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

Völgyi, Katalin and Gulyássy, Péter and Todorov, Mihail and Puska, Gina and Badics, Kata and Kékesi, Adrienna Katalin and Czurkó, András and Drahos, László (2017) Chronic Cerebral Hypoperfusion Induced Synaptic Proteome Changes in the rat Cerebral Cortex. MOLECULAR NEUROBIOLOGY, 54. pp. 1-14. ISSN 0893-7648


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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. © 2017 Springer Science+Business Media New York

Item Type: Article
Uncontrolled Keywords: VASCULAR DEMENTIA; Synaptic proteome; Label-free LC-MS/MS; GABAergic synapse; CHRONIC CEREBRAL HYPOPERFUSION; apolipoprotein E; Alzheimer’s disease
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
R Medicine / orvostudomány > RC Internal medicine / belgyógyászat > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry / idegkórtan, neurológia, pszichiátria
Depositing User: MTMT SWORD
Date Deposited: 30 Jan 2018 14:58
Last Modified: 30 Jan 2018 14:58

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