Until quite recently, it was generally believed that each individual is born with a fixed number of nerve cells in the brain, and that these cells gradually degenerate and die during the person's lifetime and cannot be replaced. This theory was disproved when researchers discovered that certain regions of the adult brain do in fact retain their ability to support and promote cell renewal (neurogenesis) throughout life, especially under conditions of mental stimuli and physical activity. One such brain region is the hippocampus, which subserves certain memory functions. But how the body delivers the message instructing the brain to step up its formation of new cells is yet unknown.
The central nervous system (CNS), comprising the brain and spinal cord, has been considered for a long time as "a forbidden city", in which the immune system is denied entry as its activity is perceived as a possible threat to the complex and dynamic nerve cell networks. Furthermore, immune cells that recognize the brain's own components("autoimmune" cells) are viewed as a real danger as they can induce autoimmune diseases. Thus, although autoimmune cells are often detected in the healthy individual, their presence there was perceived as an outcome of the body's failure to eliminate them. But Schwartz's group showed that these autoimmune cells have the potential ability – if their levels are controlled – to fight off debilitating degenerative conditions that can afflict the CNS, such as Alzheimer's and Parkinson's diseases, glaucoma, amyotrophic lateral sclerosis (ALS), and the nerve degeneration that results from trauma or stroke.
In their earlier research, Schwartz and her team provided evidence to suggest that T cells directed against CNS components do not attack the brain but instead, recruit the help of the brain's own resident immune cells to safely fight off any outflow of toxic substances from damaged nerve tissues.
In the present study, the scientists showed that the same immune cells may also be key players in the body's maintenance of the normal healthy brain. Their findings led them to suspect that the primary role of the immune system's T cells (which recognize brain proteins) is to enable the "neurogenic" brain regions (such as the hippocampus) to form new nerve cells, and maintaining the individual's cognitive capacity. The research team led by Prof. Schwartz, included graduate students Yaniv Ziv, Noga Ron and Oleg Butovsky, and in collaboration with former graduate student Dr. Jonathan Kipnis and with Dr. Hagit Cohen of the Ben-Gurion University of the Negev, Beer Sheva.
It was reported before that rats kept in an environment rich with mental stimulations and opportunities for physical activity exhibit increased formation of new nerve cells in the hippocampus. In the present work, the scientists showed for the first time that formation of these new nerve cells following environmental enrichment is linked to local immune activity. To find out whether T cells play a role in this process they repeated the experiment using mice with severe combined immune deficiency (scid mice), which lack T cells and other important immune cells. Significantly fewer new cells were formed in those mice. On repeating the same experiment, this time with mice possessing all of the important immune cells except for T cells, they again found impairment of brain-cell renewal, confirming that the missing T cells were an essential requirement for neurogenesis. They observed that the specific T cells that are helping the formation of new neurons are the ones recognizing CNS proteins.
To substantiate their observations, the scientists injected T cells into immune-deficient mice with the objective of replenishing their immune systems. The results: cell renewal in the injected mice was partially restored – a finding that supported their theory.
In another set of experiments, they found that mice possessing the relevant CNS-specific T cells performed better in some memory tasks than mice lacking CNS-specific T cells. Based on these findings, the scientists suggest that the presence of CNS-specific T cells in mice plays a role in maintaining learning and memory abilities in adulthood.
Schwartz points out that the role of the autoimmune T cells is not to affect the level of intelligence or motivation, but rather, to allow the organism to achieve the full potential of its brainpower. "These findings," she says, "give a new meaning to 'a healthy mind in a healthy body'. They show that we rely on our immune system to maintain brain functionality, and so they open up exciting new prospects for the treatment of cognitive loss." Knowledge that the immune system contributes to nerve cell renewal has potential far-reaching implications for elderly populations, because aging is known to be associated with a decrease in immune system function. It is also accompanied by a decrease in new brain cell formation, as well as in memory skills. Therefore, by manipulating and boosting the immune system, it might be possible to prevent or at least slow down age-related loss of memory and learning abilities.
Prof. Michal Schwartz's research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; the Alan T. Brown Foundation to Cure Paralysis; the Carl and Micaela Einhorn-Dominic Institute for Brain Research; Mr. and Mrs. Irwin Green, Boca Raton, FL; and Mr. and Mrs. Richard D. Siegal, New York, NY.
Prof. Schwartz is the incumbent of the Maurice and Ilse Katz Professorial Chair of Neuroimmunolgy.
The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,500 scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.
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