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Immune System May Protect Against Cognitive Disorders

Researchers say mouse study could lead one day to preventive vaccine

MONDAY, May 3, 2004 (HealthDayNews) -- Israeli researchers believe they have demonstrated a link between immune system functioning and cognitive impairment, at least in mice.

While some scientists find the research promising, others point out that applying the findings to human ailments -- such as Alzheimer's disease or schizophrenia -- requires an extraordinary leap.

"It's an extremely exciting study, but it's in mice, so we've got to be very careful how we translate those conclusions to humans," said Dr. Marc Siegel, clinical associate professor of medicine at New York University School of Medicine.

"It's one thing to look at a mouse brain and make comparisons about more primitive emotions, but something like schizophrenia involves cognitive function, and that's very tricky. We have to be cautious about transferring the conclusion about this preliminary data in mice to humans with severe psychiatric illness."

Dr. David Knopman, a neurologist at the Mayo Clinic in Rochester, Minn., was also careful not to take the conclusions too far. "I think that this work in mice linking the immune system to behavior is very interesting and may have implications in the future for human disease," he said. "But the astonishing leap on the part of the authors to state that these findings point to critical factors likely to contribute to age and AIDS-related dementias is far too speculative."

According to the Israeli researchers, some mental disorders have clear physiological characteristics. Schizophrenia, for instance, involves a loss of neurons in the hippocampal area of the brain and also a reduction in the size of the hippocampus.

"There is some speculation afoot that the immune system might be involved in keeping the neurons of the brain in shape to handle high-level stress," Siegel said. "It's metaphoric. If you want to keep your car running at high speed, you better make sure every part is working. There's a theory that the immune system is involved in keeping nerves from degenerating under periods of high stress."

The study authors, who published their findings in the May 3-7 issue of the Proceedings of the National Academy of Sciences, conducted a series of experiments involving mice that had been genetically engineered to have drastic immune deficiencies. The immune-deficient mice were found to have more cognitive problems compared to normal mice.

The researchers then injected the genetically engineered mice with T cells -- key components of the immune system -- to see if the cognitive deficiencies improved. They did -- as evidenced on certain learning tests, such as a water maze.

As the authors state, "The results. . . by suggesting that peripheral T cell deficit can lead to cognitive and behavioral impairment, highlight the importance of properly functioning adaptive immunity in the maintenance of mental activity and in coping with conditions leading to cognitive deficits. These findings point to critical factors likely to contribute to age- and AIDS-related dementias and might herald the development of a therapeutic vaccination for fighting off cognitive dysfunction and psychiatric conditions."

It's this last statement that has some outside experts, such as Knopman, worried. Mice, it has been demonstrated time and again, are not humans. So to extrapolate research findings based on rodents to humans can be tricky, if not impossible.

Nevertheless, Siegel added, the research does indicate "a direction for further research looking at neurodegenerative and psychiatric illness to see whether modulating the immune system helps to treat the condition."

More information

For more on Alzheimer's disease, an age-related dementia, visit the Alzheimer's Disease Education and Referral Center. For more on schizophrenia, check with the National Institute of Mental Health.

SOURCES: David Knopman, M.D., neurologist, Mayo Clinic, Rochester, Minn.; Marc Siegel, M.D., clinical associate professor of medicine, New York University School of Medicine, New York City; May 3-7, 2004, Proceedings of the National Academy of Sciences
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