ProBDNF and Mature BDNF as Punishment and Reward Signals for Synapse Elimination at Mouse Neuromuscular Junctions
| Autor: | Zhen-Ge Luo, Feng Yang, Yuanyuan Ji, Young-Jin Son, Xiu-Qing Fu, Bai Lu, S. Potluri, Barbara L. Hempstead, J. P. Chan, G. Nagappan, Hyunsoo Shawn Je |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Neuromuscular Junction Presynaptic Terminals Mice Transgenic Nerve Tissue Proteins Receptors Nerve Growth Factor Biology Neuromuscular junction Synapse Mice Neurotrophic factors Postsynaptic potential medicine Animals Receptor trkB Low-affinity nerve growth factor receptor Protein Precursors Axon Protein Kinase Inhibitors Neurons Brain-derived neurotrophic factor Analysis of Variance Brain-Derived Neurotrophic Factor General Neuroscience Gene Expression Regulation Developmental Axons Mice Inbred C57BL Pyrimidines medicine.anatomical_structure Animals Newborn Spinal Cord nervous system Pyrazoles Female Signal transduction Brief Communications Neuroscience Signal Transduction |
| Zdroj: | Journal of Neuroscience. 33:9957-9962 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | During development, mammalian neuromuscular junctions (NMJs) transit from multiple-innervation to single-innervation through axonal competition via unknown molecular mechanisms. Previously, using an in vitro model system, we demonstrated that the postsynaptic secretion of pro-brain-derived neurotrophic factor (proBDNF) stabilizes or eliminates presynaptic axon terminals, depending on its proteolytic conversion at synapses. Here, using developing mouse NMJs, we obtained in vivo evidence that proBDNF and mature BDNF (mBDNF) play roles in synapse elimination. We observed that exogenous proBDNF promoted synapse elimination, whereas mBDNF infusion substantially delayed synapse elimination. In addition, pharmacological inhibition of the proteolytic conversion of proBDNF to mBDNF accelerated synapse elimination via activation of p75 neurotrophin receptor (p75(NTR)). Furthermore, the inhibition of both p75(NTR) and sortilin signaling attenuated synapse elimination. We propose a model in which proBDNF and mBDNF serve as potential "punishment" and "reward" signals for inactive and active terminals, respectively, in vivo. |
| Databáze: | OpenAIRE |
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