Why do we sleep? BSF supported research has an answer
Sleep. It’s something we all do, something we all need – and something that can lead to multiple health issues for those not getting the right amount of it.
All organisms with a nervous system sleep. But the reason that animals sleep, despite continuous threats of predators, remains uncertain. As part of a BSF-supported project, Prof. Lior Appelbaum, a member of the Faculty of Life Sciences and the Gonda Multidisciplinary Brain Research Center at Bar Ilan University in Israel, partnered with Prof. Alex Keene, associate professor of biological sciences at Florida Atlantic University, to study the sleep and feeding habits of zebrafish and Mexican cave fish.
Appelbaum, the recipient of three BSF grants, has already made promising discoveries that pinpoint why sleep is so necessary. The team showed that broken DNA builds up in the brain during waking hours, and sleep is necessary to reduce this DNA damage. Appelbaum likens this to maintenance crews repairing potholes.
“Roads accumulate wear and tear, especially during the daytime, and it is most convenient and efficient to fix them at night, when there is light traffic,” he said. “With sleep, there is lighter brain input, so DNA damage can be repaired more effectively.” Earlier this year, the results were published in many scientific and media outlets, including Nature Communications, Discover Magazine, Haaretz and The Guardian.
The researchers genetically engineered small, transparent zebrafish so the chromosomes in their neurons carried colorful fluorescent tags. With the help of a powerful, specialized microscope, they watched how the chromosomes moved in the neurons, and how often DNA strands were broken, when the fish were awake and asleep. When the fish were awake, the chromosomes did not move much and broken strands of DNA built up in the neurons, as part of the normal wear and tear of life. If the fish were sleep-deprived, some of the neurons accumulated so much genetic damage they were in danger of dying off.
But when the fish fell asleep, the picture changed. The scientists noticed that the chromosomes move faster in sleeping fish and that DNA damage in their neurons plummeted. The same happened when the researchers added a sleep-inducing drug to the tank, causing the fish to fall asleep during daytime.
Appelbaum said that chromosomes are constantly changing shape to allow the cells’ natural repair mechanisms to mend DNA damage at different points.
“We’ve found a causal link between sleep, chromosome dynamics, and neuronal activity,” Appelbaum said. “All these factors affect DNA damage and repair with direct physiological relevance to the entire organism.”
The BSF team chose zebrafish for this project because of their transparency, and because their brains are simpler, yet similar, to human brains. Mexican cave fish were chosen, in part, because of their unique evolutionary biology. They live in total darkness in a small location in northeast Mexico. Though they are born with eyes, the eyes eventually fall off, leaving the fish completely blind. They have what scientists call evolved sleeplessness, meaning they require far less sleep than their river-dwelling relatives. Because of their lack of sleep, they provide a great model to study human sleep disorders such as insomnia.
Keene has been studying Mexican cave fish for many years. Though Applebaum and Keene knew of each other’s work, they barely knew one another before deciding to work together.
“We met at a conference,” Appelbaum said. “We decided very quickly that it would be good for us to work together, and since I am Israeli and he is an American, we would apply together for a BSF grant. Now, we are very close and we work together often. I am grateful to BSF for helping us to work together”.
Keene said that Applebaum’s study of zebrafish meshes well with his findings about Mexican cave fish.
“Lior has a deep background in zebrafish molecular genetics and sleep regulation and we are collaborating to apply these tools and approaches to study the evolution of sleep in our cave fish model of insomnia,” Keene said. “BSF has allowed us to meet in person and work with each other’s students. When I visited Israel last year I presented a talk on our research at the Israeli Society for Neuroscience Meeting in Eilat.”
For Appelbaum, interest in sleep came by osmosis. He started his career as a marine biologist. Then, he started exploring the mysteries of the circadian clock. In most living things, internally synchronized circadian clocks make it possible for the organism to anticipate daily environmental changes corresponding with the day–night cycle. Sleep is very much a part of this cycle.
Applebaum recently received a BSF grant through BSF’s collaboration with the U.S. National Science Foundation. He will conduct further studies on Mexican cave fish along with Erik Duboué and Johanna Kowalko of Florida Atlantic University, Nicolas Rohner of the Stowers Institute for Medical Research in Kansas City and Suzanne McGaugh of the University of Minnesota.
Though scientists are still not ready to test Appelbaum’s theories on humans, Applebaum believes they are close to this possibility. He pointed to a study conducted recently in Hong Kong, involving young, healthy doctors required to work overnight shifts. Researchers found that acute sleep deprivation and a frequently disrupted sleep cycle were associated with DNA damage – a theory similar to what Appelbaum has discovered.
“There are so many illnesses associated with sleep, or a lack of sleep,” Appelbaum said. “I hope these findings can eventually lead to more effective methods of treating sleep disorders.”