COMPARISON OF CHANGES IN BETA-TUBULIN AND NF GENE-EXPRESSION IN RAT DRG NEURONS UNDER REGENERATION-PERMISSIVE AND REGENERATION-PROHIBITIVE CONDITIONS

To examine the question of whether or not prevention of axonal regrowt h after injury affects the molecular responses of neurons to axotomy, Northern blotting and in situ hybridization were used to study changes in the mRNA levels of neurofilament (NF) proteins and tubulins in rat dorsal root ganglion (DRG) cells. Adult male rats sustained either a crush lesion of the mid-sciatic nerve (regeneration-permissive conditi on) or a cut lesion of the sciatic nerve combined with ligation of the proximal nerve stump and removal of a large segment of the distal ner ve (regeneration-prohibitive condition). At 14 days post-injury, the r elative levels of the low (NF-L) and middle (NF-M) molecular weight NF protein mRNAs, as well as those of beta(II)- and beta(III)-tubulin, w ere examined in the L4 and L5 DRG. The data showed that the levels of NF-L and NF-M mRNAs decreased while beta-(II) and beta(III)-tubulin mR NA levels increased in the DRG after either crush axotomy or cut/ligat ion axotomy of the sciatic nerve, suggesting that the elicitation of t hese molecular changes by axon disconnection is independent of the ult imate success or failure of the axonal regrowth process. However, cut/ ligation axotomy had a more pronounced effect than did crush injury on the mRNA changes. This result suggests that feedback mechanisms from regrowing axons are important in regulating the extent of the cytoskel etal mRNA changes in injured neurons.