LIMBIC SEIZURES INDUCE A DIFFERENTIAL REGULATION OF THE EXPRESSION OF NERVE GROWTH-FACTOR, BRAIN-DERIVED NEUROTROPHIC FACTOR AND NEUROTROPHIN-3, IN THE RAT HIPPOCAMPUS

Small unilateral electrolytic lesions placed in the hilus of the dentate gyrus produce limbic seizures. We have investigated the effects of these hilar lesions on the levels of the mRNAs encoding for 3 neurotrophic factors (NTF): nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3). 'In situ' hybridization histochemistry with synthetic oligonucleotides was used to analyze their mRNA distribution and levels. In agreement with previously published data (Science, 245 (1989) 758-761), NGF mRNA was found bilaterally, quickly and transiently increased in granule cells of the dentate gyrus. Only 2 h after the onset of limbic seizures, mRNA levels for BDNF were also found to be dramatically elevated in both sides of the hippocampus, reaching a maximum 30-fold increase in the granule cell layer of the dentate gyrus 5 h after the lesion. Moreover, increased levels of this mRNA were also been found in the pyramidal layer of the CA3 (5-fold) and CA1 (15-fold) hippocampal fields. In contrast, NT3 mRNA was found to be clearly and bilaterally decreased in dentate gyrus granule cells, reaching 5- to 6-fold decreased levels at 12 h lesion. Taken together, these results clearly show a different regulation of neurotrophic factors genes (NGF, BDNF and NT3) expression in the different hippocampal fields, as a consequence of seizure-producing hilar lesions.