Neuronal Regrowth after MDMA Neurotoxicity

j paget neoplastic_1 at yourmom.com
Fri Apr 19 08:52:52 EST 2002


"Xiphihumeralis" <xiphi at yourmom.com> wrote in message news:<ArPv8.5634$rC2.1760802 at twister.rdc-kc.rr.com>...
> Greetings --
> 
> I am currently preparing a presentation on the possible neurotoxicity of
> MDMA (club drug ecstasy).  I am familiar with how brings about the drug's
> effect through it's interaction with the serotonergic pathways and the
> serotonin transporter protein SERT.  One main study that I am referencing is
> by Dr. George Ricaurte, perhaps some of you are familiar with it...Squirrel
> monkeys are given MDMA b.i.d for 4 days.

i'm sure others on this group will let you know what they think of
ricuarte's work in general-- be aware these are extended, large doses
that bear little relevance to what happens to humans at recreational
doses.
  
> as well as other portions of the brain are physically studied from control
> subjects, from MDMA subjects 2 weeks post-experiment, and other MDMA
> subjects 7 years post MDMA experiment.  Not surprisingly, there was a marked
> decrease in the density of serotonin neurons in the subjects 2 weeks
> post-experiment.  However, the 7-year group STILL had significant neuronal
> damage, however it was LESS severe than the 2-week mark.  (Image is here
> http://www.nida.nih.gov/teaching4/largegifs/slide18.gif) If the theory in
> question is "neurotoxicity", how do these neurons apparently repair
> themselves?  

i didn't follow your link, but i think they looked at SERT as the
marker for damage. SERT is not a marker for the # of neurons. you can
have 1000 neurons expressing a little SERT, or you can have 10 neurons
expressing a lot of SERT.  The way these things are usually
quantified, there's no reliable way to tell just from SERT stains.
Only double labelling with, for instance, neuron-specific enolase or
something will show that there are few serotonin producing neurons.
even that method has its problems.

> Is there a new theory out there that certain neurons CAN be
> repaired?  I have always been taught that neurons are inherently in the Go
> phase, and do not undergo mitosis, thus do not repair from damage. 

go to pubmed and look up "Gage F" and "Gould E".  there_is_a new
theory, adult neurogenesis, though its never been shown that
serotonergic neurons can be replaced.

> current school of thought of this neurotoxicity is formation of free
> radicals...could that possibly cause genetic mutations?  I still don't see
> how these neurons can repair and/or regrow, albeit in many cases, the growth
> was abnormal.

the free radicals, or whatever is causing the damage, are mostly
confined to the tips of the neurons, so the pathology they see is
called "axonopathy". this doesn't necessarily result in cell death
(and btw for a genetic mutation to occur, free radicals would have to
make it back to the cell body). *axons* can regrow even after MDMA
damage in animal models, though they're usually kind of stunted (see
pubmed, "azmitia", i think).  axon outgrowth doesn't require a neuron
to re enter the cell cycle, its mostly a matter of cytoskeletal
remodelling.

hope that's helpful.

j




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