Tuesday, February 21, 2012

Of Mice and Men and The Question of Free Will

     We presume we run the show, choose our profession, our partner, our path. Of course we've heard about instinctual behavior, hard-wired stuff that is dictated by our evolutionary history. And we can accept such theory that explains how some of our evolutionarily prescribed choices are actually quite adaptive, like being drawn to characteristics associated with intelligence and fertility. But what if we were the pawns of parasites.

     Here's a David and Goliath story that hits close to home.

     We humans are very hospitable. Not only do we host our social circle in our homes, but our bodies are colonized by bacteria whose population dwarfs our own cellular constituents. (see blog entry on gut flora). These squatters can affect all sorts of things such as our metabolism, determining our risk for obesity or diabetes.

     One trespasser that has recently drawn researchers interest is Toxoplasmosis, a protozoan parasite. Those aware of toxo were enlightened when pregnant and warned of the dangers cats posed. Toxo's peculiar life cycle holds the key to this story.

     Toxo can only reproduce in a cat's bowels. It then exits in the feces and has the bizarre task of figuring out how to return to this feline homeland. Fortunately for toxo, rodents eat cat feces. And as we all know, cats eat rodents. But evolutions laboratory, unsatisfied with toxo's rate of return, lent a helping hand. It provided toxo with a way of changing rodent behavior. This is a very clever parasite.

     First, a few basics on rodent life. Not surprisingly, rodents hate the smell of cat urine and do everything possible to avoid it. A toxo-infected rodent not only looses this aversion, it appears drawn to it.

     To make a long story short, toxo rewires the rodent brain, highjacking the anxiety circuit for this particular stimulus and making it fire like a sexual reward pathway. It does this by injecting dopamine, the pleasurable neurotransmitter that is released by cocaine and other euphoriants.

     The specificity of toxo's brain surgery is exquisite. Toxo-infected rodents still fear bright lights and open spaces, like healthy ones. They don't wander around engaging in all sorts of risky behavior. The only thing that changes is their reaction to cat urine which goes from "get me outa here" to "I like that!". And that's all toxo needed to return to the feline promised land. If you give toxo-infected rodents a drug that blocks dopamine, their behavior normalizes.

     "Great story, so what", you say. Well it seems we humans can also be toxo stooges. Toxo-infected humans are 3-4 times more likely to die in car accidents caused by reckless speeding then non-infected. And an old ER saw warns docs to check motorcyclist organ donors for toxo before harvesting their vitals. So while this infection won't get us into a cat's gut, it appears to have the same effect, short-circuiting an anxiety response and making high risk behavior quite alluring.

     To lend credence to this story, imagine what organization might be interested in helping people do life-threatening things that every human instinct resists? Bingo, the military. And they've poured money in toxo

     For our purposes, this story is meaningful because it highlights the import of our relationship with those organisms living inside us. This microbiome, represents a new frontier in understanding both health and disease.


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