CHANGE IN NEUROTROPHINS AND THEIR RECEPTOR MESSENGER-RNAS IN THE RAT FOREBRAIN AFTER STATUS EPILEPTICUS INDUCED BY PILOCARPINE

We studied the effects of status epilepticus (SE) induced by lithium c hloride/pilocarpine treatment on gene expression of neurotrophins of t he nerve growth factor (NGF) family and of their high-affinity recepto rs of the tyrosine protein kinase (trk) family in the forebrain. Using in situ hybridization (ISH), we demonstrated an early (3 h after trea tment) increase in brain-derived neurotrophic factor (BDNF) and trkB m RNA expression in the dentate gyrus, amygdala, and piriform cortex, as well as widespread increases in the cerebral cortex. NGF mRNA, but no t the mRNA of its receptor trkA, was increased in the dentate gyrus. I n contrast, 12 h after treatment, neurotrophin-3 (NT-3) decreased, and its receptor trkC mRNA increased. There was no change in NT-4 mRNA le vels. All changes were blocked by pretreatment with scopolamine, a mus carinic antagonist. The noncompetitive N-methyl-D-aspartate (NMDA) ant agonist ketamine blocked NGF, BDNF, and trkB mRNA increases in the hip pocampus and cerebral cortex, but not in the amygdala and piriform cor tex. In contrast, ketamine did not affect NT-3 and trkC changes. These results provide a complete description of changes in mRNA levels of n eurotrophins and their receptors in the forebrain after SE and supply additional data supporting the view that neurotrophin gene expression is related to abnormal neuronal activity.