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Dopamine Drug Leads to New Neurons
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PostPosted: Fri Jul 14, 2006 1:06 am    Post subject: Dopamine Drug Leads to New Neurons Reply with quote

Dopamine Drug Leads to New Neurons and Recovery of Function in Rat
of Parkinson's Disease

U.S. Department of Health and Human Services
NIH News
National Institute of Neurological Disorders and Stroke (NINDS)


EMBARGOED FOR RELEASE: Tuesday, July 4, 2006; 5:00 p.m. ET

CONTACT: Natalie Frazin (fraz...@ninds.nih.gov) or Paul Girolami
(girol...@ninds.nih.gov), 301-496-5924


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

The study suggests that drugs which 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
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
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 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
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
body. 7-OH-DPAT is not used in humans, but its effects on dopamine
receptors are similar to the drugs pramipexole and ropinirole, which
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,
researchers found. Many of the newly generated cells appeared to
into mature neurons, and approximately 28 percent of them appeared to
dopamine neurons by 8 weeks after treatment. Animals treated for 8
also developed almost 75 percent of the normal number of neuronal
connections with other parts of the brain and showed an approximately
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
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.

The NINDS is a component of the National Institutes of Health (NIH)
within the Department of Health and Human Services and is the nation's
primary supporter of biomedical research on the brain and nervous
system. The NINDS mission is to reduce the burden of neurological
disease. Go to


for more information.

The National Institutes of Health (NIH) -- "The Nation's Medical
Research Agency" -- includes 27 Institutes and Centers and is a
component of the U.S. Department of Health and Human Services. It is
primary federal agency for conducting and supporting basic, clinical
translational medical research, and it investigates the causes,
treatments, and cures for both common and rare diseases. For more
information about NIH and its programs, visit




* Van Kampen JM and Eckman CB. "Dopamine D3 Receptor Agonist Delivery
a Model of Parkinson's Disease Restores the Nigrostriatal Pathway and
Improves Locomotor Behavior." "The Journal of Neuroscience", July 5,
2006, Vol. 26, No. 27, pp. 7272-7280.


This NIH News Release is available online at:

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