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

Authors: Völgyi, Katalin  Gulyássy, Péter  Todorov, Mihail Ivilinov  Puska, Gina  Badics, Kata  Hlatky, Dávid  Kékesi, Katalin Adrienna  Nyitrai, Gabriella  Czurkó, András  Drahos, László  Dobolyi, Arpád 
Citation: Völgyi K, etal., Mol Neurobiol. 2018 May;55(5):4253-4266. doi: 10.1007/s12035-017-0641-0. Epub 2017 Jun 15.
Pubmed: (View Article at PubMed) PMID:28620701
DOI: Full-text: DOI:10.1007/s12035-017-0641-0

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.


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RGD Object Information
RGD ID: 13703133
Created: 2018-08-03
Species: All species
Last Modified: 2018-08-03
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.