Brain-derived neurotrophic factor-induced potentiation of glutamate and GABA release: different dependency on signaling pathways and neuronal activity.
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. BDNF-potentiated 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. Chem. 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.
Matsumoto
Tomoya
T
Neuronics Research Group, Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Osaka 563-8577, Japan.
Numakawa
Tadahiro
T
Yokomaku
Daisaku
D
Adachi
Naoki
N
Yamagishi
Satoru
S
Numakawa
Yumiko
Y
Kunugi
Hiroshi
H
Taguchi
Takahisa
T
D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid