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Studying Sleep in Creatures Great and Small

By: Katherine Unger Baillie Published: Mar 22, 2018

Rocky, Dean Hendricks’ English Bulldog, snoozes at her feet. This breed was the subject of Hendricks’ sleep apnea research.Rocky, Dean Hendricks’ English Bulldog, snoozes at her feet. This breed was the subject of Hendricks’ sleep apnea research.

Scientists knew a lot about fruit flies by the late 1990s. But they didn’t know that flies slept.

That insight entered the scientific literature in the year 2000, thanks to Penn Vet Dean Joan Hendricks, then a professor in the Department of Clinical Studies – Philadelphia. She was spending a sabbatical year learning molecular biology techniques in the laboratory of Dr. Amita Sehgal of the Perelman School of Medicine. In doing so, she discovered that, while fruit flies’ rest periods couldn’t be measured by an electroencephalogram (EEG) test, the insects shared many similarities to what we think of as sleep.

Drosophila image provided by the CDC.Now dozens of labs use fruit flies, or Drosophila, as a model for sleep, a fact that owes a debt to Hendricks.

“There is so much power in studying sleep in fruit flies,” she said. “You can make such rapid progress when your ‘n’ is in the hundreds. You just can’t do that if your study subjects are dogs or people.”

Before she was Dean, Hendricks was an expert on sleep and sleep disorders. And though she hasn’t had a direct hand in research since she stepped into her current leadership role in 2006, her contributions to the field, through work conducted in Bulldogs and fruit flies, have endured.

“Her helping establish a Drosophila model for sleep has been transformative in the sleep field, and it’s taken off,” said Sehgal. “My lab has continued to work with the fly sleep model and gotten a lot of really good papers from it. That early work has been very fruitful indeed.”

When Hendricks was an undergraduate at Yale University in the early 1970s, the term “neuroscience” wasn’t yet widely used. But Hendricks crafted a dual major in biology and psychology to learn about the ways that the brain controlled behavior.

“I was absolutely riveted by the idea that interesting, complicated behaviors have roots in measurable, tangible biology,” she said.

Upon entering the dual VMD-PhD program at Penn Vet, she joined the lab of Dr. Adrian Morrison, now Professor Emeritus, studying the fundamental mechanisms of sleep.

Penn Vet Professor Emeritus Dr. Adrian Morrison in his lab, surrounded by equipment used in his sleep research. Dean Hendricks joined Morrison’s lab during her VMD-PhD program.Penn Vet Professor Emeritus Dr. Adrian Morrison in his lab, surrounded by equipment used in his sleep research. Dean Hendricks joined Morrison’s lab during her VMD-PhD program.

As she was finishing her degrees, researchers in the sleep field started to realize that a sleep disorder characterized by frequent snoring, long pauses in breathing while sleeping, and fatigue during waking hours appeared to be much more common than they first thought. Now sleep scientists know that the disorder—sleep apnea—affects more than half a million people around the globe.

While there were recognized risk factors for the condition, such as being male and obese, researchers were only just beginning to understand its root causes. And Hendricks saw room to contribute.

“The question was, ‘What can I do as a veterinarian, using my training and my access to animals, to have an impact on this mystery of sleep apnea?’” Hendricks recalled.

The question initially led her to a dog breed well known for their flat faces and breathing difficulties: English Bulldogs. Hendricks quickly realized that this breed, unlike others, had all the characteristics of sleep apnea.

“Every Bulldog had this problem,” Hendricks said. “They wouldn’t have apneas during the first phase of sleep, but during REM sleep, they would have pauses in breathing that lasted up to 45 seconds or a minute, and their oxygen saturation would plummet.”

Teaming with clinicians in the medical school, including Dr. Allan Pack and Dr. Sigrid Veasey, Hendricks explored the mechanical and neurological features of sleep apnea in Bulldogs—insights that seemed to make it an ideal model for translational research.

“The recordings in the Bulldogs were remarkably similar to what we see in humans,” said Veasey.

Among other insights, Hendricks and colleagues found that the Bulldogs fired the motor neurons in their airways continuously. This firing subsided when the dogs slept, leading to the apnea episodes. Other researchers later confirmed that humans with sleep apnea do the same thing.

Hendricks and Veasey went on to target the neurochemical pathways that trigger the airway neurons, testing drug combinations that could be used to keep the airway open during sleep. They weren’t able to come up with a combination that could selectively target the airway neurons, but both see it as a promising area of research.

It was around this time when Hendricks took her sabbatical, joining Sehgal’s lab and developing an interest in fruit flies. She recalled long days spent watching flies drift off and began developing criteria to define sleep that didn’t rely on EEG recordings. She noted that there were regular periods when the flies were clearly resting; that they had a reduced sensitivity to stimuli during rest; and they “made up” for lost sleep if deprived of it. In addition, she worked with colleagues to probe such areas as circadian rhythms, sleep-related gender differences, and the connection between sleep and immune system function.

Hendricks still speaks animatedly about her pioneering work in sleep research, as well as the discoveries yet to be made. “I’m curious about the molecular changes that occur with aging and how they affect sleep, and the relationship between Alzheimer’s and sleep,” she noted.

She’s glad to have highlighted how studying multiple species—and contributing her insight as a veterinarian—can be of value in making scientific breakthroughs impacting people and animals. It’s the concept of One Health in action.

“We shouldn’t get boxed into studying one kind of organism if we’re looking at a problem,” she emphasized.