Episode 140: Autoimmunity & the Brain with Donna Jackson Nakazawa

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New Scientific Discovery: the Immune Cells in Our Brain

If you’ve ever experienced brain fog, anxiety, or mood issues alongside your autoimmune symptoms, you’re not alone. Doctors know that mental health issues often increase with an autoimmune diagnosis, but it was always assumed this was simply an emotional response to living with the challenges of chronic illness. And indeed, that is part of it. But for many patients, it didn’t explain the severity of brain symptoms. A new scientific discovery has now filled in that missing puzzle piece. There are cells in the brain called microglia that are actually part of the immune system. And just as our body’s immune system can go into overdrive and cause chronic inflammation with autoimmune disease, the same thing can happen in our brains. My guest is science journalist Donna Jackson Nakazawa. Her latest book is called The Angel and The Assassin, and it’s all about these little brain cells and how they can help us or harm us.

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Show Notes

  • Intro (0:00)
  • Thank You to Our Podcast Sponsor: Paleo on the Go (2:34)
    • A frozen meal delivery service, 100% of their menu is compliant with the elimination phase of the paleo autoimmune protocol (AIP). They have over 5o items, including entrees, side dishes, broth, AIP-friendly bacon, and desserts.
    • Use the code PHOENIX for 10% off your first order.
  • Meet Donna:
  • Her Personal Experience with Autoimmunity & the Brain (3:47)
    • Guillain-Barre Syndrome left Donna bedridden in 2005, and it was a year before she could walk again. Simultaneously, she experienced severe cognitive impairment. As a science journalist, she always had the confidence of her brain’s ability to process complex information. She had an excellent memory. Now, she couldn’t remember words for common household objects and the names of close family members. She couldn’t do basic math and struggled to tie her children’s shoes. The sadness she felt was extreme – a level of doom and despair she had never before experienced. Yet when she brought these symptoms to her doctor, they were dismissed as a natural response to the stress of being paralyzed. Donna knew it had to be more than that. This began a decade-long journey into understanding the connection between inflammation in the body and inflammation in the brain.
  • The Science – Recent Discoveries in Microglia Research (7:36)
    • For hundreds of years, scientists believed that the brain was the one organ in the body with no immune system involvement – that it was “immune-privileged”. This was believed for 3 reasons: (1) A long-held belief in mind-body dualism since the time of Descartes, (2) The physical structure of the skull which doesn’t allow the normal inflammatory response that occurs elsewhere in the body, and (3) The blood-brain barrier which sits at the base of the brain.
    • Microglia were discovered in the 1920’s, but at the time they were dubbed “housekeepers of the brain.” It was believed their only role was to clean up dead neurons, like little robots. Recent scientific discoveries have cast these cells in a new light:
      • At Stanford, Dr. Ben Barres & Dr. Beth Stevens discovered that when brain synapses were tagged in the brain by a molecule called complement, they disappeared. This was unusual because that’s the same molecule that tags tissue in the body during autoimmunity, calling immune cells (macrophages) to the area which increase inflammation.
      • Dr. Stevens then opened her own lab at Harvard, and with the help of fellow researcher Dori Schafer, they were able to see microglia eating those synapses in a way that’s very similar to macrophage activity.
      • At Mt. Sinai School of Medicine, researchers discovered that microglia aren’t glial cells at all. In a developing fetus, stem cells differentiate into different types of cells. They witnessed microglia emerging from white blood cells and then traveling to the brain.
      • Finally, at the University of Virginia, researchers discovered lymphatic vessels (which carry immune cells throughout the body), traveling through the blood brain barrier and circulating in the meningeal spaces surrounding the brain.
      • Suddenly it was abundantly clear that the brain is not immune privileged, and that microglia are part of the body’s immune system.
  • Microglia: Angels vs. Assassins (22:41)
    • The harm that can be done when microglia become overactive:
      • Neurons are brain cells, and synapses are the connections between then. Our brain needs to communicate all the time through these synapses in order to understand the world and respond to it. When microglia become overactive, they prune healthy synapses, interfering with these connections.
      • Overactive microglia can also emit neurotoxins, which cause brain inflammation and interfere with the function of beneficial neurotransmitters such as dopamine and seratonin.
      • Overactivity of microglia is seen in many different conditions, including anxiety, depression, bipolar disorder, schizophrenia, Alzheimer’s disease, Parkinson’s disease, and more.
      • Things like a positive mindset, self-regulation, mood stability, etc. depend on healthy synapses in the brain.
      • While this can sound scary, it’s important to know this damage and overactivity isn’t permanent. New synapses can re-form, and microglia can be positively harnessed for repair and regeneration.
    • Beneficial roles played by microglia:
      • When the microglia are performing as intended, they are the good doctors of our brain. 10% of brain cells are microglia, and their role is to help the brain stay healthy and thrive.
      • If a neuron is struggling, they emit soothing factors that support neuron function.
      • They help create synaptic connectivity, rather than disrupting it.
      • When they do prune synapses, they do it wisely – just as a gardener would prune a tree for optimal health.
      • They also remove dead neurons, performing the housekeeping role necessary to keep the brain clean.
  • Thank You to Our Podcast Sponsor: Autoimmune Strong (31:45)
    • They are the one and only online exercise program designed for people with autoimmune disease, by a personal trainer who has autoimmune disease herself.
    • Andrea Wool knows what it’s like to lose your ability to exercise, and she knows how to help you regain that ability again. She’s an expert at the connection between autoimmune disease and exercise intolerance, and how to harness exercise in a way that’s anti-inflammatory rather than inflammatory.
    • Membership gives you access to videos that are designed for all body types – even people with severe joint pain or limitations getting up and down off the floor. The videos are short and easy to follow. They slowly progress in intensity and teach you how to find the level of exercise that’s safe for you. The program focuses on strength, flexibility, and cardio fitness. In addition to the videos, membership gives you access to a supportive online community and a monthly Q&A call with founder and personal trainer, Andrea Wool.
    • Listen to my interview with Andrea to learn all about exercise intolerance and why it’s a common side effect of autoimmune disease.
    • Join Autoimmune Strong and use the code PHOENIX for 10% off your first month.
  • What Causes Microglia to Become Overactive and Harmful? (33:32)
    • Similar to autoimmune disease, there are many root causes. Picture the immune system as a barrel. It can handle a lot of input: toxins, stressors, inflammatory foods, infections, etc. It’s working to keep us healthy all the time. But if it becomes overwhelmed and the barrel overflows, it starts to over-respond. This happens with autoimmune disease, and also with microglia overactivity.
    • While we often wish there was one cause that could be easily fixed, it’s also empowering that there are so many ways we can lighten the load on our immune system, and help restore its healthy function.
  • The Connection Between Autoimmunity, Inflammation, and Micgroglial Overactivity (36:00)
    • This is a tricky area to separate, because they often co-exist, but the research is too new to see if they always co-exist.
    • Autoimmune activity is when the immune system attacks body tissue (i.e. joints in rheumatoid arthritis, thyroid in Hashimoto’s, etc.)
    • While inflammation is always part of the autoimmune response, inflammation can also occur separately from autoimmune disease.
    • Microglial overactivity causes inflammation in the brain, but this isn’t considered an autoimmune response. The autoimmune designation is saved for diseases where you can actually see an attack on brain tissue, like autoimmune encephalitis.
    • Research in this field is too new to know if inflammation in the body and microglial overactivity in the brain always co-exist. But early studies are showing this is often true in everything from physical trauma to chronic pain, some autoimmune diseases, and psychiatric diseases as well.
  • New Treatments Based on Microglia Research (40:09)
    • Category 1: Understanding old treatments with new eyes.
      • Neurofeedback is a technique that addresses brain wave dysfunction. When microglia are functioning properly, they support optimal brain waves. When they are overactive, they disrupt brain wave activity. So, when neurofeedback is successful, it might be helping to restore proper microglia function.
      • Antidepressants take many weeks before people feel their effects. One reason might be that it takes that long for microglia to “reboot” and stop causing problems. However, research also shows that people who don’t respond to anti-depressants have higher inflammatory markers in the body, which might mean that microglia are playing an even bigger role.
      • There’s also a new understanding of the gut-brain connection. Microglia communicate directly with immune cells in the gut.
      • New research is also showing that fasting might suppress microglial overactivity.
    • Category 2: New treatments already being used in clinician offices.
    • Category 3: Future medicine which will require multiple clinical trials before they are proven safe and effective.
      • New tests which will identify when microglia are behaving positively vs. negatively in the brain. This will allow for more preventive medicine – catching conditions when they are still in a mild state and respond better to treatments. Many conditions – such as Alzheimer’s – involve damage to the synapses long before symptoms appear. These tests will also be able to show whether a treatment is effective.
      • New medications that will target neuroinflammation directly, and many being studied are similar to autoimmune medications. In fact, there was a recent scandal with Enbrel. The company suppressed knowledge that patients with rheumatoid arthritis who took Enbrel gained an unexpected benefit: a reduced risk of Alzheimer’s.
  • Destigmatizing Mental Health Disorders (54:35)
    • Microglial research has proven that mental illness is a physical illness, just like any other. It’s not a weakness in someone’s character. There was an artificial line drawn centuries years ago between the mind and the body. That line never actually existed. People suffering from mental illness deserve the same empathy, understanding, and excellent medical care as any other illness.
  • Outro (56:44)

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