Differential usage of multiple brain-derived neurotrophic factor promoter in rat dorsal root ganglia following peripheral nerve injuries and inflammation.
The brain-derived neurotrophic factor (BDNF) may act as either an autocrine or paracrine survival factor for the dorsal root ganglion (DRG) neurons and may also serve as a neurotransmitter or neuromodulator within the dorsal horn of the spinal cord. The rat BDNF gene consists of four short 5' exons linked to separate promoters and one 3' exon encoding the mature BDNF protein. An exon-specific reverse transcription-polymerase chain reaction analysis was used to study the differential utilization of multiple promoters in the DRG following unilateral sciatic axotomy, dorsal rhizotomy and peripheral inflammation. The exon I transcript showed the highest induction rate with the ipsilateral expression elevated 4.3-5.8 times that of contralateral expression. Both exon II and III mRNAs showed a smaller increase 1 day after the three kinds of stimuli. In addition, exon IV mRNA transcription increased slightly only after rhizotomy, but not after axotomy and peripheral inflammation after 1 day. Furthermore, the elevated exon I mRNA levels 1 day after rhizotomy were sustained for up to 7 days. In contrast, those of the exon I mRNA after axotomy had declined 2.8 times the control level after 7 days. These findings suggest that the promoter linked to exon I may provide a major regulatory point of BDNF mRNA expression by peripheral nerve injuries and inflammation. In addition, both exon I and IV mRNA expression may show different temporal activation patterns according to the types of injury.