TRANSCRIPT-SPECIFIC EFFECTS OF ADRENALECTOMY ON SEIZURE-INDUCED BDNF EXPRESSION IN RAT HIPPOCAMPUS

Activity-induced brain-derived neurotrophic factor (BDNF) expression i s negatively modulated by circulating adrenal steroids. The rat BDNF g ene gives rise to four major transcript forms that each contain a uniq ue 5' exon (I-IV) and a common 3' exon (V) that codes for BDNF protein . Exon-specific in situ hybridization was used to determine if adrenal ectomy has differential effects on basal and activity-induced BDNF tra nscript expression in hippocampus. Adrenalectomy alone had only modest effects on BDNF mRNA levels with slight increases in exon III-contain ing mRNA with 7-10-day survival and in exon II-containing mRNA with 30 -day survival. In the dentate gyrus granule cells, adrenalectomy marke dly potentiated increases in exon I and II cRNA labeling, but not incr eases in exon III and IV cRNA labeling, elicited by one hippocampal af terdischarge. Similarly, for the granule cells and CA1 pyramidal cells , hilus lesion (HL)-induced recurrent limbic seizures elicited greater increases in exon I and II cRNA hybridization in adrenalectomized (AD X) as compared to adrenal-intact rats. In this paradigm, adrenalectomy modestly potentiated the increase in exon III-containing mRNA in CA1 but had no effect on exon IV-containing mRNA content. These results de monstrate that the negative effects of adrenal hormones on activity-in duced BDNF expression are by far the greatest for transcripts containi ng exons I and II. Together with evidence for region-specific transcri pt expression, these results suggest that the effects of stress on ada ptive changes in BDNF signalling will be greatest for neurons that pre dominantly express transcripts I and II. (C) 1998 Elsevier Science B.V .