Synergistic Inhibition of Synaptic Signaling in Cortical Cultures by Subcytotoxic Levels of Oligomerized Amyloid-β and Iron: Alleviation by Zinc

Abstract

Iron exacerbates amyloid-β (Aβ) toxicity, while zinc alleviates it. We examined the impact of these metals on Aβ-induced signaling inhibition. Murine embryonic cortical neurons on multi-electrode arrays received 0.1 μM FeCl₂ 0.1 μM zinc acetate and/or 10 nM oligomerized Aβ_1-42. No toxicity was observed. Spontaneous signaling was not altered by iron or Aβ individually, but was inhibited by both. Zinc did not impact signaling alone, but prevented inhibition by iron plus Aβ. Aβ can be detected years before cognitive decline. Subcytotoxic iron levels may potentiate Aβ-induced impairment of synaptic activity during these early stages; zinc supplementation may alleviate this potentiation.