title: Axotomy induces axonogenesis in hippocampal neurons through STAT3.
abstract: After axotomy of embryonic hippocampal neurons in vitro, some of the axotomized axons lose their identity, and new axons arise and grow. This axotomy-induced axonogenesis requires importin, suggesting that some injury-induced signals are transported via axons to elicit axonogenesis after axotomy. In this study, we show that STAT3 is activated in response to axotomy. Because STAT3 was co-immunoprecipitated with importin β in the axotomized neurons, we suggest that STAT3 is retrogradely transported as molecular cargo of importin α/β heterodimers. Indeed, inhibition of importin α binding with STAT3 resulted in the attenuation of axonogenesis. Silencing STAT3 blocked the axonogenesis, demonstrating that STAT3 is necessary for axotomy-induced axonogenesis. Furthermore, the overexpression of STAT3 enhanced axotomy-induced axonogenesis. Taken together, these results demonstrate that activation and retrograde transport of STAT3 in injured axons have key roles in the axotomy-induced axonogenesis of hippocampal neurons.
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Ohara
authors.forename: Y
authors.initials: Y
authors.lastname: Fujita
authors.forename: K
authors.initials: K
authors.lastname: Hata
authors.forename: M
authors.initials: M
authors.lastname: Nakagawa
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D019771:Axotomy; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat