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June 4, 2010
OCD Linked to the Immune System?
Now here's one that I certainly didn't expect: there's a mouse model of obsessive-compulsive disorder, where the animals have a mutation in the Hoxb8 gene. These animals spend huge amounts of time repetitively grooming themselves (and their cagemates), and eventually remove so much hair that they give themselves lesions. From what I can see, they're doing the usual moves that mice do, but spending a lot more time doing them. And it doesn't seem to be something due to insensitivity to pain; the animals have some sensory alterations, but disrupting Hoxb8 in the spinal cord only doesn't lead to the grooming phenotype.
A new paper from a group at University of Utah reports that the brain signature of Hoxb8 mutation is found only in a population of microglia, one variety of the support cells that surround neurons. Hoxb8 was already known to affect the formation of blood cells, so this cohort of microglia (about 40% of the total in the mouse brain) look to be derived from the same precursors. So this study went the direct route: they did bone-marrow transplants on the mutant mice so that normal Hoxb8 cells would be produced. And over a time scale of weeks,most of the mice stopped their overgrooming. Meanwhile, the group also transplanted mutant bone marrow into normal mice, whereupon some of these mice began obsessively removing hair. (Here's the Nature News article on all this).
This seems to be the first time that anyone's linked microglia with behavior. The focus, naturally enough, has been on the neurons themselves and their connections, but it looks like we're all going to have to broaden our outlook. There are some things that need to be cleared up here, though. For one thing, it's not certain that these mice are truly an analog of human OCD - even the form of it that involves obsessive hair-pulling. Other obsessive mice types are known, and it'll be quite interesting to see what shape their microglia are in. At the same time, it would be worth going the other way, and seeing if the pharmacological agents used for OCD have any affect in the Hoxb8 mice, too.
Another thing that this study demonstrates is that at least one population of microglia are being continually renewed in the brain from the bone marrow. What the different roles are of this group versus the "resident" microglia is yet to be figured out. My mental picture of the brain has always been this protected zone, with very little allowed to cross in or out, but that's clearly incorrect.
But it looks as if we can say that someone has drawn a direct link between the immune/blood cell system and behavior in an animal model. Such things had long been suspected, but they've been very difficult to prove. Whether these mice have OCD or not, they've illustrated something new. This makes me wonder if various immunosuppressive drugs could have psychological and behavioral side effects that we haven't been picking up on - anyone who knows that field care to comment?
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