Unlikely Brain Boosters

Healthy body - healthy mind” is one of those sayings often quoted to children who resist vegetables or bedtime. But there may be more truth to the saying than your parents ever suspected: A new study reveals a surprising connection between the body’s immune system and the brain.

Though the cells of the immune system patrol the entire body, waging daily battle against all sorts of threats, prevailing wisdom has held that the brain remains neutral territory, blockaded against immune cells and invaders alike - any immune cells straying into the demilitarized zone were believed to interfere with the brain’s activity. But a study by Prof. Michal Schwartz and postdoctoral fellow Dr. Jonathan Kipnis of the Neurobiology Department now challenges this widely held viewpoint, shedding new light on the role of the immune system and its part in maintaining healthy brain function. Their study appeared in the Proceedings of the National Academy of Sciences (PNAS), USA.

Schwartz and Kipnis, who were joined by Dr. Hagit Cohen of Ben-Gurion University of the Negev, tested how mice bred for faulty immune systems performed when challenged to find a hidden platform in a pool of water. While normal mice learned to swim the shortest route in a matter of days, the immunity-challenged mice took much longer. But when the missing immune cells were injected into these mice, their learning curves jumped into the normal range.

Having demonstrated a possible role for immune cells in normal brain functioning, the team asked whether the immune system might also hold the key to mental disorders characterized by imbalanced brain activity. They theorized that the supply of immune cells in the brain in such diseases is either insufficient or subject to malfunction. If so, an immune system boost might be enough to overcome the impairment.

For this experiment, the scientists gave normal mice an amphetamine drug that mimics the effects of mental dysfunction in the brain. They then administered the drug Cop-1, which appears to act as a broad vaccine for the whole immune system. The group that did not receive Cop-1 vaccination exhibited disturbed, irrational behavior during the learning test, whereas the vaccinated mice behaved much like normal ones, learning to swim for the platform without any symptoms of mental dysfunction.

“There’s a seemingly logical connection,” says Schwartz. “Age- and AIDS-related dementias, for instance, might be tied to the decline in immune function. Our most important finding is that the brain does not operate independently of the rest of the body’s systems; rather, the immune system plays a pivotal role in its performance.”

Because the study impacts on several areas of higher brain function, including learning, emotions and mental stability, it might have important implications for different fields of neuromedical research. Further studies based on these findings may one day yield vaccines to prevent or treat such diseases as schizophrenia, post-traumatic stress disorder and dementias.

The dopamine tightrope walk

Immunity is a tricky balancing act. Too much, and autoimmune diseases such as diabetes or multiple sclerosis can result. Too little, however, has been shown to be tied to tumor growth and nervous system degeneration. To ensure that the autoimmune T cells will help without hurting, a second set of cells, called regulatory T cells (T-reg), work to keep them in check.

But what regulates the regulators? For some time, scientists have searched for an answer. Schwartz, Kipnis and members of their lab team have now proposed that the key to immune control may lie in the brain. In recently published research, they showed that dopamine - a pivotal chemical messenger more commonly known to be involved in movement, feelings and emotions - provides a direct line of communication to the regulators. It controls T-reg cell activity, ultimately allowing the autoimmune T cells to function upon need without the risk of developing autoimmune disease.

Indeed, research by others has provided tantalizing hints that dopamine imbalances may affect immunity: high dopamine levels have been linked to reduced tumor and neurodegenerative conditions, whereas dopamine deficiency increases the rates of these diseases, while reducing autoimmune pathologies.

Prof. Schwartz’s research is supported by the Nella and Leon Benoziyo Center for Neurosciences; the Alan T. Brown Foundation to Cure Paralysis; the Carl and Micaela Einhorn-Dominic Brain Research Institute; the Glaucoma Research Foundation; the Daniel Heumann Fund for Spinal Cord Research; Mr. and Mrs. Irwin Green, Boca Raton, FL; and Mr. and Mrs. Richard D. Siegal, New York, NY. She is the incumbent of the Maurice and Ilse Katz Professorial Chair of Neuroimmunolgy.