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Re: Hmmm: my two cents worth

Posted by Adam on November 10, 1999, at 0:26:56

In reply to Hmmm: my two cents worth, posted by Sean on November 9, 1999, at 12:25:26

>
> But hey, I'm talking out my ass...
>
I guess that never stopped me :).

I've been thinking more about the implications of increased neural stem cell proliferation
rates, and the implications could be disturbing.

Since we're all speculating wildly (as the investigators mentioned above clearly are) here's
another thing I thought of...

Stem cells exist all over the body. The paradigm is the hematopoietic stem cell that exists in
the bone marrow, and neural stem cells from adult tissues have been grown in culture since the
mid-90s. The first real evidence of a specific stem cell type doing its job in situ was reported
in the journal Cell last January. They showed that ependymal cells (cells that line the
ventricals) could divide and give rise to both neurons and glial cells (specifially astrocytes).
These cells can migrate in response to signals both known and unknown and find their way to where
they are needed (to form scar tissue in a spinal cord injury, for example, or replenish neurons
in the olfactory bulb).

All stem cells have the quality of being "multipotent": they divide and give rise to two new cells.
One is another stem cell like itself, and the other is a cell that will terminally differentiate
into a specific cell type. By "terminally differentiated" I mean that even if the cell can divide
further, it will give rise only to cells just like itself. Neurons are "quiescent"; as far as we
know, they don't divide at all.

Stem cells keep dividing as long as they last. Now, all somatic cells (non-germ cells), including
stem cells, can only divide so many times. All chromosomes in cells contain repetitive, GC-rich
sequences of DNA stuck on on the ends of the molecule called telomeres. Telomeres are synthesised
normally in somatic cells only during embryogenesis. Then enzyme that synthesizes them (telomerase)
isn't active in somatic cells beyond this point. The telomeres function to keep the chromosome
intact-they provide a sort of glue at the end that prevents it from unravelling and undergoing
catastrophic rearrangements. The trouble is, every time a cell divides, it loses a bit of the telomere.
Eventually, the telomere reaches a certain length, which is sensed by the cell. When the cell
reaches this point, it commits suicide. This is an evolutionary consequence of aging. Every cell
has this built-in clock, and it leads to death unless telomerase is active (only in germ cells and
cancerous cells, which are immortal).

If my understanding of neural stem cells is correct, they divide when needed to give rise to cells
that go where they're needed (just like hematopoietic stem cells). It could very well be that the
aging brain starts to decay because our complement of stem cells decreases (as it does in all tissues)
as time passes and cells reach the end of their life span. This will happen sooner or later depending
in part on how many times the cell has divided at a given time. If this rate of division is sped up,
what could this mean? One possibility (and a scary one at that) is that, like the candle burning
twice as bright half as long, you run out of neural stem cells earlier than you would have otherwise.
While it's true you may have a few more neurons than the average person when you reach that point,
if you have fewer stem cells later in life, you might not get the new growth that you need when and
where you need it. If what these guys are saying about Prozac is true, I see this as a distincly
possible scenerio, at least as possible as their functional association with antidepressant effect.
It also could be true of any drug that boosts serotonin levels, if serotonin is in some way the trigger
of a growth signal. This signal could just be mimicking stress (such as injury), and that's why these
cells are dividing 60-some-odd% more.

Kind of creepy, if you ask me.


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poster:Adam thread:14806
URL: http://www.dr-bob.org/babble/19991108/msgs/14911.html