STIM2 protects hippocampal mushroom spines from amyloid synaptotoxicity

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

Research output: Contribution to journalArticle

31 Scopus citations

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.

Original languageEnglish (US)
Article number37
JournalMolecular Neurodegeneration
Volume10
Issue number1
DOIs
StatePublished - Aug 15 2015

Keywords

  • Abeta peptides
  • Alzheimer disease
  • Mushroom spines
  • STIM2
  • Synapse

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Clinical Neurology
  • Molecular Biology

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