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Evidence Links Cocaine Abuse And Parkinson's Disease

Date:
December 14, 2005
Source:
St. Jude Children's Research Hospital
Summary:
Adults who abuse cocaine might increase their risk of developing Parkinson's disease (PD), and pregnant women who abuse cocaine could increase the risk of their children developing PD later in life, according to results of laboratory studies performed by investigators at St. Jude Children's Research Hospital.

Adults who abuse cocaine might increase their risk of developing Parkinson's disease (PD), and pregnant women who abuse cocaine could increase the risk of their children developing PD later in life, according to results of laboratory studies performed by investigators at St. Jude Children's Research Hospital.

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The study's findings are important because there are currently more than 2 million cocaine abusers in the US today, the researchers said. Many individuals who abused the drug during the height of the cocaine abuse epidemic of the 1970s and 1980s are now entering their older years, when symptoms of PD are likely to emerge.

A report on this work appears in the online, prepublication edition of Neuroscience.

The St. Jude team showed in laboratory models of both the adult and fetal brains that exposure to cocaine alters the nerve bodies in the region of the brain called the substantia nigra. This damage made the neurons more susceptible to MPTP, a toxin known to cause symptoms of PD.

The nigrostriatal system is a pathway of nerves that originates in the area called the substantial nigra pars compacta (SNpc) and spreads out into certain other parts of the brain. The neurons in the SNpc make the neurotransmitter dopamine, and degeneration of this area and the nigrostriatal system is one of the major hallmarks of PD, according to Richard Smeyne, Ph.D., an associate member of the St. Jude Department of Developmental Neurobiology.

"Our findings suggest that cocaine makes the SNpc in adults susceptible to further damage from environmental toxins that can cause Parkinson's disease," Smeyne said "The findings also strongly suggest that women who abuse cocaine during pregnancies put their children at an increased risk for developing Parkinson's disease."

Cocaine is also known to disrupt the normal function of the dopamine transporter, a protein that sweeps up dopamine from the synapse after it stimulates its target nerve, he added. Disruption of this process causes an abnormal rise in the concentration of dopamine in the synapse. This poses a threat to the brain because dopamine can interact with other chemicals to become a free radical--a highly reactive molecule that can damage tissue. "So the increase in the amount of dopamine in the synapse can lead to high levels of destructive free radicals that damage this area of the brain," Smeyne said.

The St. Jude team studied the effect of cocaine in laboratory models that are resistant to a toxin called MPTP, which is known to cause PD-like damage in the brain. The investigators used this model to determine if cocaine altered the nigrostriatal system so it became sensitive to MPTP.

Exposure to cocaine did not affect the number of cells in the SNpc of adult and fetal models but did make them more susceptible to damage from MPTP, the researchers reported. Furthermore, in both the adult and fetal models, cocaine exposure disrupted the balance between the proteins that sweep up dopamine from the synapses and bring them into the pre-synaptic cell and the sacs that sequester (package) them in those neurons. Specifically, the ratio of transporter proteins to the sacs increased by 27 percent in the fetal models and by 28 percent in adult models, the investigators reported.

"This means that the transporter proteins were pumping more dopamine back into the pre-synaptic nerves than could be repackaged in those sacs," Smeyne explained. "And that was allowing dopamine to accumulate freely inside the cell, where it can produce free radicals. That kind of stress can make the nerve susceptible to other environmental toxins. Smeyne theorizes that toxins that enter the body could then cause damage in the substantia nigra that leads to Parkinson's disease.

The study also found that cocaine exposure decreased the number of certain dopamine receptors called D2 autoreceptors. These autoreceptors control the production and/or release of dopamine; when they are in short supply, the level of dopamine in the synapse rises. This in turn leaves the synapse (connection between nerves) vulnerable to free radical damage, according to Smeyne.

"Based on these findings it might not be surprising to see a rise in the number of cases of Parkinson's disease in the next 10 or 20 years or so," said Steven A. Lloyd, Ph.D. the first author of the article. Lloyd was a graduate student in Smeyne's laboratory during this work and is now an assistant professor of psychology at Rhodes College in Memphis.

Smeyne's team previously published their findings that exercise confers protection on mice that otherwise would have developed PD following treatment with MPTP; and that the rise in the level of GDNF appeared to be key to that protection. The article appeared in the special October 2004 issue of Molecular Brain Research called "Molecular Aspects of Parkinson's Disease."

###

The other author of the current article is C. J. Faherty, Ph.D. This work was supported in part by ALSAC.

St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fund-raising organization. For more information, please visit www.stjude.org.


Story Source:

The above story is based on materials provided by St. Jude Children's Research Hospital. Note: Materials may be edited for content and length.


Cite This Page:

St. Jude Children's Research Hospital. "Evidence Links Cocaine Abuse And Parkinson's Disease." ScienceDaily. ScienceDaily, 14 December 2005. <www.sciencedaily.com/releases/2005/12/051214084800.htm>.
St. Jude Children's Research Hospital. (2005, December 14). Evidence Links Cocaine Abuse And Parkinson's Disease. ScienceDaily. Retrieved October 24, 2014 from www.sciencedaily.com/releases/2005/12/051214084800.htm
St. Jude Children's Research Hospital. "Evidence Links Cocaine Abuse And Parkinson's Disease." ScienceDaily. www.sciencedaily.com/releases/2005/12/051214084800.htm (accessed October 24, 2014).

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