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

In preliminary results, researchers have shown that a drug which mimics the effects of the nerve-signaling chemical dopamine causes new neurons to develop in the part of the brain where cells are lost in Parkinson's disease (PD). The drug also led to long-lasting recovery of function in an animal model of PD. The findings may lead to new ways of treating PD and other neurodegenerative diseases. The study was funded in part by the NIH's National Institute of Neurological Disorders and Stroke (NINDS).

The study suggests that drugs that affect dopamine D3 receptors might trigger new neurons to grow in humans with the disease. Some of these drugs are commonly used to treat PD. The finding also suggests a way to develop new treatments for PD. The results appear in the July 5, 2006, issue of The Journal of Neuroscience.

Parkinson's disease, a progressive neurodegenerative disorder that causes tremors, stiffness, slow movements, and impaired balance and coordination, results from the loss of dopamine-producing neurons in part of the brain called the substantia nigra. While many drugs are available to treat these symptoms during the early stages of the disease, the treatments become less effective with time. There are no treatments proven to slow or halt the course of PD. However, many researchers have been trying to find ways of replacing the lost neurons. One possible way to do this would be to transplant new neurons that are grown from embryonic stem cells or neural progenitor cells. However, this type of treatment is very difficult for technical reasons.

The new study, conducted by Christopher Eckman, Ph.D., and Jackalina Van Kampen, Ph.D., at the Mayo Clinic College of Medicine in Jacksonville, Florida, focused on a second possible way to restore function ?prompting stem cells that normally remain dormant in the adult brain to develop into neurons. While most researchers previously believed the adult brain could not develop new neuron s, 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 75 percent of the normal number of neuronal connections with other parts of the brain and showed an approximately 80 percent improvement in their movements and a significantly improved ability to retrieve food pellets. These effects lasted for at least 4 months after the treatment ended.

"There was a profound behavioral effect of the treatment, even after it 'washed out' of the system," Dr. Eckman notes. "This shows that the treatment affects the underlying pathology."

Several previous studies point to the possibility that drugs like pramipexole and ropinirole might modify the course of PD, but this effect is difficult to test and has never been proven, says Dr. Eckman. While these drugs are useful in treating the symptoms of PD, they have not been designed to prompt development of new neurons, he adds. Altering how the current drugs work or developing new compounds to enhance neurogenesis could provide an entirely new avenue for treating this disease.

"These findings are very exciting for several reasons. Being able to stimulate endogenous stem cells in patients would alleviate the need for transplantation of engineered cells, and as a drug therapy, it would be also easy to administer to patients. Moreover, given that similar drugs exist, medicinal chemistry to maximize this effect could be achieved quickly," says Diane Murphy, Ph.D., the NINDS program director for the grant that funded this research.

Dr. Eckman and Dr. Van Kampen are now looking at how different doses of pramipexole and similar drugs affect neurogenesis. Once they identify the most effective doses in animals, researchers might be able to test comparable doses in humans. They are also carrying out experiments to learn if using drugs that act on other kinds of receptors might stimulate neurogenesis in Alzheimer's disease and other neurodegenerative diseases.


Source:NIH/National Institute of Neurological Disorders and Stroke

Related biology news :

1. Discovery of New Dopamine Action May Yield Alternative Psychiatric Drugs
2. Dopamine used to prompt nerve tissue to regrow
3. Study of genomic DNA leads to new advances in cancer diagnostics
4. Combination therapy leads to partial recovery from spinal cord injury in rats
5. Chemical guidance of T cells leads to immunologic memory and long-term immunity
6. Basic research leads to a novel cancer therapy
7. Less antibiotic use in food animals leads to less drug resistance in people, study shows
8. MBL leads effort to update E. coli genome
9. With cochlear implants, earlier use leads to better speech
10. Pest control research leads to pain control discovery
11. UT Southwestern researchers find gene mutation that leads to broken hearts
Post Your Comments:

(Date:5/3/2016)... Lithuania , May 3, 2016  Neurotechnology, ... released the MegaMatcher Automated Biometric Identification System ... of large-scale multi-biometric projects. MegaMatcher ABIS can process ... accuracy using any combination of fingerprint, face or ... MegaMatcher SDK and MegaMatcher Accelerator ...
(Date:4/26/2016)... , April 27, 2016 ... "Global Multi-modal Biometrics Market 2016-2020"  report to their ... , The analysts forecast the global ... of 15.49% during the period 2016-2020.  ... of sectors such as the healthcare, BFSI, transportation, ...
(Date:4/14/2016)... April 14, 2016 BioCatch ... Detection, today announced the appointment of Eyal Goldwerger ... role. Goldwerger,s leadership appointment comes at a ... of the deployment of its platform at several of ... technology, which discerns unique cognitive and physiological factors, is ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 2016  The Biodesign Challenge (BDC), a university competition ... harness living systems and biotechnology, announced its winning teams ... New York City . The ... projects at MoMA,s Celeste Bartos Theater during the daylong ... senior curator of architecture and design, and Suzanne ...
(Date:6/23/2016)... ... June 23, 2016 , ... STACS DNA Inc., the sample tracking software company, ... Crime Laboratory, has joined STACS DNA as a Field Application Specialist. , “I ... President and COO of STACS DNA. “In further expanding our capacity as a scientific ...
(Date:6/23/2016)... Calif. , June 23, 2016  Blueprint Bio, ... biological discoveries to the medical community, has closed its ... Matthew Nunez . "We have received ... with the capital we need to meet our current ... essentially provide us the runway to complete validation on ...
(Date:6/23/2016)... ... June 23, 2016 , ... ... at the Pennsylvania Convention Center and will showcase its product’s latest features from ... also be presenting a scientific poster on Disrupting Clinical Trials in The Cloud ...
Breaking Biology Technology: