Acute and gradual increases in BDNF concentration elicit distinct signaling and functions in neurons.
Extracellular factors may act on cells in two distinct modes: an acute increase in concentration as a result of regulated secretion, or a gradual increase in concentration when secreted constitutively or from a distant source. We found that cellular responses to brain-derived neurotrophic factor (BDNF) differed markedly depending on how BDNF was delivered. In cultured rat hippocampal neurons, acute and gradual increases in BDNF elicited transient and sustained activation of TrkB receptor and its downstream signaling, respectively, leading to differential expression of Homer1 and Arc. Transient TrkB activation promoted neurite elongation and spine head enlargement, whereas sustained TrkB activation facilitated neurite branch and spine neck elongation. In hippocampal slices, fast and slow increases in BDNF enhanced basal synaptic transmission and LTP, respectively. Thus, the kinetics of TrkB activation is critical for cell signaling and functions. This temporal dimension in cellular signaling may also have implications for the therapeutic drug design.
Ji
Yuanyuan
Y
Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
Lu
Yuan
Y
Yang
Feng
F
Shen
Wanhua
W
Tang
Tina Tze-Tsang
TT
Feng
Linyin
L
Duan
Shumin
S
Lu
Bai
B
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D049229:Dendritic Spines / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D000072233:Homer Scaffolding Proteins; D066298:In Vitro Techniques; D007700:Kinetics; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051381:Rats; D020813:Receptor, trkB / Q000378:metabolism*; D015398:Signal Transduction; D009435:Synaptic Transmission / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C000606614:HOMER1 protein, human; D000072233:Homer Scaffolding Proteins; C000606623:Homer1 protein, mouse; C000606624:Homer1 protein, rat; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein; D020813:Receptor, trkB