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Cerebral nitric oxide represses choroid plexus NF κB‐dependent gateway activity for leukocyte trafficking
Author(s) -
Baruch Kuti,
Kertser Alexander,
Porat Ziv,
Schwartz Michal
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201591468
Subject(s) - choroid plexus , biology , nitric oxide , gateway (web page) , microbiology and biotechnology , nf κb , immunology , neuroscience , central nervous system , endocrinology , signal transduction , world wide web , computer science
Chronic neuroinflammation is evident in brain aging and neurodegenerative disorders and is often associated with excessive nitric oxide ( NO ) production within the central nervous system ( CNS ). Under such conditions, increased NO levels are observed at the choroid plexus ( CP ), an epithelial layer that forms the blood–cerebrospinal fluid barrier ( BCSFB ) and serves as a selective gateway for leukocyte entry to the CNS in homeostasis and following injury. Here, we hypothesized that elevated cerebral NO levels interfere with CP gateway activity. We found that induction of leukocyte trafficking determinants by the CP and sequential leukocyte entry to the CSF are dependent on the CP epithelial NF κB/p65 signaling pathway, which was inhibited upon exposure to NO . Examining the CP in 5 XFAD transgenic mouse model of Alzheimer's disease ( AD ‐Tg) revealed impaired ability to mount an NF κB/p65‐dependent response. Systemic administration of an NO scavenger in AD ‐Tg mice alleviated NF κB/p65 suppression at the CP and augmented its gateway activity. Together, our findings identify cerebral NO as a negative regulator of CP gateway activity for immune cell trafficking to the CNS .