NGF HAS OPPOSING EFFECTS ON NA-III AND SNS GENE-EXPRESSION IN SPINAL SENSORY NEURONS( CHANNEL)

FOLLOWING sciatic nerve transection, the expression of sodium channel III (alpha-III) transcripts increases and SNS (alpha-SNS) transcripts decreases in small (<25 mu m diameter) dorsal root ganglion (DRG) neur ons, which may reflect an interruption of retrograde transport of peri pherally derived factor(s) involved in the regulation of these channel s. To test the hypothesis that the neurotrophin nerve growth factor (N GF), which is abundant in peripheral targets, participates in the modu lation of the expression of these sodium channel transcripts, we exami ned the hybridization signal of alpha-SNS and alpha-III mRNAs in small DRG neurons from adult rats that had been dissociated and maintained for 7 days in the absence or presence of exogenous NGF. Neurons mainta ined in control (no added NGF) cultures showed changes in alpha-III an d alpha-SNS hybridization signal similar to those induced by axotomy, with increased alpha-III mRNA levels and decreased alpha-SNS mRNA leve ls, compared with those observed in small DRG neurons at 1 day in vitr o. The addition of exogenous NGF to DRG cultures attenuated these alte rations in transcript levels, decreasing alpha-III mRNA and increasing alpha-SNS mRNA expression. These results suggest that NGF participate s in the regulation of membrane excitability in small DRG neurons by p athways that include opposing effects on different sodium channel gene s.