Immune cells help maintain brain cell renewal
By JUDY SIEGEL-ITZKOVICH original source

A way to slow or delay mental decline may eventually be possible with new findings from a Weizmann Institute of Science team who found that immune cells contribute to maintaining brain health throughout life. The team, headed by Prof. Michal Schwartz of the Rehovot institute's neurobiology department, said that these cells can maintain cognitive ability and brain cell renewal. They published their study Monday in the February issue of Nature Neuroscience.

Knowledge that the immune system contributes to nerve cell renewal has potentially 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.

Schwartz points out that the role of the immune-system T cells is not to affect the level of intelligence or motivation, but rather to allow an 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."

Until quite recently, it was thought that humans are born with a fixed number of nerve cells in the brain and that these cells gradually and inevitably degenerate and die as one's life goes on. It was believed that nerve cells in the brain 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 is responsible for certain memory functions. But how the command to conduct neurogenesis is initiated is as yet unknown.

The central nervous system (CNS), comprising the brain and spinal cord, has been considered for many years "a forbidden city" in which the immune system is denied entry, as the immune system's activity is perceived as a possible threat to the complex and dynamic nerve cell networks. In addition, immune cells that recognize the brain's own components (autoimmune cells) are viewed as a real danger, as they can induce autoimmune diseases - diseases in which the body attacks its own cells. 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, which included graduate students Yaniv Ziv, Noga Ron and Oleg Butovsky, former graduate student Dr. Jonathan Kipnis and Dr. Hagit Cohen of Ben-Gurion University, 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, better known as Lou Gehrig's disease) and nerve degeneration that results from trauma or stroke.

In their earlier research, Schwartz and her team showed that T cells that target CNS components do not attack the brain but 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 new study, they showed that the same immune cells may also be key players in the body's maintenance of a normal, healthy brain. Their findings led them to suspect that the primary role of the T cells, which recognize brain proteins, is to enable the "neurogenic" brain regions to form new nerve cells and maintain the individual's cognitive capacity.

It was previously reported that rats raised in an environment rich with mental stimulation and opportunities for physical activity exhibit increased formation of new nerve cells in the hippocampus. In the present work, 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 help the formation of new neurons were the ones recognizing CNS proteins. To back up their observations, the scientists injected T cells into immune-deficient mice to replenish their immune systems. The result was that cell renewal in the injected mice was partially restored - a finding that supported their theory.