Gene-Altered Mouse May Provide New Insights To Schizophrenia by David Israel

DURHAM, N.C. -- Researchers at the Howard Hughes Medical Institute at Duke University are investigating the results of deleting particular genes from a mouseís nervous system. The mutant mice have been given the term "knockout" mice and are providing new insights into how many dopamine related diseases are formed. Schizophrenia is one such disease that researchers are hoping to understand better as a result of looking at "knockout" mice.

Bruno Giros, the chief investigator, along with scientists from Duke, UNC-Chapel Hill, published in the journal Nature that the mechanisms of many addictive drugs, Parkinsonís Disease, Schizophrenia, and several other psychiatric disorders were caused by the brains inability to regulate dopamine. Dopamine is a key neurotransmitter in the brain.

Neurotransmitters such as dopamine, serotonin and adrenaline are chemical messengers that cause other nerve cells to give a signal which in turn gives a message to various parts of the body or brain. When a nerve cell encounters enough neurotransmitter, the charge inside the cell changes with respect to its surroundings causing a signal in the form of an electrical impulse to be sent down the axon of the nerve cell. When the charge reaches the end of the nerve cell it causes the nerve cell to release its own neurotransmitter to another neuron jointed nearby in a joining called a synapse. Too much or too little neurotransmitter release can cause neurons to either fire too often or not enough which can lead to various disorders.

The scientists removed from the mice, a protein necessary for the transport of dopamine. Without this valuable protein, dopamine remained in the synapse too long and flooded the brainís receptors until all the dopamine was received by the brain in a quantity that was too large for the brain to handle. Having too much dopamine like this, appeared to cause the over stimulation characteristic of schizophrenic delusions or cocaine highs.

Regulation of dopamine is critical because it has been known for years that an abundance of dopamine in the limbic system causes these hallucinations while not enough dopamine in the brains emotional center causes depression. Lack of dopamine elsewhere is responsible for Parkinsonís disease as well.

Related Web Links:

Web links: http://www.dukenews.duke.edu/Latest/schizo2 the original article with graphic and http://www.dukenews.duke.edu/Radio/mouse http://www.dukenews.duke.edu/radio/rpage the Duke News Service Internet web site radio page -Caron talks about the original article

http://www.the-scientist.library.upenn.edu/yr1996/mar/looming_960318.html An overview of what's going on in the search for "disease genes" and what a find means towards developing new drugs.


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