In mammals, embryonic neurons can regenerate, but in the central nervous system (CNS), this ability is lost as neurons mature during early postnatal development. Recreating the embryonic environment in the adult CNS might therefore help to promote repair following injury. One factor that inhibits regeneration is myelin, and modifying myelin itself might create a more permissive environment for neuronal regeneration. However, an alternative approach that is being explored is the modulation of the neuronal response to myelin. As Cai et al. report in the Journal of Neuroscience, myelin is not inherently inhibitory, and it can even promote axonal growth in embryonic and neonatal neurons. What causes this switch in responsiveness? And could adult neurons be induced to behave like their embryonic counterparts?

The authors previously reported that elevating the levels of the cyclic nucleotide cAMP in adult neurons enables them to regenerate their axons in the presence of myelin. In this new study, they examined whether endogenous cAMP levels change during development, and whether this might mediate the change in responsiveness to myelin. They showed that, in rat dorsal root ganglion (DRG) neurons, the cAMP level drops during early postnatal development, coinciding with the period in which these neurons lose their ability to regenerate in vivo .

The authors also tested the response of DRG neurons to an inhibitory component of myelin, myelin-associated glycoprotein (MAG). Normally, MAG promotes neurite outgrowth from neonatal DRG cells. However, if a downstream cAMP effector — protein kinase A — is blocked, these cells can no longer regenerate in response to MAG. By contrast, raising the level of cAMP in adult DRG neurons causes them to behave more like neonatal cells, as they now extend neurites in the presence of MAG.

So, for the first time, a three-way connection has been established between cAMP levels, the age of the neuron and its regenerative response to myelin. This confirms that raising cAMP levels in adult neurons causes them to behave as if they were much younger. If CNS regeneration is to be achieved in the adult, it seems that neurons should definitely not be encouraged to act their age!