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Title: ProBDNF and mature BDNF as punishment and reward signals for synapse elimination at mouse neuromuscular junctions
Authors: Shawn Je, H. 
Yang, F.
Ji, Y.
Potluri, S.
Fu, X.-Q.
Luo, Z.-G.
Nagappan, G.
Chan, J.P. 
Hempstead, B.
Son, Y.-J.
Lu, B.
Issue Date: 2013
Citation: Shawn Je, H., Yang, F., Ji, Y., Potluri, S., Fu, X.-Q., Luo, Z.-G., Nagappan, G., Chan, J.P., Hempstead, B., Son, Y.-J., Lu, B. (2013). ProBDNF and mature BDNF as punishment and reward signals for synapse elimination at mouse neuromuscular junctions. Journal of Neuroscience 33 (24) : 9957-9962. ScholarBank@NUS Repository.
Abstract: 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 (p75NTR). Furthermore, the inhibition of both p75NTR 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. © 2013 the authors.
Source Title: Journal of Neuroscience
ISSN: 02706474
DOI: 10.1523/JNEUROSCI.0163-13.2013
Appears in Collections:Staff Publications

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