Age-dependent increase of blood-brain barrier permeability and neuron-binding autoantibodies in S100B knockout mice

Brain Research
Hao WuVenkat Venkataraman

Abstract

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 inte...Continue Reading

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Citations

Sep 14, 2016·Journal of Neuroinflammation·Ilse PalmersVeerle Somers
Sep 29, 2017·Tissue Barriers·Conor Delaney, Matthew Campbell
Aug 29, 2020·Epilepsia·Laura AbrairaJose Álvarez-Sabín
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Feb 12, 2021·Journal of Applied Toxicology : JAT·Odia OsemwegieErnest Smith
Dec 12, 2020·Frontiers in Cellular Neuroscience·Marie-Eve TremblayAlexei Verkhratsky
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May 8, 2021·BioMed Research International·Mengke LiangZhi Geng
Dec 7, 2021·Neurological Research and Practice·Johann Philipp ZöllnerHermann Stefan

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