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Central Nerve Regeneration in Zebrafish

One of the biggest challenges faced by medical neuroscience is the inability of neurons in the mammalian central nervous system to regenerate after injury.  This makes traumatic events such as spinal cord injury or stroke into lasting problems for patients.  However, the adult zebrafish does have the ability to regenerate neurons after injury.  The mechanisms responsible for this regeneration are being closely studied in the laboratory of Dr. Michael Brand at the Technische Universität in Dresden, Germany.  Their long-term hope is that the process can one day be applied to human patients.

Recently published work from this laboratory builds on a study they published last year (Kroehne et al., 2011; Kyritsis et al., 2012) which showed that radial glial stem cells, precursors to neurons, react to injury by generating neuroblasts that migrate to the site of the lesion.  Furthermore, these neuroblasts gained synaptic contacts and were stable for at least 3 months.

Because radial glial stem cells express receptors for inflammatory molecules and because inflammation is a part of every injury, the authors chose to examine the effects of inflammation on regeneration.  Using microinjection of Zymosan A to induce an inflammatory state in the brain, they found new neuronal growth at the site of injury.  In addition, no neuronal generation was seen when brain injury was induced in immune-suppressed zebrafish, while zebrafish in the control group did regenerate neurons after brain injury.

Next, the authors identified a role for the gene Cystlr1, which codes for a cell surface protein that binds leukotrienes.  Leukotrienes are produced by white blood cells as part of the inflammatory response to injury.  When the researchers blocked Cystlr1 activity, neuronal regeneration was reduced.  When leukotriene alone was applied using microinjection into zebrafish brain, radial glial cells indeed proliferated.

What do you think?

Will cellular mechanisms identified in zebrafish someday help human patients?

Why would inflammation have this kind of effect in fish, but not mammals?

Further Reading:

Kroehne V, Freudenreich D, Hans S, Kaslin J, Brand M. (2011).  Regeneration of the adult zebrafish brain from neurogenic radial glia-type progenitors.  Development.  Nov;138(22):4831-41.

Kyritsis n, Kizil C, Zocher S, Kroehne V, Kaslin J, Freudenreich D, Iltzsche A, Brand M. (2012). Acute inflammation initiates the regenerative response in the adult zebrafish brain. Science.  Nov 8. [Epub ahead of print]


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