کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5534626 1551273 2017 24 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Global gene expression changes in the prefrontal cortex of rabbits with hypercholesterolemia and/or hypertension
ترجمه فارسی عنوان
بیان ژن بالغ در قشر پیش مغلوب خرگوش ها با هیپرکلسترولمی و / یا فشار خون بالا
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
چکیده انگلیسی


- The prefrontal cortices of hypercholesterolemic rabbits were analyzed by microarray.
- Networks include proteasome, histone, insulin and cell signaling pathways.
- Increased amyloid beta peptide was found on cortical neurons.

Although many studies have identified a link between hypercholesterolemia or hypertension and cognitive deficits, till date, comprehensive gene expression analyses of the brain under these conditions is still lacking. The present study was carried out to elucidate differential gene expression changes in the prefrontal cortex (PFC) of New Zealand white rabbits exposed to hypercholesterolemia and/or hypertension with a view of identifying gene networks at risk. Microarray analyses of the PFC of hypercholesterolemic rabbits showed 850 differentially expressed genes (DEGs) in the cortex of hypercholesterolemic rabbits compared to controls, but only 5 DEGs in hypertensive rabbits compared to controls. Up-regulated genes in the PFC of hypercholesterolemic rabbits included CIDEC, ODF2, RNASEL, FSHR, CES3 and MAB21L3, and down-regulated genes included FAM184B, CUL3, LOC100351029, TMEM109, LOC100357097 and PFDN5. Comparison with our previous study on the middle cerebral artery (MCA) of the same rabbits showed many differentially expressed genes in common between the PFC and MCA, during hypercholesterolemia. Moreover, these genes tended to fall into the same functional networks, as revealed by IPA analyses, with many identical node molecules. These include: proteasome, insulin, Akt, ERK1/2, histone, IL12, interferon alpha and NFκB. Of these, PSMB4, PSMD4, PSMG1 were chosen as representatives of genes related to the proteasome for verification by quantitative RT-PCR. Results indicate significant downregulation of all three proteasome associated genes in the PFC. Immunostaining showed significantly increased number of Aβ labelled cells in layers III and V of the cortex after hypercholesterolemia and hypertension, which may be due to decreased proteasome activity and/or increased β- or γ-secretase activity. Knowledge of altered gene networks during hypercholesterolemia and/or hypertension could inform our understanding of the link between these conditions and cognitive deficits in vascular dementia or Alzheimer's disease.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 102, January 2017, Pages 33-56
نویسندگان
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