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Dopamine drug leads to new neurons and recovery of function in rat model of Parkinson's

not develop new neurons, recent studies have shown that the brain contains stem cells and that new neurons can develop in some regions. Studies by Dr. Van Kampen and others also have shown that drugs which affect dopamine D3 receptors can trigger development of new neurons (a process called neurogenesis) in the brains of adult rats. Until now, however, no one had shown that the newly developed neurons could connect with other parts of the brain and restore function.

"This is the first study to show that endogenous neurogenesis [development of new neurons from cells already in the brain] can lead to recovery of function in an animal model of Parkinson's disease," says Dr. Eckman.

The researchers gave either 2-, 4-, or 8-week continuous infusions of a drug called 7-OH-DPAT, which increases the activity of dopamine D3 receptors, into the brain ventricles of adult rats with neuron loss in the substantia nigra and symptoms similar to human PD on one side of the body. 7-OH-DPAT is not used in humans, but its effects on dopamine receptors are similar to the drugs pramipexole and ropinirole, which are approved to treat PD. The rats also received injections of a chemical called bromodeoxyuridine (BrdU), which marks proliferating cells, and infusions of a substance that fluorescently "traces" how neurons connect. The animals were tested before and 3 days after receiving the treatment to see how well they could walk and reach to retrieve food pellets with their paws. A subset of the rats was tested again 2 and 4 months following the treatment.

Rats treated with 7-OH-DPAT had more than twice as many proliferating cells in the substantia nigra as rats that were treated with saline, the researchers found. Many of the newly generated cells appeared to develop into mature neurons, and approximately 28 percent of them appeared to be dopamine neurons by 8 weeks after treatment. Animals treated for 8 weeks also developed almost 7
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Contact: Natalie Frazin
301-496-5924
NIH/National Institute of Neurological Disorders and Stroke
4-Jul-2006


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