image: Hypocretin, previously implicated in human narcolepsy, is expressed at higher levels in the cavefish brain (A. mexicanus). Image of Mexican cavefish and surface fish counterparts (top). Brains of surface fish (left) and cavefish (right) with wake-promoting Hypocretin protein depicted in green (bottom). view more
Credit: Alex Keene, Florida Atlantic University
Nearly all animals studied need to sleep, but little is known about why some animals sleep most of the day, while others sleep very little. As a result of living in total and permanent darkness in a small location in northeast Mexico, the eyeless, tiny blind Mexican cavefish (Astyanax mexicanus) has evolved sleeplessness, snoozing far less than their river-dwelling relatives. These fish have been studied for nearly 100 years for their fascinating traits, yet little is known about how their behavior evolves. Because of their lack of sleep, they provide a great model to study human sleep disorders such as insomnia.
A new study published in eLife by neuroscientists in the Charles E. Schmidt College of Science at Florida Atlantic University is providing new insight into the evolution of sleep.
For the study, the researchers found that the neuropeptide Hypocretin, previously implicated in human narcolepsy, is expressed at higher levels in the cavefish brain. While loss of Hypocretin has been shown to cause narcolepsy in human and animal models, cavefish evolved to have higher levels of Hypocretin resulting in sleeplessness.
"These findings suggest that differences in Hypocretin production may explain variation in sleep between animal species, or even between individual people," said Alex Keene, Ph.D., senior author and an associate professor in the Department of Biological Sciences and a member of the FAU Brain Institute. "It may also provide important insight into how we might build a brain that does not need to sleep."
The team of scientists, led by Keene, set out to uncover the mechanics behind sleep loss in A. mexicanus to find out more about how deficiencies in Hypocretin signaling are associated with altered sleep and narcolepsy, a chronic sleep disorder that causes overwhelming daytime drowsiness, in diverse vertebrate organisms.
To accomplish that, Keene and his team conducted a comparative study among A. mexicanus surface and cavefish brain cells. Their results show that the number of Hypocretin cells in cavefish is significantly higher than that of their surface-dwelling relatives.
Next, they showed that inhibiting Hypocretin signaling, genetically or pharmacologically, increased sleep in cavefish, while it had very little effect on surface fish.
"A central question moving forward is why Hypocretin functions differently in cavefish," said Keene. "We want to understand what advantage sleep loss provides these fish in the cave environment."
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Study co-authors are Erik Duboue, Ph.D., an assistant professor of biological sciences in FAU's Harriet L. Wilkes Honors College, and David Prober, Ph.D., a professor of biology at the California Institute of Technology.
"Hypocretin Underlies the Evolution of Sleep Loss in the Mexican cavefish," can be freely accessed online at https://doi.org/10.7554/eLife.32637.
This study is supported by award 25762 from the National Science Foundation to Keene.
About Florida Atlantic University:
Florida Atlantic University, established in 1961, officially opened its doors in 1964 as the fifth public university in Florida. Today, the University, with an annual economic impact of $6.3 billion, serves more than 30,000 undergraduate and graduate students at sites throughout its six-county service region in southeast Florida. FAU's world-class teaching and research faculty serves students through 10 colleges: the Dorothy F. Schmidt College of Arts and Letters, the College of Business, the College for Design and Social Inquiry, the College of Education, the College of Engineering and Computer Science, the Graduate College, the Harriet L. Wilkes Honors College, the Charles E. Schmidt College of Medicine, the Christine E. Lynn College of Nursing and the Charles E. Schmidt College of Science. FAU is ranked as a High Research Activity institution by the Carnegie Foundation for the Advancement of Teaching. The University is placing special focus on the rapid development of critical areas that form the basis of its strategic plan: Healthy aging, biotech, coastal and marine issues, neuroscience, regenerative medicine, informatics, lifespan and the environment. These areas provide opportunities for faculty and students to build upon FAU's existing strengths in research and scholarship. For more information, visit http://www.fau.edu.