UNASSIGNED: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA).
UNASSIGNED: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939.
UNASSIGNED: The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.
■使用2型糖尿病(T2DM)db/db小鼠和db/m小鼠。应用Evans-BlueBBB渗透性测试和透射电子显微镜技术。通过免疫荧光和透射电子显微镜评估紧密连接蛋白。通过免疫荧光评估NG2-胶质细胞数量和信号通路。采用酶联免疫吸附试验(ELISA)检测血清中的基质金属蛋白酶-9(MMP-9)。
■在T2DMdb/db小鼠中,从16周龄开始,海马BBB通透性明显增加,紧密连接蛋白的结构发生了变化。db/db小鼠海马中NG2-胶质细胞的数量从12周龄开始在微血管周围增加。同时,海马MMP-9表达增加,血清无变化。16周龄的db/db小鼠在海马NG2-神经胶质中显示出Wnt/β-连环蛋白信号的激活。用XAV-939治疗改善了db/db小鼠海马BBB的结构和功能变化,并减少了海马NG2-胶质细胞的MMP-9分泌。还发现,通过用XAV-939处理,16周龄db/db小鼠的海马中的NG2-神经胶质中的β-连环蛋白蛋白的上调显著减轻。
■结果表明,NG2-胶质细胞可通过激活Wnt/β-catenin信号导致糖尿病BBB的结构和功能破坏,上调MMP-9,降解紧密连接蛋白。