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publicado em 09/09/2011 às 11h00:00
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Lack of dopamine affects motor skills and may be the cause of Parkinson's disease

Discovery sheds light on the disease and indicate potential therapeutic targets to reverse loss of control of movements

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Foto: Gladstone Institutes
Anatol Kreitzer. researcher involved in the study
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Anatol Kreitzer. researcher involved in the study

In an article published online in Neuron, the researcher Anatol Kreitzer, the Gladstone Institutes, identified as the loss of dopamine alters the wiring of a small group of brain cells, setting off a chain of phenomena that eventually leads to difficulties in controlling movement, a hallmark of Parkinson's disease. More than half a million people suffer from the disease in the U.S. alone, including famous personalities such as boxer Muhammad Ali and actor Michael J. Fox

"The development of truly effective therapies and well tolerated for Parkinson's has been difficult. Kreitzer The discovery sheds new light on the intricate processes that underlie the problem with this disabling condition and hopefully lead to the development of more effective drugs," said professor of neurology and neuroscience Lennart Mucke of the University of California at San Francisco (UCSF), who directs research on neurological diseases of the Gladstone Institutes.

Typically, two types of brain cells called medium spiny neurons (MSNs), work together to coordinate body movements. One type acts as an accelerator and the other as a brake. One hypothesis is that dopamine prevents the reduction of the balance between two opposing forces of MSN, leading to problems with movement. But Kreitzer questioned whether other factors may also be involved. To better understand the relationship between dopamine and MSNs in people with Parkinson's, it artificially removes dopamine from the brain of mice and monitors specific changes in the brains of these animals.

Just as in humans, mice lacking dopamine began to feel the motor symptoms of Parkinson's disease, including tremors, balance problems and slowed movement. But Kreitzer found that decreased levels of dopamine not only keeps the balance between the two types of MSNs, as already known, but also changes the interaction between them and another group of neurons, known FSNs.

Kreitzer's experiments showed that in normal circumstances, FSNs connect to both types of MSNs in a similar manner. But without the dopamine signaling circuits between FSNs and reconnect the neurons begin to target a type of MSN on the other. Kreitzer used computer simulations to show that this small change upsets the uptime of MSN, which is essential for normal movement.

Ultimately, this reconnection can be an important factor in the development of motor problems of Parkinson's. "Our research has revealed how a totally different group of neurons may play a role in the symptoms of Parkinson's disease. We expect to achieve the changes between these neurons directly with drug therapies, to alleviate some of the most debilitating consequences of Parkinson's," said Kreitzer, who is also assistant professor of physiology and neurology at UCSF.

   Palavras-chave:   Dopamine neurons    Brain    Connections    Activity    Movement    Disease    Neurodegenerative disease    Parkinson's    California    USA   
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