Single X-ray irradiation modulates proteoglycan expression in brain tissue: investigation using mouse model.

Abstract

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 24h, 48h and 72h 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 7Gy 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 7Gy 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.