Brain-derived neurotrophic factor promotes the maturation of GABAergic mechanisms in cultured hippocampal neurons.
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.
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
Maki K
MK
Yamada
Kohsuke
K
Nakanishi
Shizu
S
Ohba
Takeshi
T
Nakamura
Yuji
Y
Ikegaya
Nobuyoshi
N
Nishiyama
Norio
N
Matsuki
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D005456:Fluorescent Dyes; D005968:Glutamate Decarboxylase / Q000096:biosynthesis; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D050683:R-SNARE Proteins; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D016704:Synapsins / Q000378:metabolism; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; C073804:FM1 43; D005456:Fluorescent Dyes; D008565:Membrane Proteins; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D050683:R-SNARE Proteins; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D016704:Synapsins; D016708:Synaptophysin; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D020813:Receptor, trkB; D005968:Glutamate Decarboxylase; D011188:Potassium