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Re: VERY interesting theory on AD time lag...

Posted by Adam on November 8, 1999, at 17:36:01

In reply to VERY interesting theory on AD time lag..., posted by Bruce on November 8, 1999, at 12:30:02

I've read with great interest about the very exciting discovery of neuronal stem cells,
and the therapeutic implications of adult neurogenesis. From what I understand, however,
the rate of neurogenesis in the adult brain is very small (so small in fact that for years
many experts have dismissed it as a possibility, and it's only with sensitive DNA labelling
and exhaustive histological examination that you can detect it.) Driving up the rate of
neurogenesis by less than a factor of two, while certainly remarkable in itself, doesn't
seem to me to be nearly as profound, potent, or extensive as other biochemical changes caused
by Prozac. How did the investigators make this leap when so many other plausible theories

Perhaps this is too simplistic, but if one were to realise improvement in mood from increased
neurogenesis in the hippocampus, wouldn't one's memory improve also? And since decreased
neurogenesis in the hippocampus (and other parts of the brain) is a normal function of aging
in the depressed and euthymic alike, why wouldn't giving boosting serotonin in the "healthy"
be a good idea? It would preserve a youthful state in the brain, seemingly.

I get their logic, sometimes. The association with Prozac-induced neurogenesis (and lets not
forget this could be bad for anybody) and antidepressant effect (or its latency, for
that matter) is really pretty thin, if you asked me. I wouldn't go around saying the things
these guys are saying. I'd say it was an interesting result, but I wouldn't even begin to
speculate on benefits or potential harmful effects. Clearly these guys are looking for more
funding from Lily, and I don't applaud their cynicism. But kudos for the intuitive leap that
lead to this discovery.

> Article from New Scientist magazine:
> PROZAC stimulates the birth of new brain cells in rats, say scientists from New Jersey. The finding gives clues to what causes depression in people, how drugs like Prozac relieve it and why the effect takes so long to kick in.
> Just over a year ago, researchers showed that people grow new neurons all the time. This overturned a long-held belief that brain cells, unlike cells in other parts of the body, are not replaced when they die.
> Barry Jacobs and Casimir Fornal at Princeton University put together findings from several different brain studies. They knew, for instance, that depressed people have a smaller hippocampus--a structure that is involved in learning and memory--than healthy people.
> They also knew that chronic stress can slow neuron birth, or neurogenesis, in the brains of rodents. Stress is thought to contribute to depression. "A little light went on in my head," says Jacobs. "It just occurred to me that maybe this is what depression is all about."
> Jacobs and Fornal went on to show that activating one type of receptor for the neurotransmitter serotonin in rats' brains increased the birth of neurons. So they decided to see if Prozac, which belongs to a class of drugs known as selective serotonin re-uptake inhibitors (SSRIs), would have the same effect. SSRIs prevent serotonin from being mopped up, leaving more of it around to transmit messages.
> The team gave daily injections of Prozac to five rats for 21 days. Five control rats were injected with saline. During the final 7 days, they also gave the rats a chemical called BrdU, which labels new neurons. When they examined the rats' brains, 69 per cent more new neurons had appeared in the brains of the Prozac-treated rats compared with the controls.
> Jacobs and Fornal believe that the waxing and waning of neurogenesis in the hippocampus may be an important factor in explaining why people slump into depression and why they recover with SSRIs. It may also explain why Prozac takes several weeks to improve mood. "The time needed for these newly generated cells to mature and make appropriate connections provides an explanation for the 'therapeutic lag' in antidepressant therapy," Jacobs told the meeting.
> Jacobs thinks serotonin could also help to treat other neurological diseases, such as Alzheimer's. But he cautions that it probably won't be of use to healthy people: "Their level of neurogenesis might already be optimal."




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