Keep the Rhythm Steady: Changes to Your Body’s Rhythms Could Increase Your Risk of Neurodegenerative Disease

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Circadian rhythms are the natural internal processes that regulate our sleep-wake cycle and other physiological functions such as hormone secretion and metabolism. Maintaining healthy circadian rhythms is essential for our overall health and well-being, but modern lifestyles can make this challenging. Exposure to artificial light, shift work and irregular sleep schedules can all affect our body’s natural rhythms, which can lead to a range of health problems, including involvement in neurodegenerative disease progression, as recent research presented by Caroline Grady at the American Physiology Summit in Long Beach, California suggests.

The blood-brain barrier is formed by a network of cells that separates our circulating blood and brain. This barrier prevents unwanted substances from passing through and is incredibly important for maintaining a safe environment for the brain by regulating the volume and composition of the cerebrospinal fluid.

This fluid is produced by a small tissue in your brain called the choroid plexus. Once produced, the fluid flows through your central nervous system and is ultimately reabsorbed by the rest of your body. The brain requires a very specific microenvironment to function. When that environment is changed, a lot of problems can occur, including degeneration of the nerve cells in the brain (neurodegeneration).

This central fluid flow is crucial for maintaining the brain’s microenvironment. It has been shown to play a role in many neurodegenerative diseases and is greatly influenced by circadian rhythms.

BMAL1 is a gene that is involved in regulating the circadian rhythms in our bodies. Grady and her colleagues studied fluid control in the brain by looking at rats that didn’t have the BMAL1 gene. They found that rats without the gene had more fluid around the brain compared to animals with the gene. This led them to investigate how this gene affects the brain’s ability to get rid of the extra fluid (fluid clearance).

Rats are nocturnal and typically have higher fluid clearance during the day when they are sleeping. Surprisingly, there was no difference in the brain fluid clearance rate between the rats with and without the BMAL1 gene. However, the rats without the gene had a much more permeable or “leaky” blood-brain barrier. Rhythms in key channels involved in fluid movement and blood pressure regulation in the brain were also different. It wasn’t the fluid clearance that was altered by missing this gene, but that more fluid was entering the brain through the blood-brain barrier when the BMAL1 gene was not present.

While more research is needed, the results of Grady’s study could point toward a link between circadian rhythm disruption and the development of neurodegenerative disease. While none of us are going to be losing our BMAL1 genes anytime soon, this important study reminds us how central maintaining healthy and consistent rhythms are to our health and well-being.

Gillian Kelly is a PhD student in the Department of Medicine, Division of Nephrology, at the University of Alabama at Birmingham. Her research primarily focuses on early-life stress and the cardiovascular system. Kelly served as a meeting blogger for the 2023 American Physiology Summit.

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