Intracellular oligomeric amyloid-beta rapidly regulates GluA1 subunit of AMPA receptor in the hippocampus

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Title
Intracellular oligomeric amyloid-beta rapidly regulates GluA1 subunit of AMPA receptor in the hippocampus
Author(s)
Daniel J. Whitcomb; Ellen L. Hogg; Philip Regan; Thomas Piers; Priyanka Narayan; Garry Whitehead; Bryony L. Winters; Dong-Hyun Kim; Eunjoon Kim; Peter St George-Hyslop; David Klenerman; Gragam L. Collingridge; Jihoon Jo; Kwangwook Cho
Publication Date
2015-06
Journal
SCIENTIFIC REPORTS, v.5, no., pp.10934 -
Publisher
NATURE PUBLISHING GROUP
Abstract
The acute neurotoxicity of oligomeric forms of amyloid-beta 1-42 (A beta) is implicated in the pathogenesis of Alzheimer's disease (AD). However, how these oligomers might first impair neuronal function at the onset of pathology is poorly understood. Here we have examined the underlying toxic effects caused by an increase in levels of intracellular A beta, an event that could be important during the early stages of the disease. We show that oligomerised A beta induces a rapid enhancement of AMPA receptor-mediated synaptic transmission (EPSCA) when applied intracellularly. This effect is dependent on postsynaptic Ca2+ and PKA. Knockdown of GluA1, but not GluA2, prevents the effect, as does expression of a S8(45)-phosphomutant of GluA1. Significantly, an inhibitor of Ca2+-permeable AMPARs (CP-AMPARs), IEM 1460, reverses the increase in the amplitude of EPSCA. These results suggest that a primary neuronal response to intracellular A beta oligomers is the rapid synaptic insertion of CP-AMPARs
URI
https://pr.ibs.re.kr/handle/8788114/1739
ISSN
2045-2322
Appears in Collections:
Center for Synaptic Brain Dysfunctions(시냅스 뇌질환 연구단) > Journal Papers (저널논문)
Files in This Item:
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