A novel nicotinic mechanism underlies β-amyloid-induced neurotoxicity

Qiang Liu, Xitao Xie, Sharareh Emadi, Michael R. Sierks, Jie Wu

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Abstract Loss of basal forebrain cholinergic neurons (BFCN) correlates with cognitive deficits in Alzheimer disease (AD). Our recent evidence suggests that chronic exposure to Aβ up-regulated neuronal α7-nAChRs and increased neuronal excitability in cultured hippocampal neurons. However, the impact of the up-regulated α7-nAChRs on Aβ-induced neurotoxicity remains unclear. In this study, we investigated the role of α7-nAChRs in the mediation of Aβ-induced neurotoxicity. The effects of Aβ exposure on α7-nAChRs and cytotoxicity were examined using whole-cell patch clamp recordings, atomic force microscope (AFM) imaging, immunoprecipitation, and lactate dehydrogenase (LDH) release assay in primary cultured hippocampal neurons as well as differentiated human neuroblastoma (SH-SY5Y) cells with cholinergic characteristics. We found that α7-nAChRs are necessary for Aβ-induced neurotoxicity in hippocampal neurons because chronic Aβ significantly increased LDH level in hippocampal cultures, which was prevented by either α7-nAChR antagonist methyllycaconitine (MLA) or by α7 subunit gene deletion (cultures prepared from nAChR α7 subunit KO mice), whereas β2-containing nAChR antagonist (dihydro-β-erythroidine, DhβE) or the genetic deletion of nAChR β2 subunit (cultures prepared from β2 KO mice) failed to prevent Aβ-induced toxicity. In SH-SY5Y cells, larger aggregates of Aβ preferentially up-regulated α7-nAChR expression and function accompanied by a significant decrease in cell viability. Co-treatment MLA, but not mecamylamine (MEC), prevented Aβ exposure-induced neurotoxicity. Our results suggest a detrimental role of upregulated α7-nAChRs in the mediation of Aβ-induced neurotoxicity.

Original languageEnglish (US)
Article number5834
Pages (from-to)457-463
Number of pages7
StatePublished - Oct 1 2015
Externally publishedYes


  • AD, Alzheimer disease
  • Aβ, amyloid-β
  • BFCN, basal forebrain cholinergic neurons
  • Patch clamp
  • α7-nAChRs, α7-containing nicotinic acetylcholine receptors

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience


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