Possible involvement of BDNF release in long-lasting synapse formation induced by repetitive PKA activation.
For the analysis of the cellular mechanism underlying long-term synaptic plasticity, a model system that allows long-lasting pursuit is required. Previously we reported that, in hippocampal neurons under dissociated cell culture conditions, repeated (but not a single) transient activation of protein kinase A (PKA) led to an increase in the number of synapses that lasted >3 weeks, and hence we proposed that this phenomenon should serve as an appropriate model system. Here we report that repeated pulsatile application of brain-derived neurotrophic factor (BDNF) leads to persistent synapse formation equivalent to that after the repeated transient activation of PKA. A BDNF-scavenging substance applied concomitantly with PKA activation abolished the synapse formation. The release of BDNF upon PKA activation was confirmed by phosphorylation of TrkB. These results indicate that the release of BDNF is involved in the putative signaling cascade connecting PKA activation and synapse formation.
Taniguchi
Naoko
N
Department of Neuroscience, Osaka University Graduate School of Frontier Biosciences, Machikaneyama-cho 1-1, Toyonaka, Osaka 560-0043, Japan.
Shinoda
Yo
Y
Takei
Nobuyuki
N
Nawa
Hiroyuki
H
Ogura
Akihiko
A
Tominaga-Yoshino
Keiko
K
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D016708:Synaptophysin / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016708:Synaptophysin; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP; D020813:Receptor, trkB; D017868:Cyclic AMP-Dependent Protein Kinases