent upon its form as well concentration. Soluble oligomers, rather than fibrillar forms that comprise senile plaques, represent toxic are correlated with extent dementia. Since soluble perturbs synaptic function, we examined impact exogenously applied on signaling in neurons cultured multi-electrode arrays. We observed subcytotoxic levels (10 nm-5 μM) human Aβ1-42 perturbed transmission within hours. This perturbation suggests mild cognitive problems, perhaps undetected traditional clinical approaches, can accompany critical Aβ. effect was prevented calcium chelator BAPTA, indicating a requirement for inhibition Aβ-induced not application MK-801 or nimodipine (antagonists NMDA receptor L-type voltage-sensitive channel, respectively) suggesting may induce influx either additional channels, contained sufficient to mediate Signaling returned original 120 h after administration single dosage Aβ, 24 replacement medium fresh lacking intervention reduce at their first appearance prevent permanent neurotoxicity.