title: Synapsins Are Downstream Players of the BDNF-Mediated Axonal Growth.
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 p75NTRassociated 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/p75NTRimbalance. The data indicate that Syn I plays a pivotal role in the BDNF signal transduction during axonal growth.
authors.affiliation: Department of Experimental Medicine, University of Genova, Viale Benedetto XV 3, 16132, Genova, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Marte
authors.affiliation: 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.
authors.forename: Mirko
authors.initials: M
authors.lastname: Messa
authors.affiliation: Department of Experimental Medicine, University of Genova, Viale Benedetto XV 3, 16132, Genova, Italy.|Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Via Morego 30, 16163, Genova, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Benfenati
authors.affiliation: Department of Experimental Medicine, University of Genova, Viale Benedetto XV 3, 16132, Genova, Italy. franco.onofri@unige.it.
authors.forename: Franco
authors.initials: F
authors.lastname: Onofri
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D049108:Cell Enlargement / Q000187:drug effects; D002478:Cells, Cultured; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016704:Synapsins / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016704:Synapsins
keywords: BDNF; Neuronal development; Neurotrophin; Synapsin; TrkB; p75NTR