Differential regulation of multiple brain-derived neurotrophic factor transcripts in the postnatal and adult rat hippocampus during development, and in response to kainate administration

Abstract

Brain-derived neurotrophic factor (BDNF) is expressed at high levels in the hippocampus, where it has been implicated in physiological functions such as the modulation of synaptic strength as well as in the pathophysiology of epileptic seizures. BDNF expression is highly regulated and the BDNF gene can generate multiple transcript isoforms by alternate splicing of four 5' exons (exons I-IV) to one 3' exon (exon V). To gain insight into the regulation of different BDNF transcripts in specific hippocampal subfields during postnatal development, exon-specific riboprobes were used. Our data shows that BDNF exon I and exon II mRNAs are regulated in hippocampal subfields during postnatal development, in contrast to BDNF exon III and exon IV mRNA, which remain relatively stable through this period. Further, exons I and II show distinct temporal patterns of expression in the hippocampus: BDNF I mRNA peaks in adulthood in contrast to BDNF II mRNA which peaks at postnatal day 14 (P14). Finally, we have addressed whether kainate treatment in postnatal pups and adults regulates BDNF through the recruitment of the same, or distinct, BDNF promoters. Our data indicates that kainate-induced seizures induce strikingly different expression of distinct BDNF transcripts, both in magnitude as well as spatial patterns in the hippocampal subfields, of pups as compared to adults. These results suggest that kainate-mediated seizures differentially recruit BDNF promoters in the developing postnatal hippocampus in contrast to the adult hippocampus to achieve a hippocampal subfield specific regulation of exon-specific BDNF mRNAs.