ATF3 Increases the Intrinsic Growth State of DRG Neurons to Enhance Peripheral Nerve Regeneration

We have examined which transcription factors activated by peripheral axonal injury may mediate the conditioning effect by regulating expression of effectors that increase the intrinsic growth state of the neurons

R. Seijffers

2007

Scholarcy highlights

  • Peripheral nerve regeneration involves cytoskeletal protein assembly, formation of new membrane and expression of multiple adhesion molecules and receptors at growth cones
  • We have examined which transcription factors activated by peripheral axonal injury may mediate the conditioning effect by regulating expression of effectors that increase the intrinsic growth state of the neurons
  • Activating transcription factor 3 increased dorsal root ganglion neurite elongation when cultured on permissive substrates but did not overcome the inhibitory effects of myelin or promote central axonal regeneration in the spinal cord in vivo
  • Mouse ATF3 cDNA and the human placental alkaline phosphatase reporter were cloned as a bicistronic expression cassette into the thy1.2 expression vector
  • We hypothesized that ATF3 contributes to nerve regeneration by coordinating expression of growth-associated genes, both because it is the only known transcription factor induced in all injured DRG neurons after a peripheral but not central axonal injury, and because it enhances neurite outgrowth in culture
  • We show that ATF3 does enhance the rate of regeneration in the PNS to an extent similar to wt mice preconditioned by a nerve injury
  • In addition to its role as a survival factor, Hsp27 enhances neurite outgrowth in cultured adult dorsal root ganglion neurons, possibly as a result of interactions with the cytoskeleton, and may contribute to the enhanced peripheral nerve regeneration in the transgenic mice

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