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α-METHYL-PREDNISOLONE NORMALIZES THE PKC MEDIATED BRAIN ANGIOGENESIS IN DYSTROPHIC MDX MICE.
Brain Research Bulletin 2019 January 32
A fraction of patients affected by Duchenne muscular dystrophy (DMD) shows mental disability as a consequence of neuronal and metabolic alteration. In this study, we evaluated the effect of α-methyl-prednisolone (PDN) on the expression of the angiogenic marker HIF 1α, VEGF and VEGFR- 2 in correlation with PKC expression in the brain of mdx mouse, an experimental model of DMD. We demonstrated that HIF 1α, VEGF and VEGFR- 2 are overexpressed in the brain of dystrophic mdx mice in parallel with an increase of PKC expression and reduction of the tight junctions Occludin leading to altered angiogenesis. Moreover, we demonstrated that PDN treatment induces a significant reduction in the HIF 1α, VEGF, VEGFR-2, and PKC mRNA and proteins levels and restores Occludin expression reducing its phosphorylation pattern. Our results suggest a new mechanism of action of PDN that through PKC suppression normalizes the angiogenesis in dystrophic mdx brains.
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