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Astrocytic laminin regulates pericyte differentiation and maintains blood brain barrier integrity

Author

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  • Yao Yao

    (Laboratory of Neurobiology and Genetics, The Rockefeller University)

  • Zu-Lin Chen

    (Laboratory of Neurobiology and Genetics, The Rockefeller University)

  • Erin H. Norris

    (Laboratory of Neurobiology and Genetics, The Rockefeller University)

  • Sidney Strickland

    (Laboratory of Neurobiology and Genetics, The Rockefeller University)

Abstract

Blood brain barrier (BBB) breakdown is not only a consequence of but also contributes to many neurological disorders, including stroke and Alzheimer’s disease. How the basement membrane (BM) contributes to the normal functioning of the BBB remains elusive. Here we use conditional knockout mice and an acute adenovirus-mediated knockdown model to show that lack of astrocytic laminin, a brain-specific BM component, induces BBB breakdown. Using functional blocking antibody and RNAi, we further demonstrate that astrocytic laminin, by binding to integrin α2 receptor, prevents pericyte differentiation from the BBB-stabilizing resting stage to the BBB-disrupting contractile stage, and thus maintains the integrity of BBB. Additionally, loss of astrocytic laminin decreases aquaporin-4 (AQP4) and tight junction protein expression. Altogether, we report a critical role for astrocytic laminin in BBB regulation and pericyte differentiation. These results indicate that astrocytic laminin maintains the integrity of BBB through, at least in part, regulation of pericyte differentiation.

Suggested Citation

  • Yao Yao & Zu-Lin Chen & Erin H. Norris & Sidney Strickland, 2014. "Astrocytic laminin regulates pericyte differentiation and maintains blood brain barrier integrity," Nature Communications, Nature, vol. 5(1), pages 1-12, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4413
    DOI: 10.1038/ncomms4413
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    Cited by:

    1. William A. Mills & AnnaLin M. Woo & Shan Jiang & Joelle Martin & Dayana Surendran & Matthew Bergstresser & Ian F. Kimbrough & Ukpong B. Eyo & Michael V. Sofroniew & Harald Sontheimer, 2022. "Astrocyte plasticity in mice ensures continued endfoot coverage of cerebral blood vessels following injury and declines with age," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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