Chronic Cerebral Hypoperfusion Induced Synaptic Proteome Changes in the rat Cerebral Cortex

Katalin Völgyi, Péter Gulyássy, Mihail Ivilinov Todorov, Gina Puska, Kata Badics, Dávid Hlatky, Katalin Adrienna Kékesi, Gabriella Nyitrai, András Czurkó, László Drahos, Arpád Dobolyi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Chronic cerebral hypoperfusion (CCH) evokes mild cognitive impairment (MCI) and contributes to the progression of vascular dementia and Alzheimer’s disease (AD). How CCH induces these neurodegenerative processes that may spread along the synaptic network and whether they are detectable at the synaptic proteome level of the cerebral cortex remains to be established. In the present study, we report the synaptic protein changes in the cerebral cortex after stepwise bilateral common carotid artery occlusion (BCCAO) induced CCH in the rat. The occlusions were confirmed with magnetic resonance angiography 5 weeks after the surgery. Synaptosome fractions were prepared using sucrose gradient centrifugation from cerebral cortex dissected 7 weeks after the occlusion. The synaptic protein differences between the sham operated and CCH groups were analyzed with label-free nanoUHPLC-MS/MS. We identified 46 proteins showing altered abundance due to CCH. In particular, synaptic protein and lipid metabolism, as well as GABA shunt-related proteins showed increased while neurotransmission and synaptic assembly-related proteins showed decreased protein level changes in CCH rats. Protein network analysis of CCH-induced protein alterations suggested the importance of increased synaptic apolipoprotein E (APOE) level as a consequence of CCH. Therefore, the change in APOE level was confirmed with Western blotting. The identified synaptic protein changes would precede the onset of dementia-like symptoms in the CCH model, suggesting their importance in the development of vascular dementia.

Original languageEnglish
Pages (from-to)4253-4266
Number of pages14
JournalMolecular Neurobiology
Volume55
Issue number5
DOIs
Publication statusPublished - May 1 2018

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Keywords

  • Alzheimer’s disease
  • Apolipoprotein E
  • Chronic cerebral hypoperfusion
  • GABAergic synapse
  • Label-free LC-MS/MS
  • Synaptic proteome
  • Vascular dementia

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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