The mechanisms underlying BDNF-modulated neurotransmitter release remain elusive. Here, we found that 24-h exposure of postnatal cortical neurons to BDNF potentiated depolarization-evoked glutamate and GABA release in a protein synthesis-dependent manner. BDNFpotentiated glutamate release occurred through the PLC-gamma and MAPK pathways. The expression of synapsin I, synaptotagmin, and synaptophysin, but not of syntaxin or SNAP25, increased through the PLC-gamma and MAPK pathways. In contrast, BDNF-up-regulated GABA release and GAD65/67 expression depended on MAPK. Furthermore, neuronal activity was necessary for the up-regulation of glutamate release and synapsin I, synaptotagmin, and synaptophysin expression, but not of GABA or GAD65/67. PLC-gamma inhibitor attenuated BDNF-stimulated long-lasting MAPK activation. As BDNF rapidly potentiates glutamatergic transmission through PLC-gamma (J. BioL Client. 277, (2002) 6520-6529), PLC-gamma-mediated neuronal activity might sustain MAPK activation, resulting in BDNF-potentiated glutamate release. In conclusion, BDNF potentiates the excitatory and inhibitory system separately, which may be important for the regulation of synaptic plasticity. (C) 2005 Elsevier Inc. All rights reserved.
机构:Univ Buenos Aires, Fac Med, Inst Biol Cellular & Neurociencias, RA-1121 Buenos Aires, DF, Argentina
Alonso, M
Medina, JH
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机构:Univ Buenos Aires, Fac Med, Inst Biol Cellular & Neurociencias, RA-1121 Buenos Aires, DF, Argentina
Medina, JH
Pozzo-Miller, L
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Univ Buenos Aires, Fac Med, Inst Biol Cellular & Neurociencias, RA-1121 Buenos Aires, DF, ArgentinaUniv Buenos Aires, Fac Med, Inst Biol Cellular & Neurociencias, RA-1121 Buenos Aires, DF, Argentina
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Univ Calif San Francisco, Dept Pathol, Vet Adm Med Ctr, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Pathol, Vet Adm Med Ctr, San Francisco, CA 94143 USA
Huang, EJ
Reichardt, LF
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机构:Univ Calif San Francisco, Dept Pathol, Vet Adm Med Ctr, San Francisco, CA 94143 USA
机构:Univ Buenos Aires, Fac Med, Inst Biol Cellular & Neurociencias, RA-1121 Buenos Aires, DF, Argentina
Alonso, M
Medina, JH
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机构:Univ Buenos Aires, Fac Med, Inst Biol Cellular & Neurociencias, RA-1121 Buenos Aires, DF, Argentina
Medina, JH
Pozzo-Miller, L
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Univ Buenos Aires, Fac Med, Inst Biol Cellular & Neurociencias, RA-1121 Buenos Aires, DF, ArgentinaUniv Buenos Aires, Fac Med, Inst Biol Cellular & Neurociencias, RA-1121 Buenos Aires, DF, Argentina
机构:
Univ Calif San Francisco, Dept Pathol, Vet Adm Med Ctr, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Pathol, Vet Adm Med Ctr, San Francisco, CA 94143 USA
Huang, EJ
Reichardt, LF
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h-index: 0
机构:Univ Calif San Francisco, Dept Pathol, Vet Adm Med Ctr, San Francisco, CA 94143 USA