BRAIN INSULTS IN RATS INDUCE INCREASED EXPRESSION OF THE BDNF GENE THROUGH DIFFERENTIAL USE OF MULTIPLE PROMOTERS

The rat brain-derived neurotrophic factor (BDNF) gene consists of four short 5'-exons linked to separate promoters and one 3'-exon encoding the mature BDNF protein. Using in situ hybridization we demonstrate he re that kindling-induced seizures, cerebral ischaemia and insulin-indu ced hypoglycaemic coma increase BDNF mRNA levels through insult- and r egion-specific usage of three promoters within the BDNF gene. Both bri ef (2 min) and longer (10 min) periods of forebrain ischaemia induced significant and major increases only of exon III mRNA in the dentate g yrus. Following hypoglycaemic coma (1 and 30 min), exon III mRNA was m arkedly elevated in the dentate gyrus and, in addition, exon I mRNA sh owed a moderate increase. Single and recurrent (n = 40) hippocampal se izures significantly increased expression of exon I, II and III mRNAs in the dentate gyrus granule cells. After recurrent seizures, includin g generalized convulsions, there were also major increases of both exo n I and III mRNAs in the CA3 region, amygdala, piriform cortex and neo cortex, whereas in the hippocampal CA1 sector marked elevations were d etected only for exon III mRNA. The insults had no effect on the level of exon IV mRNA in the brain. The region- and insult-specific pattern of promoter activation might be of importance for the effectiveness o f protective responses as well as for the regulation of plastic change s following brain insults.