Chapter 27 A role for cAMP in regeneration during development and after injury

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This chapter presents evidence to support that neuronal cAMP levels are a key element dictating the regenerative capacity of neurons. First, exposure of neurons to neurotrophins prior to their encounter with myelin inhibitors overcomes the inhibition, and this is mediated by elevation of neuronal cAMP levels. Second, there is a developmentally regulated decrease in the endogenous neuronal cAMP levels, which marks the developmental loss of the regenerative capacity of neurons. Finally, transaction of sciatic nerve leads to an elevation of the cAMP levels in dorsal root ganglion (DRG) neurons, which underlies the molecular mechanism of the conditioning effect. Cyclic AMP levels in younger neurons are high but these levels decrease with age. This decrease in cAMP levels parallels the developmental loss of regenerative capacity of the neuron. In adult neurons, an elevation in cAMP results in increased growth capacity and overcomes the inhibition by MAG and myelin. Thus, manipulation of neuronal cAMP levels is likely to have significant therapeutic implications in improving nerve regeneration in the adult central nervous system (CNS) after injury.

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