~ Findings Support Contribution Of Oxidative Stress To Brain Aging

An article published online on November 27, 2005 in the journal Nature Neuroscience reported that a protein found in mice and humans appears to help protect nerve cells from oxidative stress. Oxidative stress has been associated with neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease and can be reduced by antioxidants such as glutathione. Because the brain uses a large amount of oxygen and contains a relatively high amount of lipids, it is particularly vulnerable to oxidative stress and the damage it can cause.

Chief of neurology and rehabilitation services at San Francisco’s Veteran’s Administration Medical Center, Raymond Swanson, MD and his colleagues at the VA and University of California, San Francisco found that, in mice, excitatory amino acid carrier-1 (EAAC3 in humans), which is expressed by neurons as a glutamate transporter, can also rapidly transport the amino acid cysteine, which is necessary for the synthesis of glutathione within the nerve cells. Dr Swanson has called glutathione the most important brain antioxidant.

Dr Swanson’s team observed that mice bred to lack EAAC1 developed increased brain atrophy and behavioral changes at 11 months compared to normal mice of the same age. Examination of the brains of these mice found reduced neuronal glutathione and increased oxidant levels, as well as ten times the susceptibility to oxidant injury compared to mice that produced EAAC1.

When the mice lacking EAAC1 were given N-acetylcysteine (NAC) five hours before their brains were examined, the glutathione content of the neurons was normalized. By its ability to cross lipid membranes, N-acetylcysteine was able to provide cysteine to cells that lacked cysteine transport, thereby enabling them to synthesize glutathione. Additionally, neurons from mice treated with NAC showed greater oxidant-scavenging capacity compared to untreated mice.

Dr Swanson commented, "It's known that neurons don't take up cysteine directly, and it's never been clear exactly how it gets there. This study provides the first evidence that EAAC1 is the mechanism by which cysteine gets into neurons – and that transporting cysteine is probably its chief function."

Although he finds the concept “appealing,” but difficult to prove or disprove, Dr Swanson stated that the results "support the idea that oxidative stress contributes to aging" in the brain. "This certainly adds credence to the idea," he observed.
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