| First Author | Sun JL | Year | 2019 |
| Journal | Neurobiol Aging | Volume | 84 |
| Pages | 166-177 | PubMed ID | 31629115 |
| Mgi Jnum | J:284866 | Mgi Id | MGI:6391638 |
| Doi | 10.1016/j.neurobiolaging.2019.09.005 | Citation | Sun JL, et al. (2019) Co-activation of selective nicotinic acetylcholine receptors is required to reverse beta amyloid-induced Ca(2+) hyperexcitation. Neurobiol Aging 84:166-177 |
| abstractText | Beta-amyloid (Abeta) peptide accumulation has long been implicated in the pathogenesis of Alzheimer's disease (AD). Hippocampal network hyperexcitability in the early stages of the disease leads to increased epileptiform activity and eventually cognitive decline. We found that acute application of 250 nM soluble Abeta42 oligomers increased Ca(2+) activity in hippocampal neurons in parallel with a significant decrease in activity in Abeta42-treated interneurons. A potential target of Abeta42 is the nicotinic acetylcholine receptor (nAChR). Three major subtypes of nAChRs (alpha7, alpha4beta2, and alpha3beta4) have been reported in the human hippocampus. Simultaneous inhibition of both alpha7 and alpha4beta2 nAChRs mimicked the Abeta42 effects on both excitatory and inhibitory neurons. However, inhibition of all 3 subtypes showed the opposite effect. Importantly, simultaneous activation of alpha7 and alpha4beta2 nAChRs was required to reverse Abeta42-induced neuronal hyperexcitation. We suggest co-activation of alpha7 and alpha4beta2 nAChRs is required to reverse Abeta42-induced Ca(2+) hyperexcitation. |
