title: 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.
authors.affiliation: Center of Neurobiology and Neurodegeneration Research, Department of Biological Sciences and Biochemistry, University of Massachusetts Lowell, Lowell, MA, USA.
authors.forename: Marta Anne
authors.initials: MA
authors.lastname: Taddeo
authors.affiliation: Center of Neurobiology and Neurodegeneration Research, Department of Biological Sciences and Biochemistry, University of Massachusetts Lowell, Lowell, MA, USA.
authors.forename: Sangmook
authors.initials: S
authors.lastname: Lee
authors.affiliation: Center of Neurobiology and Neurodegeneration Research, Department of Biological Sciences and Biochemistry, University of Massachusetts Lowell, Lowell, MA, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Shea
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010446:Peptide Fragments / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D015032:Zinc / Q000008:administration & dosage*
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D007501:Iron; D015032:Zinc
keywords: Amyloid-β; iron; metal toxicity; multi-electrode arrays; signaling; zinc