This post is the second in a series that will highlight contributions from various scientific disciplines that have furthered our understanding of how the brain and nervous system affect how we think and behave. Click here for the previous installment about ion channels, and look out for more posts in the future!
One of the first things you’ll learn about if you start studying the brain is that it is made of cells called neurons. While neuroscientists have a decent understanding about how neurons work, it turns out that at least half of the brain is actually made of non-neuronal cells called glia*. Glia, named after the Greek word for ‘glue,’ were initially thought to be a type of connective tissue in the nervous system, acting just as scaffolding, while the neurons did all of the communicating. In the last couple of decades, the growing field of neuroimmunology has highlighted the importance of a certain kind of glia: microglia, the brain’s resident immune cells.
I like to think of microglia as the National Guard of the Brain, with landscaping as their day job. Microglia spend a lot of their time cultivating neurons, helping them grow and connect properly, and cleaning up natural waste products that accumulate with normal ‘everyday’ activity. As little neuronal gardeners, microglia participate in synaptic pruning, a process whereby unneeded connections get trimmed from a neuron’s dendrites. However, if something foreign releases an immune distress call in the brain, these peaceful landscapers spring into action by withdrawing their long, spindly, ‘ramified’ arms. Prepared for war as stubby-armed blobs, they are ready for action, ready to chomp (through a process called phagocytosis) any object deemed harmful to the brain or nervous system at large. This process is very similar to the way that white blood cells get rid of invading pathogens in other parts of the body.
Generally, there is a nicely regulated amount of microglia switching between their quiet ‘surveillance’ state and their militant ‘activated’ state, in which they eat stuff as part of their daily maintenance duties. When activated, microglia actually send little immune signals to nearby microglia to get help cleaning up whatever trash needs removing. However, this ability can cause problems for microglia if there’s a huge shock to the system in the form of a chemical or physical injury. Essentially, too many microglia can get stuck in their activated state, due to both the severity of the injury as well as the local echo chamber of immune distress calls.
Recently, neuroscientists that study almost every nervous system disorder have found that activated microglia play some role in what they study. Neuropathic pain? Depression? Alzheimer’s? Substance abuse? Check, check, check, check – you get the picture. So if there are all of these microglia stuck in activated states in all of these disorders, is there anything we can do about it? In the past decade, a fair amount of preclinical and clinical trials have looked into the possibility of wiping out microglia as a treatment for disease. Often referred to as ‘microglial depletion’ or ‘microglial repopulation’ in research papers, I think of it as a ‘microglial reboot.’ 95% of the time, turning your computer off and on again will fix the issue if it’s stuck on a process. In the case of neurological disorders, there is a drug called PLX5622 that is able to kill off most microglia when introduced into the system. However, microglia populations are able to spring back a day or so after the drug is cleared from the body. This process of wiping the brain’s immune response clean has provided some interesting findings in animal models. Researchers have found that eradication of microglia improves cognition in mice genetically engineered to resemble Alzheimer’s symptoms. While no pharmacological treatment is a silver bullet, a microglial reboot is an intriguing way to study the role of the immune system in neurological disorders.
As I’ve spent time learning about microglia and neuroimmunology, I’ve thought a lot about the phrase “healthy body, healthy mind.” Thinking back on the times when I’ve been physically sick, I think about how those periods are usually accompanied with a feeling of mental sickness, be it increased stress, cognitive ‘fuzziness,’ or fatigue. Knowing that microglia are immune cells that respond to infection, in addition to keeping neurons happy, sheds a bit of light on why I feel sick when I am sick. I’m excited to see further neuroscience research on this topic as we learn more about the complex ways in which our brains communicate with our bodies.
*For further reading about the exciting nerd controversies surrounding exact glia numbers, read this.