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

Hao Wu, Eric V. Brown, Nimish K. Acharya, Denah M. Appelt, Alexander Marks, Robert Nagele, Venkateswar Venkataraman

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)154-167
Number of pages14
JournalBrain research
Volume1637
DOIs
StatePublished - Apr 15 2016

Fingerprint

Blood-Brain Barrier
Knockout Mice
Autoantibodies
Permeability
Immunoglobulin G
Neurons
Brain
Microtubule-Associated Proteins
Glial Fibrillary Acidic Protein
Microglia
Protein Transport
Signal Transduction
Biomarkers
Western Blotting
Calcium
Serum
Proteins

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Molecular Biology
  • Neuroscience(all)
  • Developmental Biology

Cite this

Wu, Hao ; Brown, Eric V. ; Acharya, Nimish K. ; Appelt, Denah M. ; Marks, Alexander ; Nagele, Robert ; Venkataraman, Venkateswar. / Age-dependent increase of blood-brain barrier permeability and neuron-binding autoantibodies in S100B knockout mice. In: Brain research. 2016 ; Vol. 1637. pp. 154-167.
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Age-dependent increase of blood-brain barrier permeability and neuron-binding autoantibodies in S100B knockout mice. / Wu, Hao; Brown, Eric V.; Acharya, Nimish K.; Appelt, Denah M.; Marks, Alexander; Nagele, Robert; Venkataraman, Venkateswar.

In: Brain research, Vol. 1637, 15.04.2016, p. 154-167.

Research output: Contribution to journalArticle

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