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Open Access 01-12-2015 | Research article

STIM2 protects hippocampal mushroom spines from amyloid synaptotoxicity

Authors: Elena Popugaeva, Ekaterina Pchitskaya, Anastasiya Speshilova, Sergey Alexandrov, Hua Zhang, Olga Vlasova, Ilya Bezprozvanny

Published in: Molecular Neurodegeneration | Issue 1/2015

Abstract

Background

Alzheimer disease (AD) is a disease of lost memories. Mushroom postsynaptic spines play a key role in memory storage, and loss of mushroom spines has been proposed to be linked to memory loss in AD. Generation of amyloidogenic peptides and accumulation of amyloid plaques is one of the pathological hallmarks of AD. It is important to evaluate effects of amyloid on stability of mushroom spines.

Results

In this study we used in vitro and in vivo models of amyloid synaptotoxicity to investigate effects of amyloid peptides on hippocampal mushroom spines. We discovered that application of Aβ42 oligomers to hippocampal cultures or injection of Aβ42 oligomers directly into hippocampal region resulted in reduction of mushroom spines and activity of synaptic calcium-calmodulin-dependent kinase II (CaMKII). We further discovered that expression of STIM2 protein rescued CaMKII activity and protected mushroom spines from amyloid toxicity in vitro and in vivo.

Conclusions

Obtained results suggest that downregulation of STIM2-dependent stability of mushroom spines and reduction in activity of synaptic CaMKII is a mechanism of hippocampal synaptic loss in AD model of amyloid synaptotoxicity and that modulators/activators of this pathway may have a potential therapeutic value for treatment of AD.

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Title: STIM2 protects hippocampal mushroom spines from amyloid synaptotoxicity
Authors: Elena Popugaeva
Ekaterina Pchitskaya
Anastasiya Speshilova
Sergey Alexandrov
Hua Zhang
Olga Vlasova
Ilya Bezprozvanny
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2015
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/s13024-015-0034-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

STIM2 protects hippocampal mushroom spines from amyloid synaptotoxicity

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusions

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