NMDA-STIMULATED EXPRESSION OF BDNF MESSENGER-RNA IN CULTURED CEREBELLAR GRANULE NEURONS

THE brain-derived neurotrophic factor (BDNF) affects the developing ce rebellar granule cells. Exposure of 9-11-day-old primary cultures of r at cerebellar granule neurones for 3 h to a more depolarizing medium ( additional 15-30 mM KCl) stimulated the release of glutamate and incre ased the BDNF mRNAs levels. This BDNF and mRNA upregulation was inhibi ted by dizocilpine (MK-801), the noncompetitive blocker of N-methyl-D- aspartate (NMDA)-sensitive glutamate receptors, and mimicked by NMDA. Continuous (up to 5 h) culture exposure to non-toxic NMDA concentratio n resulted in a prolonged increase in BDNF mRNA expression and enhance d neuronal resistance to glutamate toxicity. The latter effect of NMDA was attenuated by cycloheximide, a protein synthesis inhibitor. The m echanisms responsible for NMDA-triggered BDNF upregulation and neuropr otection might be important in the compensatory response of brain to e xcitotoxicity.