GLUCOCORTICOIDS DEPRESS ACTIVITY-DEPENDENT EXPRESSION OF BDNF MESSENGER-RNA IN HIPPOCAMPAL-NEURONS

GLUCOCORTICOID hormones are important regulators of brain development and ageing, and can impair the capacity of hippocampal neurones to sur vive various neurological insults. Here we show that dexamethasone, a synthetic glucocorticoid, prevents activity-dependent increases of bra in-derived neurotrophic factor (BDNF) mRNA in cultures of rat hippocam pal neurones. In situ hybridization was used to evaluate the levels of BDNF mRNA. Up-regulation of BDNF mRNA triggered by depolarization wit h high potassium, or exposure to the glutamate receptor agonist kainic acid, resulted both from higher levels of expression in neurones and from new recruitment of cells. These data suggest that the known abili ty of glucocorticoids to exacerbate neuronal injury following ischaemi a and other metabolic insults could be due to antagonism of regulatory mechanisms governing neurotrophin levels in the brain.