I recently read an article about zebrafish regenerating myelin sheath after mechanically demyelinating. I am interested in studying their ability to regenerate after a non-mechanical demyelination such as what happens with MS, and a drug or chemical that could mimic these affects would be incredibly helpful. Research has led me to the drug ethambutol but the demyelination that occurs with this drug is rare and typically reversible.
Dear Hunter Clark,
the cuprizone toxicity modell nicely recapitulates some key features of demyelination.
In fact, there are studies associating cuprizone toxicity with oligodendroglial degeneration and the formation of myelin balloons similarly to that seen in mitochondrial diseases (generally in lower doses), whereas in higher doses, cuprizone toxicity leads to defiinitive demyelination and oligodendroglial apoptosis. From this aspect, it is often considered as model for primary progressive MS as well.
Here are some nice publications:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4187018/
http://www.ncbi.nlm.nih.gov/pubmed/23890807
Hope this helps!
Best regards,
Levente
you could also consider using lysophosphatidylcholine (a.k.a. lysolecithin, LPC).
This is a well characterized agent that causes demyelination by acting as a detergent to solubilize myelin. At the right concentration, the effect on underlying axons is minimal and there is a capacity for endogenous repair.
We use it by direct injection into the mammalian spinal cord, but I have also seen it used for multiple in vitro systems (slice cultures for instance) and thus conceptually it could be used in a zebrafish in vitro system.
Indeed, though ethidium bromide as well as lysolecithin may also have a dose-dependent effect in this respect, as they have also been reported to induced myelin vacuolization, similar to that seen in the cuprizone model.
We have a recent publication with mice demonstrating myelin vacuolation in the discussion of which there is a comprehensive table (Table I) reviewing compounds leading to myelin vacuolation. Most of them have also been associated with demyelination, which divergences may be dose-dependent or related to the way of administration. The table includes the compounds so far discussed as well. It may be worth checking them one-by-one.
http://www.termedia.pl/Histopathological-comparison-of-Kearns-Sayre-syndrome-and-PGC-1-deficient-mice-suggests-a-novel-concept-for-vacuole-formation-in-mitochondrial-encephalopathy,20,27226,1,1.html
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