Sphingosine 1-Phosphate Receptor 1 Modulates CNTF-Induced Axonal Growth and Neuroprotection in the Mouse Visual System

Abstract : The lack of axonal regeneration and neuronal cell death causes permanent neurological deficits in the injured CNS. Using the classical CNS injury model of optic nerve crush in mice, ciliary neurotrophic factor (CNTF) was found to stimulate retinal ganglion cell (RGC) survival and axonal growth, but in an incomplete fashion. The elucidation of molecular mechanisms impairing CNTF-induced axonal regeneration is paramount to promote visual recovery. In the present study, we sought to evaluate the contribution of sphingosine 1-phosphate receptor 1 (S1PR1) to the neuroprotective and regenerative effects of CNTF. The transduction of retinal cells with adeno-associated viruses (AAV) allowed to activate CNTF/signal transducer and activator of transcription 3 (Stat3) signaling and to modulate S1PR1 expression in RGCs. Our results showed that CNTF/Stat3 prevented injury-induced S1PR1 downregulation. Silencing S1PR1 in RGCs significantly enhanced CNTF-induced axonal growth in the injured optic nerve. In contrast, RGC survival was markedly decreased when S1PR1 was repressed with viral vectors. The level of phosphorylated Stat3 (P-Stat3), an intracellular mediator of CNTF, did not fluctuate after S1PR1 inhibition and CNTF stimulation. Collectively, these results suggest that S1PR1 acts as a major regulator of retinal neuron survival and restricts the RGC growth response induced by CNTF.
Type de document :
Article dans une revue
Neural plasticity, Hymie Anisman, 2017, pp.6818970. 〈10.1155/2017/6818970〉
Liste complète des métadonnées

Littérature citée [61 références]  Voir  Masquer  Télécharger

http://hal.upmc.fr/hal-01654649
Contributeur : Gestionnaire Hal-Upmc <>
Soumis le : lundi 4 décembre 2017 - 11:27:39
Dernière modification le : mercredi 21 mars 2018 - 18:57:36

Fichier

6818970.pdf
Publication financée par une institution

Licence


Distributed under a Creative Commons Paternité 4.0 International License

Identifiants

Collections

Citation

Sandrine Joly, Deniz Dalkara, Vincent Pernet. Sphingosine 1-Phosphate Receptor 1 Modulates CNTF-Induced Axonal Growth and Neuroprotection in the Mouse Visual System. Neural plasticity, Hymie Anisman, 2017, pp.6818970. 〈10.1155/2017/6818970〉. 〈hal-01654649〉

Partager

Métriques

Consultations de la notice

18

Téléchargements de fichiers

12