BRAIN-DERIVED NEUROTROPHIC FACTOR INDUCES RAPID AND TRANSIENT RELEASEOF GLUTAMATE THROUGH THE NON-EXOCYTOTIC PATHWAY FROM CORTICAL-NEURONS

There is increasing interest in the involvement of neurotrophins in ne ural transmission and plasticity. Thus, Re investigated the effects of brain-derived neurotrophic factor (BDNF) on glutamate release from co rtical neurons, Treatment of cultured cortical neurons with BDNF induc ed rapid and transient release of glutamate, This effect was suggested to be mediated by TrkB activation because R252a inhibited the release of glutamate and BDNF phosphorylated TrkB within 30 s, BDNF-induced g lutamate release was observed even when using Ca2+-free assay buffer b ut was inhibited by BAPTA-AM, a cell-permeable Ca2+ chelator, Therefor e, BDNF-induced glutamate release was independent of extracelluar Ca2 but dependent on intracellular Ca2+. Because normal neurotransmitter release is exocytotic, the involvement of the exocytotic pathway in BD NF-induced glutamate release was examined. As botulinum toxin is known to cleave exocytosis-associated proteins, thereby inhibiting exocytos is, it was applied to neurons prior to the release assay. Although bot ulinum toxin B cleaved VAMP2 and inhibited Ca2+-triggered glutamate re lease, it did not inhibit the BDNF-induced release of glutamate. These results strongly suggested that BDNF induces rapid and transient rele ase of glutamate from cortical neurons through a non-exocytotic pathwa y.