Activity-induced
brain-derived neurotrophic factor (
BDNF) expression is negatively modulated by circulating adrenal
steroids. The rat
BDNF gene gives rise to four major transcript forms that each contain a unique 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
adrenalectomy has differential effects on basal and activity-induced
BDNF transcript expression in hippocampus.
Adrenalectomy alone had only modest effects on
BDNF mRNA levels with slight increases in exon III-containing
mRNA with 7-10-day survival and in exon II-containing
mRNA with 30-days survival. In the dentate gyrus granule cells,
adrenalectomy markedly potentiated increases in exon I and II
cRNA labeling, but not increases in exon III and IV
cRNA labeling, elicited by one hippocampal afterdischarge. 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 (ADX) 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 demonstrate that the negative effects of adrenal
hormones on activity-induced
BDNF expression are by far the greatest for transcripts containing exons I and II. Together with evidence for region-specific transcript expression, these results suggest that the effects of stress on adaptive changes in
BDNF signalling will be greatest for neurons that predominantly express transcripts I and II.