Brain-derived neurotrophic factor enhances depolarization-evoked glutamate release in cultured cortical neurons.
Brain-derived neurotrophic factor (BDNF) has been reported to play an important role in neuronal plasticity. In this study, we examined the effect of BDNF on an activity-dependent synaptic function in an acute phase. First, we found that short-term treatment (10 min) with BDNF enhanced depolarization-evoked glutamate release in cultured cortical neurons. The enhancement diminished gradually according to the length of BDNF treatment. The BDNF-enhanced release did not require the synthesis of protein and mRNA. Both tetanus toxin and bafilomycin abolished the depolarization-evoked glutamate release with or without BDNF, indicating that BDNF acted via an exocytotic pathway. Next, we investigated the effect of BDNF on intracellular Ca(2+). BDNF potentiated the increase in intracellular Ca(2+) induced by depolarization. The Ca(2+) was derived from intracellular stores, because thapsigargin completely inhibited the potentiation. Furthermore, both thapsigargin and xestospongin C inhibited the effect of BDNF. These results suggested that the release of Ca(2+) from intracellular stores mediated by the IP(3) receptor was involved in the BDNF-enhanced glutamate release. Last, it was revealed that the enhancement of glutamate release by BDNF was dependent on the TrkB-PLC-gamma pathway. These results clearly demonstrate that short-term treatment with BDNF enhances an exocytotic pathway by potentiating the accumulation of intracellular Ca(2+) through intracellular stores.
Matsumoto
T
T
Division of Protein Biosynthesis, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.
Numakawa
T
T
Adachi
N
N
Yokomaku
D
D
Yamagishi
S
S
Takei
N
N
Hatanaka
H
H
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005071:Evoked Potentials / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051966:Phospholipase C gamma; D051381:Rats; D020813:Receptor, trkB / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D007527:Isoenzymes; D018698:Glutamic Acid; D020813:Receptor, trkB; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium