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Brian Scott brians at interlog.com
Wed Jan 5 02:55:17 EST 2000

JoshCahoon wrote:
> I'd like to get a feel for this controversy. Various publications, including
> the NYT today, say that findings indicating neurogenesis in humans have long
> been resisted by the neuroscientific community, being contrary to dogma. On the
> other hand, my professor at the Salk told me their really isn't a controversy.
> Is there? Perhaps just over whether new neurons are functional?

Neurogenesis in adult animals had been reported as far back as 30 years
ago by Joseph Altman and others, but until fairly recently the study of
adult neurogenesis has been pretty slow.  In the last few years though
things have really exploded.  The evidence for adult neurogenesis is
pretty solid in rodents and birds, and there are lots of examples now in
primates and many other mammals.  Some of the early primate work failed
to find convincing evidence of adult neurogenesis.  Since this work was
produced by a big guy (Rakic) in the anatomy field, it was generally
believed that primates were the exception.  Recent work by Gould and
Gage's people as well as Rakic have now demonstrated adult neurogenesis
in several primate species.  It had been said that the production of new
neurons in adulthood would disrupt existing circuitry and therefore
memory, and this is why neurogenesis in higher animals stops after
development.  [Elizabeth Gould is now suggesting that adult neurogenesis
may actually be important for certain types of memory.]

Kempermann and Gage used essentially the same techniques from the animal
work to show neurogenesis in the hippocampus of adult cancer patients
ranging in age from 30s to 70s I think.  It's pretty convincing to me
but there are still criticisms with respect to the BrdU technique and
whether it's really labelling new cells.  It's the same criticism of the
technique since it was invented. Maybe the BrdU is being incorporated
into dying or injured cells that manage to survive. Some have said that
maybe this (neurogenesis) is just a phenomenon associated with cancer or
its treatment.  There's at least one paper I know of since then that
looked for a marker of cell division in tissue taken from epileptics
that claimed there was no evidence of a subgranular proliferative
zone...where the neurogenesis is supposed to occur.  I don't think his
technique was sensitive enough though.  Anyway, besides the hippocampus
there's also evidence for neural stem cells which may be generating
neurons around the ventricles.  I'm less familiar with this though. 
Gould recently reported neurogenesis originating around the ventricles
and sending neurons to the association cortex of monkeys.  Maybe this is
happening in humans too.

With respect to the functionality of these cells, they look like the
other cells nearby and send projections to the same targets and express
the same marker proteins.  There is evidence of synapses on them too. 
Until someone can actually patch-clamp from a cell which was definately
born in adulthood, there will always be those that question whether they
are functional or not.  In animals, their production is very tightly
regulated by adrenal hormones and probably by input to the dentate
gyrus.  It's very likely they're being used for something.  

Brian Scott           |     Institute of Medical Science &
brians at interlog.com   |  Bloorview Epilepsy Research Programme
                      |        University of Toronto
                      |           Toronto, Canada

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