Circadian rhythm, the 24-hour biological clock governing many aspects of physiology, behavior, and disease, seems to be involved in rhythmic damage of the suprachiasmatic nucleus—“the site” of the circadian clock in the brain of mammals—when induced by neuromyelitis optica spectrum disorder (NMOSD). 

This finding could help researchers develop new approaches for treatment of the disease.

To explore the potential role of the circadian rhythm in NMOSD, a team of researchers led by Hui Zhang, PhD, from Shanxi Medical University in Taiyuan, China, assessed the expression of Connexin 43 (Cx43), which is thought to be involved in the participation of astrocytes in the circadian clock, and Bmal1, a gene that plays a central role in regulating the circadian rhythm.

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“We found that the levels of Bmal1 and Clock were significantly decreased in normal astrocytes,” the study’s authors said. Clock is another gene involved in circadian rhythm regulation.

Read more about the pathophysiology of NMOSD

When researchers activated Cx43 using linoleic acid or glutamate, they saw that the reduction of Bmal1 and Clock expression was reversed. 

On the contrary, blocking Cx43 or inhibiting the glutamate receptor led to a decrease in the expression of Bmal1 and Clock

In a reverse experiment, the researchers showed that when they knocked down the expression of Bmal1, the levels of glutamate, arginine vasopressin, and vasoactive intestinal polypeptide from neurons were dramatically reduced and the levels of Cx43 were significantly downregulated in NMOSD astrocytes with Cx43 activation or glutamate treatment.

However, knocking down Bmal1 in normal astrocytes did not change these levels when Cx43 was blocked or the glutamate receptor was inhibited.

The researchers concluded that Cx43-glutamate signaling plays a crucial role in NMOSD-induced rhythmic damage in the astrocytes of the suprachiasmatic nucleus.

The study is published in the journal Frontiers in Immunology.


Xue H, Wu M, Wang Y, Zhao Y, Zhang M, Zhang H. The circadian rhythms regulated by Cx43-signaling in the pathogenesis of neuromyelitis optica. Front Immunol. 2023;16;13:1021703. doi:10.3389/fimmu.2022.1021703