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Single X-ray irradiation modulates proteoglycan expression in brain tissue: investigation using mouse model.
Molecular Biology Reports ( IF 2.8 ) Pub Date : 2020-06-08 , DOI: 10.1007/s11033-020-05578-1
Maxim O Politko 1 , Anna I Prokaeva 1 , Oxana A Pashkovskaya 2 , Konstantin E Kuper 3 , Alexander A Zheravin 2 , Evgenii E Kliver 2 , Alexandra Y Tsidulko 1 , Svetlana V Aidagulova 4 , Elvira V Grigorieva 1
Affiliation  

Radiotherapy is an integral part of glioblastoma treatment affecting both cancer cells and tumour microenvironment, where proteoglycans (PGs) are key extracellular components. However, the molecular effects of radiotherapy on PGs expression and functional activity in brain tissue are poorly understood. Here, we aimed to study the short-term effects of X-ray irradiation on PGs expression in normal brain tissue in mouse model in vivo. Two-month-old male CBL/6Bl mice (n = 54) were used in this study, animals’ brains were irradiated using either research synchrotron VEPP-4 or clinical linear accelerator ElektaAxesse. Control (n = 18) and irradiated (n = 36) brain tissues were analysed at 24 h, 48 h and 72 h after irradiation. Morphology of the cortex and hippocampus was accessed by H&E staining, and expression of PGs (syndecan-1, glypican-1, HSPG2/perlecan, versican, brevican, neurocan, NG2/CSPG4, CD44, decorin, biglycan) was determined by RT-PCR. Single irradiation of mouse brain with a 7 Gy dose did not affect tissue morphology and mRNA levels of most highly-expressed PGs decorin and neurocan, although resulted in significant downregulation of brevican (3–10-fold) and NG2/CSPG4 (8–9-fold) expression both in cerebral cortex and subcortex. Research synchrotron and clinical linear accelerators demonstrated minor variability in their effects. Single X-ray irradiation with a 7 Gy dose does not significantly affect the mouse brain tissue morphology but selectively decreases expression levels of some PGs. The downregulation of brevican and NG2/CSPG4 but not decorin and neurocan reflects alteration of extracellular matrix in irradiated brain tissue, which might contribute to the formation of a permissive microenvironment for glioblastoma relapse development.



中文翻译:

单个X射线辐射可调节脑组织中蛋白聚糖的表达:使用小鼠模型进行调查。

放射疗法是胶质母细胞瘤治疗不可或缺的一部分,会影响癌细胞和肿瘤微环境,其中蛋白聚糖(PGs)是关键的细胞外成分。然而,对放疗对脑组织中PGs表达和功能活性的分子影响知之甚少。在这里,我们旨在研究X射线辐照对小鼠模型体内正常脑组织中PGs表达的短期影响。在这项研究中使用了两个月大的雄性CBL / 6B1小鼠(n = 54),使用研究同步加速器VEPP-4或临床线性加速器ElektaAxesse辐照了动物的大脑。对照(n = 18)和受辐照(n = 36)的脑组织分别在辐照后24 h,48 h和72 h进行分析。通过H&E染色和PG(syndecan-1,glypican-1,通过RT-PCR测定HSPG2 / perlecan,versican,brevican,neurocan,NG2 / CSPG4,CD44,decorin,biglycan)。用7 Gy剂量的单次照射小鼠大脑不会影响大多数高度表达的PG的得体和神经罐的组织形态和mRNA水平,尽管会导致灯盏花素(3-10倍)和NG2 / CSPG4(8-9显着下调)倍数)在大脑皮层和皮层下均表达。研究同步加速器和临床线性加速器显示出其效果的微小差异。剂量为7 Gy的单次X射线辐照不会显着影响小鼠脑组织形态,但会选择性降低某些PG的表达水平。brevican和NG2 / CSPG4的下调,但decorin和Neurocan的下调反映了受照射的脑组织中细胞外基质的改变,

更新日期:2020-06-08
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