Yale Researcher Receives $1.4 Million Grant To Study the Hypocretin Cells Involved in Narcolepsy

A Yale researcher has received a $1.4 million grant to study a neurotransmitter whose loss in the brain is believed responsible for narcolepsy, an often misunderstood disease marked by an uncontrollable desire to sleep.

A Yale researcher has received a $1.4 million grant to study a neurotransmitter whose loss in the brain is believed responsible for narcolepsy, an often misunderstood disease marked by an uncontrollable desire to sleep.

“It’s profoundly debilitating,” said Anthony van den Pol, professor of neurosurgery at Yale School of Medicine. “For example, narcoleptics may go to work and, despite their best intentions to the contrary, spontaneously fall asleep, raising the ire of their employer. Then at night they may have trouble sleeping, and may suffer from hallucinations when falling asleep or waking.”

Van den Pol’s laboratory, in collaboration with colleagues at Stanford and the Scripps Research Institute, first described the hypothalamic neurotransmitter, hypocretin, in 1998. Later studies showed that patients with narcolepsy did not have any neurons in the brain to make hypocretin. More recently, van den Pol and other researchers also found that hypocretin appears to be linked to pain modulation in the spinal cord.

“Our understanding of the substantial clinical importance of this neurotransmitter within two years of the discovery of hypocretin benefited from a host of basic science discoveries. These discoveries were related to the organization and cellular physiology of the hypocretin system and were made prior to the finding that hypocretin loss leads to narcolepsy,” said Van den Pol.

Narcolepsy affects an estimated one in 2,000 Americans, about the same number as those who have Parkinson’s Disease. It often shows up in the teen years and is believed to be a lifelong problem. The sleep episodes last anywhere from a few minutes to a few hours, after which the patient wakes up feeling temporarily refreshed.

Many people who suffer from narcolepsy also have cataplexy, a sudden loss of muscle tone and temporary paralysis evoked by strong emotion, such as laughing. During attacks of cataplexy, which last a few seconds or minutes, narcoleptics are conscious of their environment, but are unable to move.

Common medications currently used include stimulants employed to keep narcoleptics alert during the day by increasing their neuronal activity. New generations of medications based on the hypocretin neurotransmitter may prove useful in future treatments of this disease and may avoid some of the side effects associated with stimulants.

The grant from the National Institute of Health will enable a focus on the electrical behavior of the nerve cells in the hypothalamus that make hypocretin. Van den Pol and colleagues in his lab, including Xiao-Bing Gao and Ying Li, cellular electrophysiologist, and Prabhat Ghosh, a molecular biologist, will use a combination of patch clamp electrical recording, ultrastructural immunocytochemistry, and molecular biology to study these nerve cells.

Van den Pol said that although hypocretin nerve cells account for only a very small percentage of the cells in the brain, they have a profound effect on behavior due to their widespread connections to many other brain regions. A key to how sleep and arousal are controlled lies in the electrical activity of the hypocretin cells.

Share this with Facebook Share this with X Share this with LinkedIn Share this with Email Print this

Media Contact

Office of Public Affairs & Communications: opac@yale.edu, 203-432-1345