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XB-ART-38139
J Cell Sci August 1, 2008; 121 (Pt 15): 2565-77.

Enhancement of axonal regeneration by in vitro conditioning and its inhibition by cyclopentenone prostaglandins.

Tonge D , Chan K , Zhu N , Panjwani A , Arno M , Lynham S , Ward M , Snape A , Pizzey J .


Abstract
Axonal regeneration is enhanced by the prior ;conditioning'' of peripheral nerve lesions. Here we show that Xenopus dorsal root ganglia (DRG) with attached peripheral nerves (PN-DRG) can be conditioned in vitro, thereafter showing enhanced neurotrophin-induced axonal growth similar to preparations conditioned by axotomy in vivo. Actinomycin D inhibits axonal outgrowth from freshly dissected PN-DRG, but not from conditioned preparations. Synthesis of mRNAs that encode proteins necessary for axonal elongation might therefore occur during the conditioning period, a suggestion that was confirmed by oligonucleotide microarray analysis. Culturing PN-DRG in a compartmentalized system showed that inhibition of protein synthesis (but not RNA synthesis) in the distal nerve impaired the conditioning response, suggesting that changes in gene expression in cultured DRG depend on the synthesis and retrograde transport of protein(s) in peripheral nerves. The culture system was also used to demonstrate retrograde axonal transport of several proteins, including thioredoxin (Trx). Cyclopentenone prostaglandins, which react with Trx, blocked the in vitro conditioning effect, whereas inhibition of other signalling pathways thought to be involved in axonal regeneration did not. This suggests that Trx and/or other targets of these electrophilic prostaglandins regulate axonal regeneration. Consistent with this hypothesis, morpholino-induced suppression of Trx expression in dissociated DRG neurons was associated with reduced neurite outgrowth.

PubMed ID: 18650498
Article link: J Cell Sci
Grant support: [+]
Genes referenced: abcb1 ackr3 aire arg1 atf3 aurkb basp1 bdnf camk2a ccnb1.2 cebpb cnn1 cuedc2 dpepe drg1 eif4a1 erg fcn1 furin gap43 gata2 gstp1 h2bc14 igf2 igf2bp3 inhbc.1 itga7 jak2 jun lgals1.1 lmnb1 loc100170420 mad2l1 mapk8 mcm4 mt4 ncaph nhlh1 npm3 ntf3 ntf4 ntrk1 pax2 prdm1 prkca prkcg pxn ras-dva1 rhoq s100a10 sfrp1 sox7 stat3.1 tnfrsf12a tnpo1 txn vim
Morpholinos: txn MO1


Article Images: [+] show captions


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