PMID- 12196581 OWN - NLM STAT- MEDLINE DCOM- 20020913 LR - 20220408 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 22 IP - 17 DP - 2002 Sep 1 TI - Brain-derived neurotrophic factor promotes the maturation of GABAergic mechanisms in cultured hippocampal neurons. PG - 7580-5 AB - Brain-derived neurotrophic factor (BDNF) has been implicated in activity-dependent plasticity of neuronal function and network arrangement. To clarify how BDNF exerts its action, we evaluated the physiological, histological, and biochemical characteristics of cultured hippocampal neurons after long-term treatment with BDNF. Here we show that BDNF facilitates high K(+)-elicited release of GABA but not of glutamate and induces an increase in immunoreactive signals of glutamic acid decarboxylase, a GABA-synthesizing enzyme. The soma size of GABAergic neurons was enlarged in BDNF-treated cultures, whereas the average soma size of all neurons was virtually unchanged. BDNF also upregulated protein levels of GABA(A) receptors but not of glutamate receptors. These data imply that BDNF selectively advances the maturation of GABAergic synapses. However, immunocytochemical analyses revealed that a significant expression of TrkB, a high-affinity receptor for BDNF, was detected in non-GABAergic as well as GABAergic neurons. BDNF also increased to total amount of synaptic vesicle-associated proteins without affecting the number of presynaptic vesicles that can be labeled with FM1-43 after K(+) depolarization. Together, our findings indicate that BDNF principally promotes GABAergic maturation but may also potentially contribute to excitatory synapse development via increasing resting synaptic vesicles. FAU - Yamada, Maki K AU - Yamada MK AD - Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. maki@mol.f.u-tokyo.ac.jp FAU - Nakanishi, Kohsuke AU - Nakanishi K FAU - Ohba, Shizu AU - Ohba S FAU - Nakamura, Takeshi AU - Nakamura T FAU - Ikegaya, Yuji AU - Ikegaya Y FAU - Nishiyama, Nobuyoshi AU - Nishiyama N FAU - Matsuki, Norio AU - Matsuki N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (FM1 43) RN - 0 (Fluorescent Dyes) RN - 0 (Membrane Proteins) RN - 0 (Pyridinium Compounds) RN - 0 (Quaternary Ammonium Compounds) RN - 0 (R-SNARE Proteins) RN - 0 (Receptors, GABA-A) RN - 0 (Receptors, Glutamate) RN - 0 (Synapsins) RN - 0 (Synaptophysin) RN - 3KX376GY7L (Glutamic Acid) RN - 56-12-2 (gamma-Aminobutyric Acid) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 4.1.1.15 (Glutamate Decarboxylase) RN - RWP5GA015D (Potassium) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cell Differentiation/drug effects/physiology MH - Cell Size/drug effects MH - Cells, Cultured MH - Fluorescent Dyes MH - Glutamate Decarboxylase/biosynthesis MH - Glutamic Acid/metabolism MH - Hippocampus/cytology/*drug effects/metabolism MH - Immunohistochemistry MH - Membrane Proteins/metabolism MH - Neurons/cytology/*drug effects/metabolism MH - Potassium/pharmacology MH - Pyridinium Compounds MH - Quaternary Ammonium Compounds MH - R-SNARE Proteins MH - Rats MH - Rats, Wistar MH - Receptor, trkB/metabolism MH - Receptors, GABA-A/metabolism MH - Receptors, Glutamate/metabolism MH - Synapses/drug effects/metabolism MH - Synapsins/metabolism MH - Synaptic Vesicles/drug effects/metabolism MH - Synaptophysin/metabolism MH - gamma-Aminobutyric Acid/*metabolism PMC - PMC6757965 EDAT- 2002/08/28 10:00 MHDA- 2002/09/14 10:01 PMCR- 2003/03/01 CRDT- 2002/08/28 10:00 PHST- 2002/08/28 10:00 [pubmed] PHST- 2002/09/14 10:01 [medline] PHST- 2002/08/28 10:00 [entrez] PHST- 2003/03/01 00:00 [pmc-release] AID - 22/17/7580 [pii] AID - 6713 [pii] AID - 10.1523/JNEUROSCI.22-17-07580.2002 [doi] PST - ppublish SO - J Neurosci. 2002 Sep 1;22(17):7580-5. doi: 10.1523/JNEUROSCI.22-17-07580.2002.