Science + Technology

UCLA Researchers Discover Link Between Parkinson’s and Narcolepsy

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Parkinson's disease is well-known for its progression of motor disorders:stiffness, slowness, tremors, difficulties walking and talking. Less well knownis that Parkinson's shares other symptoms with narcolepsy, a sleep disordercharacterized by sudden and uncontrollable episodes of deep sleep, severefatigue and general sleep disorder.

Now a team of UCLA and Veterans Affairs researchers think theyknow why — the two disorders share something in common: Parkinson's diseasepatients have severe damage to the same small group of neurons whose losscauses narcolepsy. The findings suggest a different clinical course oftreatment for people suffering with Parkinson's that may ameliorate their sleepsymptoms.

In their report (currently online) in the June issue of thejournal Brain, Jerry Siegel, professor of psychiatry and biobehavioral sciencesat the Semel Institute for Neuroscience and Human Behavior at UCLA, assistantresident neurobiologist Thomas C. Thannickal and associate researchphysiologist Yuan-Yang Lai have determined that Parkinson's disease patientshave a loss of up to 60 percent of brain cells containing the peptidehypocretin. In 2000, this same group of UCLA researchers first identified thecause of narcolepsy as a loss of hypocretin, thought to be important inregulating the sleep cycle. This latest research points to a common cause forthe sleep disorders associated with these two diseases and suggests thattreatment of Parkinson's disease patients with hypocretin or hypocretin analogsmay reverse these symptoms.

More than 1 million people in the U.S. have been diagnosed withParkinson's disease, and approximately 20 million worldwide. (The percentage ofthose afflicted increases with age.) Narcolepsyaffects approximately one in 2,000 individuals — about 150,000 in the United Statesand 3 million worldwide. Its main symptoms are sleep attacks, nighttimesleeplessness and cataplexy, the sudden loss of skeletal muscle tone withoutloss of consciousness; that is, although the person cannot talk or move, theyare otherwise in a state of high alertness, feeling, hearing and rememberingeverything that is going on around them.

"When we think of Parkinson's, the first thing that comes to mindare the motor disorders associated with it," said Siegel, who is also chief ofneurobiology research at the Sepulveda Veterans Affairs Medical Center inMission Hills, Calif. "But sleep disruption is a major problem in Parkinson's,often more disturbing than its motor symptoms. And most Parkinson's patients havedaytime sleep attacks that resemble narcoleptic sleep attacks."

In fact, said Siegel, Parkinson's disease is often preceded andaccompanied by daytime sleep attacks, nocturnal insomnia, REM sleep disorder,hallucinations and depression. All of these symptoms are also present innarcolepsy.

In the study, the researchers examined 16 human brains fromcadavers — five from normal adults and 11 in various stages of Parkinson's — andfound an increasing loss of hypocretin cells (Hcrt) with disease progression.In fact, said Siegel, the later stages of Parkinson's were "characterized by amassive loss of the Hcrt neurons. That leads us to believe the loss of Hcrtcells may be a cause of the narcolepsy-like symptoms of [Parkinson's] and maybe ameliorated by treatments aimed at reversing the Hcrt deficit."

Funding for the study was provided by the National Institutes ofHealth and the Medical Research Service of the U.S. Department of VeteransAffairs.

The SemelInstitute for Neuroscience and Human Behavior at UCLA is an interdisciplinaryresearch and education institute devoted to the understanding of complex humanbehavior, including the genetic, biological, behavioral and socioculturalunderpinnings of normal behavior and the causes and consequences of neuropsychiatricdisorders. In addition to conducting fundamental research, the institutefaculty seeks to develop effective treatments for neurological and psychiatricdisorders, improve access to mental health services, and shape national healthpolicy regarding neuropsychiatric disorders.

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