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  • Alex Cloherty

Do microbes affect my brain? Part I

This question is nicely situated at a crossover between neurobiology, microbiology, and immunology. And like you may remember your high school biology teacher saying, we have to understand first structure, then function to get to the root of this question.

The brain is a special place in the human body. This is not only because its function gives us our sense of self; it is also special in an immunological way. The brain is separated immunologically from the rest of the body: stuff that roams around through our livers, intestines, arms, and necks can't get through to the brain. The reason behind this is a structure called the blood-brain barrier (BBB).

The BBB is simply a bunch of cells packed really close together along a membrane, like sardines in a tin. This structure gives rise to its function: a bodyguard (or should I say "brainguard"?). Anything that gets by the BBB bodyguard will be screened first. If the BBB doesn't find it suitable for the brain, then it won't get through.

As with all body parts and bodyguards, the BBB has its limitations. Sometimes, microbes can indeed affect our brains. Research has started to come out, for instance, about our "good" gut bacteria affecting brain function. This is thought to most likely be by 1) stimulating nerves near our gut to send signals to the brain, or 2) releasing really small molecules that can cross the BBB to "press some buttons" in the brain. However, this research is quite new and the chatter between the "good" bacteria and the brain is not extremely well understood yet. For this reason, I'll focus on the "bad" microbes first - with an update coming in the future about the "good" ones.

There are three major ways that the "bad" bacteria can get into our brains – and are they ever sneaky! The first way is by releasing toxins, which are very small molecules that can cause harm to specific parts of the body. Some toxins, for example those released by Bacillus anthracis, which causes anthrax, can damage the BBB, allowing other stuff coming after it to also cross. This subsequent stuff might be more toxin, or the microbes themselves. This is perhaps the simplest mechanism used by the "bad" bacteria: causing structural damage to the BBB to create a makeshift door.

A second way that "bad" bugs can get to the brain is actually by transporting themselves along nerves. Viruses like rabies can use the nerves that connect your brain to the other parts of your body like railroads. There are always trains going along these railroads to support normal bodily functions: rabies is a Wild West train hijacker that can ride straight to the brain, sneakily bypassing the BBB!

Finally, a third way that "bad" microbes can reach the brain is – even weirder than nerve hijacking – by using a "Trojan Horse" strategy. HIV is an example of this. The virus is able to enter immune cells that normally travel up to the BBB, and sit inside them just like the Greek soldiers in the original Trojan Horse. Normally, the immune cells that help make up the BBB have to be replaced as they get older. HIV takes advantage of this process by actually speeding up the rate of cell replacement in the BBB, and invading the brain from the very wall meant to protect it.

This week's post was an overview of how the "bad" microbes get to our heads. But don't despair: the "good" microbes can get to our heads, too! Stay tuned for a more positive part II.

Until next week,

- Alex

PS: If you're interested in reading more about these topics, here are a few papers I read while preparing this post!

Ivey, N. S., Maclean, A. G., & Lackner, A. A. (2009). AIDS and the blood-brain barrier. Journal of Neurovirology, 15(2), 111–122.

Nardacci, R., Ciccosanti, F., Marsella, C., Ippolito, G., Piacentini, M., & Fimia, G. M. (2017). Role of autophagy in HIV infection and pathogenesis. Journal of Internal Medicine, 281(5), 422–432.

Saylor, D., Dickens, A. M., Sacktor, N., Haughey, N., Slusher, B., Pletnikov, M., … McArthur, J. C. (2016). HIV-associated neurocognitive disorder — pathogenesis and prospects for treatment. Nature Reviews Neurology, 12(4), 234–248.

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