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Synapsins Are Downstream Players of the BDNF-Mediated Axonal Growth

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Abstract

Synapsins (Syns) are synaptic vesicle-associated phosphoproteins involved in neuronal development and neurotransmitter release. While Syns are implicated in the regulation of brain-derived neurotrophic factor (BDNF)-induced neurotransmitter release, their role in the BDNF developmental effects has not been fully elucidated. By using primary cortical neurons from Syn I knockout (KO) and Syn I/II/III KO mice, we studied the effects of BDNF and nerve growth factor (NGF) on axonal growth. While NGF had similar effects in all genotypes, BDNF induced significant differences in Syn KO axonal outgrowth compared to wild type (WT), an effect that was rescued by the re-expression of Syn I. Moreover, the significant increase of axonal branching induced by BDNF in WT neurons was not detectable in Syn KO neurons. The expression analysis of BDNF receptors in Syn KO neurons revealed a significant decrease of the full length TrkB receptor and an increase in the levels of the truncated TrkB.t1 isoform and p75NTR associated with a marked reduction of the BDNF-induced MAPK/Erk activation. By using the Trk inhibitor K252a, we demonstrated that these differences in BDNF effects were dependent on a TrkB/p75NTR imbalance. The data indicate that Syn I plays a pivotal role in the BDNF signal transduction during axonal growth.

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Acknowledgments

This work was supported by research grants from the Italian Ministry of University and Research (PRIN 2010–2011 to F.O. and F.B.). We thank Drs. Hung-Teh Kao (Brown University, Providence, RI) and Paul Greengard (The Rockefeller University, New York City, NY) for providing us with the synapsin KO mutant mice and Dr. Silvia Casagrande for the preparation of primary cultures of cortical neurons.

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Authors and Affiliations

  1. Department of Experimental Medicine, University of Genova, Viale Benedetto XV 3, 16132, Genova, Italy

    Antonella Marte, Fabio Benfenati & Franco Onofri

  2. Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, 06519, New Haven, CT, USA

    Mirko Messa

  3. Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Via Morego 30, 16163, Genova, Italy

    Fabio Benfenati

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  1. Antonella Marte
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Correspondence to Franco Onofri.

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Marte, A., Messa, M., Benfenati, F. et al. Synapsins Are Downstream Players of the BDNF-Mediated Axonal Growth. Mol Neurobiol 54, 484–494 (2017). https://doi.org/10.1007/s12035-015-9659-3

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