| Literature DB >> 29024660 |
Yanjun Zhao1, Sivaprakash Sivaji1, Michael C Chiang2, Haadi Ali1, Monica Zukowski1, Sareen Ali1, Bryan Kennedy1, Alex Sklyar1, Alice Cheng1, Zihan Guo1, Alexander K Reed1, Ravindra Kodali3, Jennifer Borowski1, Georgia Frost1, Patrick Beukema4, Zachary P Wills5.
Abstract
Compelling evidence links amyloid beta (Aβ) peptide accumulation in the brains of Alzheimer's disease (AD) patients with the emergence of learning and memory deficits, yet a clear understanding of the events that drive this synaptic pathology are lacking. We present evidence that neurons exposed to Aβ are unable to form new synapses, resulting in learning deficits in vivo. We demonstrate the Nogo receptor family (NgR1-3) acts as Aβ receptors mediating an inhibition of synapse assembly, plasticity, and learning. Live imaging studies reveal Aβ activates NgRs on the dendritic shaft of neurons, triggering an inhibition of calcium signaling. We define T-type calcium channels as a target of Aβ-NgR signaling, mediating Aβ's inhibitory effects on calcium, synapse assembly, plasticity, and learning. These studies highlight deficits in new synapse assembly as a potential initiator of cognitive pathology in AD, and pinpoint calcium dysregulation mediated by NgRs and T-type channels as key components. VIDEO ABSTRACT.Entities:
Keywords: FRET imaging; ICV injections; Nogo receptors; RCaMP sensor; RhoA2G sensor; T-type calcium channels; amyloid beta peptides; calcium dysfunction; new synapse assembly
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Year: 2017 PMID： 29024660 PMCID： PMC6101033 DOI： 10.1016/j.neuron.2017.09.041
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173