Axons Can Be Regrown

The axons that link neurons in the nervous system can grow to great length, up to several feet long in human limbs for example. Thus it isn't enough just to be able to replace or repair cells in the nervous system when building regenerative treatments, the axons must also be considered. Here researchers demonstrate a first step towards axon regrowth, which is to get it to happen at all. Creating restoration of function is the next step that must be built on this foundation:

Axons in the central nervous system (the CNS, consisting of brain, eyes and spinal cord) cannot regenerate after an injury in higher animals such as mice and humans. Earlier work had shown that axon growth can be blocked by disabling the proteins B-RAF and C-RAF, part of the RAF-MEK growth-signaling pathway involved in neuronal development. This growth-signaling pathway is inactive in adult animals.

To isolate the effects of B-RAF in the nervous system, [researchers] genetically engineered mice so that B-RAF in neurons could be turned on at will. Activation of B-RAF enabled normal growth of sensory axons in mouse embryos that lacked a crucial nerve growth-signaling pathway and would normally not develop proper sensory innervation.

The researchers then tested whether boosting B-RAF in adult mice could help repair injured sensory axons, which are not part of the CNS. In mice with identical neuronal injuries, those with activated B-RAF showed significant axon regrowth. The regenerating axons even reconnected with the spinal cord, seemingly unchecked by the inhibitory cues that normally inhibit regeneration in the adult spinal cord.

Next, the researchers set their sights on the more elusive goal - regeneration inside the adult CNS. In an encouraging step towards fulfilling that dream, the researchers found that B-RAF activation strongly enhances axon regeneration in injured optic nerve. Moreover, when they combined B-RAF activation with another manipulation, the inactivation of the PTEN gene, the combined axon regeneration was even greater than they had expected from a simple additive effect.



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