In your book, you argue that the immune system and the brain are not, as previously thought, completely separate, and that the immune system actually plays a role in keeping the brain healthy. Where did this idea come from?
MS: For a long time, we thought that because of the blood-brain barrier between the brain and the circulatory system, immune cells were excluded from the brain, along with the rest of the central nervous system. And that was partly because at the time, we knew that parts of the central nervous system—including the brain, the spinal cord and the optic nerve—didn't recover from injury. After getting my PhD in immunology and doing postdoctoral work in a neuroscience lab that focused on nerve regeneration, I started to think it was unlikely that such precious tissue couldn't be assisted by the immune system when it was in need. It didn't make any sense.

So you started trying to disprove the old theory?
MS: Yes, and the first breakthrough came in 1998. My research team at the Weizmann Institute of Science and I wanted to prove that we actually need immune cells at the site of damaged nerves [part of the central nervous system thought to be off-limits to the immune system] to reduce inflammation and help the healing process. So that year, we transplanted a particular type of immune cell to a nerve lesion and showed that these cells did in fact help with repair by lowering inflammation.

Are other scientists pursuing this line of research too?
MS: It's an emerging field, but there are several groups whose work is closely related and supports our findings, at Stanford and at universities in Canada and Portugal. [Additionally, a recent study in Nature found vessels in the brain's outer layer that appear to directly link the brain and spinal cord to the immune system.]

Getting back to your own research, you later found a barrier between the circulatory system and the brain that appears to let immune cells through on an as-needed basis.
MS: What we found in mice is that when the brain is in need of repair or help, whether that's from injury or normal age-related changes, it sends out a signal that reaches this interface on the brain side. Together with the immune cells on the other side, that signal activates a process that allows the immune cells into the brain, where they reach the site that's having a problem and assist in repair. That could mean removing Alzheimer's plaques—our research suggests that immune cells can help facilitate this— or reducing inflammation and scar tissue.

In one study in Science, we compared the tissue of young and old mice and found that there was a protein interfering with that barrier in older mice, so immune cells weren't getting through, which helped explain why they had reduced cognitive functioning. When we neutralized this protein, the impaired cognition was partially reversed. What that tells us is that when the interface isn't working, it may accelerate brain aging because normal age-related damage can't be repaired by immune cells.

So a malfunctioning gateway may keep the immune system from doing its job in the brain. But what about the state of the immune system itself—does that make a difference in brain health and functioning?
MS: My team's research suggests that it does. We found, in a paper in Nature Neuroscience, that immune-deficient mice produced fewer new neurons, and that their rate of neurogenesis improved when the immune system functioned better.

Your research has been done almost exclusively in mice. What makes you confident that the findings will apply to people?
MS: Of course, time will tell, and human trials will happen likely in the near future, but we have some hints that support our theory in humans. One is that in the study comparing the brain tissue of old and young mice, we also looked at samples of human tissue and found that same interfering protein in older human samples.

How has this changed the way you live? Are you more focused on your immune health than you used to be?
MS: Yes. In the past I thought immunity was important because it would help me fight off infections—now I'm more concerned with it because of the potential effects on my brain. We know that in humans poor nutrition, stress and lack of sleep can suppress the immune system. I travel a lot, which impacts my sleep, so I'm very aware of that, and I try to take care of myself and get enough rest. I'm also more careful about what I eat, which, in the past, I didn't care so much about. [Schwartz's book says deeply hued vegetables, probiotics and foods high in omega-3 fatty acids can help boost immunity, among others]. And while our previous research in mice used drugs to alter their immune systems, we're just starting to manipulate their immunity through nutrition to see how it impacts the brain.

So does this mean we should be focusing on building a more robust immune system to stay mentally sharp?
MS: It's difficult to separate cause and effect with the brain, but our findings suggest that a healthy immune system is a big factor in keeping the brain young and healthy. People were skeptical at first, and for good reason. This was a new, unexpected discovery, and when you have an unexpected discovery you have to wait and see if the science supports it. And, even though there's more to discover, I can say with confidence that the immune system affects the brain in ways that we couldn't anticipate years ago.


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