胶质纤维酸性蛋白
血脑屏障
自身抗体
基因剔除小鼠
星形胶质细胞
小胶质细胞
薄壁组织
免疫学
生物
细胞生物学
信号转导
受体
抗体
神经科学
病理
免疫组织化学
中枢神经系统
医学
炎症
生物化学
作者
Hao Wu,Eric V. Brown,Nimish K. Acharya,Denah M. Appelt,Alexander Marks,Robert G. Nagele,Venkat Venkataraman
出处
期刊:Brain Research
[Elsevier]
日期:2016-04-01
卷期号:1637: 154-167
被引量:26
标识
DOI:10.1016/j.brainres.2016.02.026
摘要
S100B is a calcium-sensor protein that impacts multiple signal transduction pathways. It is widely considered to be an important biomarker for several neuronal diseases as well as blood-brain barrier (BBB) breakdown. In this report, we demonstrate a BBB deficiency in mice that lack S100B through detection of leaked Immunoglobulin G (IgG) in the brain parenchyma. IgG leaks and IgG-binding to selected neurons were observed in S100B knockout (S100BKO) mice at 6 months of age but not at 3 months. By 9 months, IgG leaks persisted and the density of IgG-bound neurons increased significantly. These results reveal a chronic increase in BBB permeability upon aging in S100BKO mice for the first time. Moreover, coincident with the increase in IgG-bound neurons, autoantibodies targeting brain proteins were detected in the serum via western blots. These events were concurrent with compromise of neurons, increase of activated microglia and lack of astrocytic activation as evidenced by decreased expression of microtubule-associated protein type 2 (MAP2), elevated number of CD68 positive cells and unaltered expression of glial fibrillary acidic protein (GFAP) respectively. Results suggest a key role for S100B in maintaining BBB functional integrity and, further, propose the S100BKO mouse as a valuable model system to explore the link between chronic functional compromise of the BBB, generation of brain-reactive autoantibodies and neuronal dysfunctions.
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