Friday, December 18, 2009

Follow up on Hygeine Hypothesis, Symbiosis, Parasites et al

This theory is up there with grand unified theory, God debate etc and honestly, its going to take more than our lifetime to uncover and comprehend completely and its understatement. Nonetheless, its fascinating and will have far reaching consequences which we cannot even begin to envisage. So, for the ease of following, I am going to club the microbes and parasites albeit the utility of microbes has more positive but as per these evolving theories both have a profound impact on who we are (earlier posts - here, here, and here).

Edge has great talk on now famous, "Toxo - The Parasite in the Brain" by Robert Sapolsky explaning how it makes mamalians attracted to felines and also how uniquely it is capable of identifying and disabling just one specific fear circuit in amygdala, which till date no neuroscientists hasn't be able to do.

"The first thing we did was introduce Toxo into a rat and it took about six weeks for it to migrate from its gut up into its nervous system. And at that point, we looked to see, where has it gone in the brain? It formed cysts, sort of latent, encapsulated cysts, and it wound up all over the brain. That was deeply disappointing.
But then we looked at how much winds up in different areas in the brain, and it turned out Toxo preferentially knows how to home in on the part of the brain that is all about fear and anxiety, a brain region called the amygdala. The amygdala is where you do your fear conditioning; the amygdala is what's hyperactive in people with post-traumatic stress disorder; the amygdala is all about pathways of predator aversion, and Toxo knows how to get in there.
Next, we then saw that Toxo would take the dendrites, the branch and cables that neurons have to connect to each other, and shriveled them up in the amygdala. It was disconnecting circuits. You wind up with fewer cells there. This is a parasite that is unwiring this stuff in the critical part of the brain for fear and anxiety. That's really interesting. That doesn't tell us a thing about why only its predator aversion has been knocked outwhereas fear of bright lights, et cetera, is still in there. It knows how to find that particular circuitry.
So what's going on from there? What's it doing? Because it's not just destroying this fear aversive response, it's creating something new. It's creating an attraction to the cat urine. And here is where this gets utterly bizarre. You look at circuitry in the brain, and there's a reasonably well-characterized circuit that activates neurons which become metabolically active circuits where they're talking to each other, a reasonably well-understood process that's involved in predator aversion. It involves neurons in the amygdala, the hypothalamus, and some other brain regions getting excited. This is a very well characterized circuit."

From the above research, he has some enlighting hypothesis...

"
On a certain level, this is a protozoan parasite that knows more about the neurobiology of anxiety and fear than 25,000 neuroscientists standing on each other's shoulders, and this is not a rare pattern. Look at the rabies virus; rabies knows more about aggression than we neuroscientists do. It knows how to make you rabid. It knows how to make you want to bite someone, and that saliva of yours contains rabies virus particles, passed on to another person.
The Toxo story is, for me, completely new terrain — totally cool, interesting stuff, just in terms of this individual problem. And maybe it's got something to do with treatments for phobias down the line or whatever it is to make it seem like anything more than just the coolest gee whiz thing possible. But no doubt it's also a tip of the iceberg of God knows what other parasitic stuff is going on out there. Even in the larger sense, God knows what other unseen realms of biology make our behavior far less autonomous than lots of folks would like to think."
A few years ago, I sat down with a couple of the Toxo docs over in our hospital who do the Toxo testing in the Ob/Gyn clinics. And they hadn't heard about this behavioral story, and I'm going on about how cool and unexpected it is. And suddenly, one of them jumps up, flooded with 40-year-old memories, and says, "I just remembered back when I was a resident, I was doing a surgical transplant rotation. And there was an older surgeon, who said, if you ever get organs from a motorcycle accident death, check the organs for Toxo. I don't know why, but you find a lot of Toxo." And you could see this guy was having a rush of nostalgic memories from back when he was 25 and all because he was being told this weird factoid ... ooh, people who die in motorcycle accidents seem to have high rates of Toxo. Utterly bizarre."

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You want to know something utterly terrifying? Here's something terrifying and not surprising. Folks who know about Toxo and its affect on behavior are in the U.S. military. They're interested in Toxo. They're officially intrigued. And I would think they would be intrigued, studying a parasite that makes mammals perhaps do things that everything in their fiber normally tells them not to because it's dangerous and ridiculous and stupid and don't do it. But suddenly with this parasite on board, the mammal is a little bit more likely you go and do it. Who knows? But they are aware of Toxo."
"There's a long-standing literature that absolutely shows there's a statistical link between Toxo infection and schizophrenia. It's not a big link, but it's solidly there. Schizophrenics have higher than expected rates of having been infected with Toxo, and not particularly the case for other related parasites. Links between schizophrenia and mothers who had house cats during pregnancy. There's a whole literature on that. So where does this fit in?
Two really interesting things. Back to dopamine and the tyrosine hydroxylase gene that Toxo somehow ripped off from mammals, which allows it to make more dopamine. Dopamine levels are too high in schizophrenia. That's the leading suggestion of what schizophrenia is about neurochemically. You take Toxo-infected rodents and their brains have elevated levels of dopamine. Final deal is, and this came from Webster's group, you take a rat who's been Toxo-infected and is now at the state where it would find cat urine to be attractive, and you give it drugs that block dopamine receptors, the drugs that are used to treat schizophrenics, and it stops being attracted to the cat urine. There is some schizophrenia connection here with this."

There you go, that darn
dopamine again ... but I will keep my promise. Well, next one is a follow up piece on the microbes, nothing new but now there seems to be an unaminity among the researchers on the humility of "not knowing anything".

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Bacteria, viruses and fungi have been primarily cast as the villains in the battle for better human health. But a growing community of researchers is sounding the warning that many of these microscopic guests are really ancient allies.
Having evolved along with the human species, most of the miniscule beasties that live in and on us are actually helping to keep us healthy, just as our well-being promotes theirs. In fact, some researchers think of our bodies as superorganisms, rather than one organism teeming with hordes of subordinate invertebrates.
The human body has some 10 trillion human cells—but 10 times that number of microbial cells. So what happens when such an important part of our bodies goes missing?

Well, all I can say is ... oops  ( and did a tiny "thingee" had hand in making of  Hitler and Gandhi?)

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