A vaccination for slowing the brain’s aging process is the goal of Prof. Michal Schwartz of the Weizmann Institute of Science’s Neurobiology Department. “At face value, it sounds like an impossible mission,” she says.
However, her research suggests that the immune system plays a critical role in maintaining a healthy brain and the renewal of brain cells. Consequently, boosting the immune system via a vaccination may one day help to prevent aging of the brain and perhaps slow down disease progression in the cases of Alzheimer’s and Parkinson’s.
The brain is made up of a network of neurons that “talk” to each other via synapses — specialized junctions that act like electric wires, explains Prof. Schwartz. Originally, scientists widely accepted that no new nerves are formed after the birth of an individual.
However, over the last few decades, researchers have found that certain brain regions are able to renew their neurons throughout life, including the olfactory region, spinal cord, eyes, and a certain region in the adult brain — the hippocampus — believed to be the area responsible for our cognitive ability, learning, and memory functions.
“The mechanisms which allow the formation of these new neurons in the adult brain are not fully understood,” says Prof. Schwartz. “Research is still in its infancy.”
However, about ten years ago, Prof. Schwartz and her colleagues found evidence to support their suggestion that cells normally involved in immune responses can promote the healing of damaged neurons in the central nervous system (CNS). Prior to that time, the scientific community thought immune cells should be kept away from the brain, because they were perceived as a threat to the organ’s delicate networks. “Our discovery therefore ran against the dogma,” she said.
The researchers asked themselves what kind of immune cells are needed to generate this healing and found that the answer seemed to be T cells (a type of white blood cell produced in the bone marrow and which are part of the body’s immune defense system) that recognize self-proteins in the brain.
Originally, researchers hypothesized that the thymus deletes all T cells that recognize the body’s own proteins, as they could ultimately cause autoimmune disease. Over the years, however, scientists have found the presence of autoimmune cells in healthy individuals and the debate has been whether they are an outcome of a failure of deletion or a purposeful selection.
Prof. Schwartz and her colleagues suggest that, based on their evidence, autoimmune cells are needed in everyday life to fight off enemies arising within the body, such as toxic substances generated by damaged nerve tissues. But the level of these autoimmune cells must be controlled; if they are not, they can cause autoimmune disease, she explains.
Prof. Schwartz and her colleagues first observed the presence of autoimmune cells in the CNS of animals recovering from optic nerve injury in the 1990s. Shortly thereafter, they found that animals receiving a vaccination of T cells experienced a better recovery from spinal cord injury than animals that did not receive vaccinations.
In their latest research, published in Nature Neuroscience, Prof. Schwartz and her colleagues showed that these autoimmune T cells may also be key players in the body’s maintenance of a normal, healthy brain, enabling the brain regions to form new nerve cells, maintaining the person’s cognitive capacity.
They already knew from earlier research conducted by other groups that rats kept in an enriched environment with mental stimulation, socialization, opportunities for physical activity, and proper nourishment, exhibited increased formation of new neurons close to the hippocampus region, when immune cells were present in the brain.
Therefore, to test their theory, Schwartz and colleagues repeated the experiment using genetically engineered mice that lacked T cells. Significantly fewer neurons were formed in those mice, even though they lived in an enriched environment.
They then used engineered mice possessing all of the other important immune cells except for the T cells that recognize brain-specific antigens. They found impairment of brain-cell renewal, confirming that the missing T cells appear to be an essential requirement for this process, and can be partially restored by replenishment of the immune-cell pool.
In another set of experiments, the researchers found that mice possessing the relevant CNS-specific T cells performed better in some memory tasks than mice lacking CNS-specific T cells, suggesting that the presence of these T cells in mice plays a role in maintaining learning and memory abilities in adulthood.
Based in part on this research, Prof. Schwartz speculates that as people age and the effectiveness of their immune systems declines, safely boosting autoimmunity via a vaccine using a weak self-antigen may be a way to preserve neurogenesis.
In animal models, this approach is already being tested for the neurodegenerative diseases Alzheimer’s, Parkinson’s, and glaucoma. It may help boost a weak autoimmune response to these diseases and slow down chronic neurodegeneration, explains Prof. Schwartz. Such a vaccine may be used in combination with stem cell therapy to create a synergistic effect, she added.
Prof. Schwartz anticipates that this research will lead to many different ways to prevent brain senescence, development of dementia, and halt the progress of neurodegenerative diseases. “The bottom line is that we all hope that this research will translate into a healthy brain and a healthy immune system,” she says.
Prof. Michal Schwartz's research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; the Carl and Micaela Einhorn-Dominic Brain Research Institute; the Julius and Ray Charlestein Foundation; the Mario Negri Institute for Pharmacological Research – Weizmann Institute of Science Exchange Program; 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 Neuroimmunology.The Weizmann Institute of Science in Rehovot, Israel, is one of the world's foremost centers of scientific research and graduate study. The American Committee for the Weizmann Institute of Science is a community of dedicated people who share a common vision in support of the Institute. The generous assistance the Institute receives from individuals, foundations, and corporations is vital for its future. Committee members show their devotion to the advancement of the Institute's goals by becoming partners in the search for answers to the most difficult challenges facing humanity.
