Disruption of Bmal1 Impairs Blood–Brain Barrier Integrity via Pericyte Dysfunction

• DOI: 10.1523/jneurosci.3639-16.2017
• Publication Date: 2017-09-15T00:11:09Z
• Authors: Ryota Nakazato; Kenji Kawabe; Daisuke Yamada; Shinsuke Ikeno; Michihiro Mieda; Shigeki Shimba; Eiichi Hinoi; Yukio Yoneda; Takeshi Takarada
• Keywords: Pericyte

Circadian rhythm disturbances are well established in neurological diseases. However, how these disruptions cause homeostatic imbalances remains poorly understood. Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) is a major circadian clock transcriptional activator, Bmal1 deficiency male Bmal1nestin-/- mice induced marked astroglial activation without affecting the number of astrocytes brain spinal cord. deletion caused blood-brain barrier (BBB) hyperpermeability with an age-dependent loss pericyte coverage blood vessels brain. Using Nestin-green fluorescent (GFP) transgenic mice, we determined that pericytes Nestin-GFP+ adult dysfunction, including downregulation platelet-derived growth factor β (PDGFRβ), necessary for maintaining BBB integrity. Knockdown downregulated PDGFRβ transcription cell line. Thus, component maintains integrity via regulating pericytes.SIGNIFICANCE STATEMENT may play role neurodegenerative disorders, such as Alzheimer's disease. Our results revealed one components by vascular-embedded pericytes. These cells were recently identified vital control permeability cerebral flow. present study demonstrates involvement homeostasis highlights dysfunction multiple