Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Dopamine imbalances cause sleep disorders in animal models of Parkinson's disease and schizophrenia

11.10.2006
Neuroscientists at Duke University Medical Center working with genetically engineered mice have found that the brain chemical dopamine plays a critical role in regulating sleep and brain activity associated with dreaming.

When dopamine levels were dramatically reduced, the mice could no longer sleep, the scientists said. When dopamine levels were increased, the mice exhibited brain activity associated with dreaming during wakefulness.

The same processes likely occur in humans, according to the researchers. They said the findings give insight into the sleep problems common among patients suffering from Parkinson's disease, a neurodegenerative disorder in which brain cells containing dopamine die or become impaired.

"Our study may lead to development of new diagnostic tools for the early detection of Parkinson's disease based on the sleep disturbances that are often associated with motor symptoms of the disease," said senior study investigator Miguel Nicolelis, M.D., Ph.D., Anne W. Deane professor of neuroscience.

The findings may also provide a mechanism to explain some of the symptoms, such as hallucinations, experienced by psychotic and schizophrenic patients, he said.

The researchers published their findings in the Oct. 11, 2006, issue of the Journal of Neuroscience. The work was supported by the National Institutes of Health, the Hereditary Disease Foundation and the Anne W. Deane professorship to Nicolelis.

Parkinson's disease occurs when the brain cells, or neurons, that normally produce dopamine die or become impaired. Once 60 percent to 70 percent of the neurons are knocked out of commission, the jerky movements and fixed facial expressions characteristic of Parkinson's appear.

The new study suggests that destruction of significantly fewer dopamine-producing cells could result in sleep problems long before the motor problems become apparent, the researchers said.

Dopamine is a "neurotransmitter" that carries signals from one neuron to another. It is known to control movement, balance, emotion and the sense of pleasure.

Normally, when a signal needs to travel through the brain, neurons release dopamine to transport the signal across the gap, or synapse, between neurons. A kind of protein pump, called a transporter, recycles dopamine back to the neurons to prepare for the next burst of signal.

In studies 10 years ago, Marc Caron, Ph.D., James B. Duke professor of cell biology and a co-investigator in the current study, used the techniques of genetic engineering to produce a strain of mice that lacked this protein transporter. In such transgenic mice, dopamine lingers outside brain cells, stimulating surrounding neurons hundreds of times longer than normal. Caron and colleagues found that when they placed the mice in an unfamiliar environment, such as a new cage, the animals groomed themselves excessively and ran around the cage, mirroring the bizarre behaviors experienced by people with schizophrenia.

The researchers used this same strain of transgenic mice in the current study. They reasoned that both schizophrenia and Parkinson's disease are characterized by imbalances of dopamine in the brain, and that patients with both diseases experience sleep disturbances. So the researchers sought to further manipulate the mice to study the role of dopamine in the sleep cycle.

First, the researchers treated the mice with a chemical that stops the production of dopamine entirely. In fairly short order, the mice had used up their initial supply of dopamine and were running on empty.

The mice became rigid, immobile, and unable to sleep or dream, displaying symptoms similar to those experienced by patients with Parkinson's disease, the researchers said.

The researchers then measured the electrical activity in each animal's hippocampus, the region of the brain known to be involved in emotion and memory, during three major brain states: wakefulness, quiet sleep and dreaming (also known as rapid eye movement sleep). Using electrodes finer than a human hair implanted into individual neurons, the researchers could monitor signals passed among hundreds of neurons in the treated mice. They found a lack of dopamine completely suppressed brain activity and behaviors associated with quiet sleep and dreaming.

To verify that the sleep disturbances were caused by a lack of dopamine, the researchers gave the mice L-dopa, a drug used to increase the levels of dopamine in Parkinson's disease patients. The treated animals regained the brain patterns and behaviors associated with sleep and dreaming, demonstrating the critical role dopamine plays in the sleep-wake cycle, according to the researchers. Further pharmacological testing revealed that L-dopa exerted its effects by docking at a specific site, called the D2 receptor, on the surface of the neurons.

"Sleep disorders may be the first sign of Parkinson's disease," said lead study investigator Kafui Dzirasa, an M.D.-Ph.D. student working in Nicolelis's laboratory.

"By further studying the sleep patterns in animal models of Parkinson's disease, we hope to come up with a sleep diagnosis test that could detect the early signs of the disease years before the major symptoms appear," he said.

The study also provided insights into the biology underlying schizophrenia, the researchers said. They found that the excess dopamine in the brains of the mice generated patterns of brain activity that made it look as though the animals were experiencing brain activity associated with dreaming when they were actually awake.

"One of the preeminent ideas of classical psychiatry is that people who had hallucinations, such as schizophrenics, were actually dreaming while they are awake," Nicolelis said. "Our results give some initial biological evidence for this theory."

Marla Vacek Broadfoot | EurekAlert!
Further information:
http://www.duke.edu

Further reports about: Animal Disease Parkinson' dopamine dreaming patients schizophrenia symptoms

More articles from Life Sciences:

nachricht Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo

nachricht Research reveals how order first appears in liquid crystals
23.05.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Research reveals how order first appears in liquid crystals

23.05.2018 | Life Sciences

Space-like gravity weakens biochemical signals in muscle formation

23.05.2018 | Life Sciences

NIST puts the optical microscope under the microscope to achieve atomic accuracy

23.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>