Eric Kandel – Investigating the biology of post-traumatic stress disorder (59/80)



Eric Kandel (b. 1929) is an American neuropsychiatrist. He was a recipient of the 2000 Nobel Prize in Physiology or Medicine for his research on the physiological basis of memory storage in neurons. He shared the prize with Arvid Carlsson and Paul Greengard. [Listener: Christopher Sykes].

TRANSCRIPT: So that was sort of the major thing we looked… We also looked a little bit at post-traumatic stress disorder. This came out of my walking through the lab and telling people, you know, one example of a functional prion is a biological curiosity, two examples is a biological principle. Let’s find another example. So Joe Rayman in my lab, who’s unbelievably gifted, scoured the literature, and found that there is in many cells something called TIA, T cell intracellular antigen, that forms aggregates in cells. And these aggregates… even the person who studied it suspected they may have prion-like properties. So we put it in the yeast and we tested it rigorously and we found classic features of prion properties: forms aggregates, self-perpetuating, SDS resistant, etc. And he is beginning to explore what it does. And it turns out that it’s involved in post-traumatic stress disorder. It’s a protective factor, but it’s a protective factor only in female mice. If you knock it out, female mice show a much more profound response to post-traumatic stress disorder. And it turns out, it seems to be a sex-specific splicing factor of the glucocorticoid receptor. So we’re really trying to pin this down, and we’re close to doing it. We also raised the question, there must be a male-specific splicing factor, and we’re looking for that as well. Anyway. We’re having a very good time with that.

Some time ago, way before the experiment with Scott Small and Gerard Karsenty we thought… actually Denise’s idea…. Wally Gilbert, who’s a wonderful molecular geneticist is a good friend of ours. We were having dinner together one night, and I was telling him about the early experiments with PKA and aging mice. And Denise said, there’s a little red pill here, and you guys should form a company. So we’ve formed a company for age-related memory loss. Actually, Scott Small was on the board. And after a while we sold it to Hoffmann-La Roche. And at the time we sold it we had several drugs that were better than phosphodiesterase inhibitors that were then available, but the FDA did not accept age-related memory loss as a distinct entity. In the last year, it’s changed its policy but 10 years ago when we were doing this, there was nothing like this going on. So I think Hoffmann-La Roche is in a good position now, but…

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