Sciatic nerve transection evokes lasting up-regulation of angiotensin AT 2 and AT 1 receptor mRNA in adult rat dorsal root ganglia and sciatic nerves

Abstract

The angiotensin AT 2 receptor is involved in tissue repair and cellular stress responses in non-neuronal cells. We have previously observed that the AT 2 receptor-induced neurite formation in PC12W cells is paralleled by a reduced neurofilament M expression as it occurs in nerve fiber regeneration. Here we show that transection and crush of sciatic nerve fibers of adult rats results in dramatic changes of AT 2, AT 1a and AT 1b receptor mRNA in dorsal root ganglion neurons (DRGs) and in sciatic nerves 3, 14 and 28 days after axotomy and crush. The expression patterns were determined by reverse transcription polymerase chain reaction (RT-PCR) assay, and the specificity of amplification products was verified by Southern blot hybridization. Whereas axotomy evoked a transient increase of AT 2 receptor mRNA by more than 1000% after 3 days in proximal and after 14 days in distal sciatic nerve stumps (510%), the maximum expression in DRGs was observed after 14 days (1100%). Sciatic nerve crush resulted in a time-dependent up-regulation of AT 2 receptor mRNA in sciatic nerve segments coinciding with the successful regeneration of nerve fibers. In sciatic nerves, AT 1a and AT 1b receptor mRNA levels were increased within different time-courses and to different extents with a maximum expression of 570%. In contrast to AT 1a receptor mRNAs, AT 1b receptor mRNA levels were increased in DRGs by maximally 800%. These results suggest that AT 2 and AT 1 receptor-mediated pathways are involved in Schwann cell-mediated myelination and in neuroregenerative responses of DRGs.