Researchers at Okayama University have identified a link between circadian rhythm disturbance (human intrinsic day-night cycle) and brain dysfunction. A protein called Bmal1, known to play an important role in circadian rhythmicity has been shown to regulate the stability of the blood-brain barrier (BBB) as well.
The team of researchers led by Takeshi Takarada from Okayama University studied the function of Bmal1 protein in transgenic green-fluorescent-protein (GFP) mice. It was found that deletion of Bmal1 molecules in mice brain resulted in an increased activity of astrocytes, a type of brain cell that provides biochemical support to the BBB. They further observed higher-than-normal permeability of BBB due to pericyte dysfunction resulting from Bmal1 deficiency.
Pericytes are the cells that regulate capillary blood flow in the brain and are needed to sustain proper BBB function. The study depicted an altered expression of platelet-derived growth factor receptor β (PDGFRβ) proteins in pericytes due to deficiency of Bmal1 protein. This further led to the decreased pericyte coverage of blood vessels in the brain and abnormal permeability of BBB.
The work of Takarada and colleagues clearly establishes a connection between circadian rhythms and the physiological stability of the BBB through the common involvement of Bmal1 protein. This may facilitate the discovery and development of therapies for many neurodegenerative and/or psychiatric disorders related to abnormal BBB integrity.