|
Press Release
Narcolepsy may be Due to Loss of Brain Cells
For immediate release September 1, 2000
SEPULVEDA, Calif. -- A loss of brain cells that make a chemical called "hypocretin" may be responsible for narcolepsy, a debilitating, lifelong disease that causes patients to fall asleep uncontrollably during the day, according to a Department of Veterans Affairs (VA) study published in the September issue of the journal Neuron.
The study, led by Jerome Siegel, Ph.D., a neurobiology researcher at the VA Medical Center in Sepulveda, Calif., and professor of psychiatry at UCLA, found that narcoleptics’ brains had up to 95 percent fewer hypocretin neurons than found in normal brains. These neurons, or nerve cells, are located in the hypothalamus and synthesize the neurotransmitter hypocretin. Scientists have linked hypocretin to narcolepsy in animals, but the cause of human narcolepsy remained unclear.
"This is the first picture we have of what’s wrong in the brains of people with narcolepsy," says Dr. Siegel, who has studied sleep disorders for VA for more than 10 years.
Researchers at Stanford University published findings last year linking a mutation in a hypocretin brain receptor in dogs with narcolepsy. Further research by the team found low levels of hypocretin in human narcoleptics. At the same time, researchers at the University of Texas, while studying appetite in mice, serendipitously found that mice lacking this same chemical developed narcolepsy.
Taken together, the findings showed a strong link between hypocretin and narcolepsy, at least in dogs and mice. In these studies, it appeared that glitches in the chemical signaling system -- specifically, the production and transmission of hypocretin throughout the brain -- caused narcolepsy.
Dr. Siegel’s work suggests a related, but different, cause for human narcolepsy. "There was no cell loss in the animals. But mutations caused the system to work improperly," notes Dr. Siegel. "In humans, however, it appears the cells that synthesize hypocretin are missing altogether."
In the this study, funded by VA’s Medical Research Service and the National Institute of Neurological Disorders and Stroke, Dr. Siegel’s team analyzed 16 human brains from cadavers: 12 were from normal adults, and four from people whose medical records revealed a diagnosis of narcolepsy. The narcoleptic brains had from 85 to 95 percent fewer hypocretin neurons.
At the same time, melanin-concentrating hormone neurons, which are intermingled with hypocretin cells in the brain, were present in normal numbers. This discounts the theory that narcoleptics suffer from a generalized loss of cells in the hypothalamus. Rather, it suggests a targeted degeneration or destruction of hypocretin cells alone. Dr. Siegel believes the loss of hypocretin neurons may stem from an autoimmune attack by the body, or a sensitivity of the cells to certain environmental or biological toxins.
Narcolepsy affects about one in every 2,000 Americans. Patients are excessively drowsy during the day. They fight the urge to sink into a deep sleep while at work, walking around, or even behind the wheel of a car. At night, their sleep is frequently interrupted. Other symptoms include cataplexy -- loss of muscle tone, where patients can suddenly lose consciousness and fall down -- and hypnagogic hallucinations, vivid and dreamlike hallucinations that occur immediately before or after sleep.
While scientists have identified a gene common to almost all narcoleptics, 30 percent of the general population have the same gene. So the gene is only a risk factor, not a cause. Narcolepsy usually develops gradually over several years, with clear symptoms noticeable by early adulthood. Current treatments focus on the use of amphetamines and other stimulant drugs to keep narcoleptics awake during the day. These treatments do not completely reverse symptoms, and usually produce unwanted side effects.
Dr. Siegel’s work confirms the potential for new therapies aimed at restoring the hypocretin messaging system in the brain.
Collaborating with Dr. Siegel on the study were Thomas Thannickal, Ph.D., Robert Nienhuis, Lalini Ramanathan, Ph.D., and S. Gulyani, Ph.D., of UCLA and the Greater Los Angeles VA Healthcare System; Robert Y. Moore, M.D., of the University of Pittsburgh; the late Michael Aldrich, M.D., of the University of Michigan Medical Center, and Marsha Cornford, M.D., of Harbor-UCLA Medical Center.
###
SPECIAL NOTE FOR REPORTERS: Dr. Jerry Siegel of the Sepulveda division for the VA Greater Los Angeles Healthcare System is available for press interviews to discuss this new research. Please contact Beverly Fitzgerald at (310) 268-3340 or beverly.fitzgerald@med.va.gov.
|
