Cell type-specific Nogo-A gene ablation promotes axonal regeneration in the injured adult optic nerve

• Verfasst von: Vajda, Flóra [VerfasserIn]
• Verfasst von: Jordi, N. [VerfasserIn]
• Verfasst von: Dalkara, D. [VerfasserIn]
• Verfasst von: Joly, S. [VerfasserIn]
• Verfasst von: Christ, F. [VerfasserIn]
• Verfasst von: Tews, Björn [VerfasserIn]
• Verfasst von: Schwab, M. E. [VerfasserIn]
• Verfasst von: Pernet, V. [VerfasserIn]
• Titel: Cell type-specific Nogo-A gene ablation promotes axonal regeneration in the injured adult optic nerve
• Verf.angabe: F. Vajda, N. Jordi, D. Dalkara, S. Joly, F. Christ, B. Tews, M.E. Schwab and V. Pernet
• Jahr: 2015
• Jahr des Originals: 2014
• Umfang: 13 S.
• Fussnoten: published online 26 September 2014 ; Gesehen am 12.02.2021
• Titel Quelle: Enthalten in: Cell death and differentiation
• Ort Quelle: Houndmills, Basingstoke : Nature Publishing Group, 1997
• Jahr Quelle: 2015
• Band/Heft Quelle: 22(2015), 2, Seite 323-335
• ISSN Quelle: 1476-5403
• DOI: doi:10.1038/cdd.2014.147
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1748199080

Abstract

Nogo-A is a well-known myelin-enriched inhibitory protein for axonal growth and regeneration in the central nervous system (CNS). Besides oligodendrocytes, our previous data revealed that Nogo-A is also expressed in subpopulations of neurons including retinal ganglion cells, in which it can have a positive role in the neuronal growth response after injury, through an unclear mechanism. In the present study, we analyzed the opposite roles of glial versus neuronal Nogo-A in the injured visual system. To this aim, we created oligodendrocyte (Cnp-Cre+/−xRtn4/Nogo-Aflox/flox) and neuron-specific (Thy1-Cretg+xRtn4flox/flox) conditional Nogo-A knock-out (KO) mouse lines. Following complete intraorbital optic nerve crush, both spontaneous and inflammation-mediated axonal outgrowth was increased in the optic nerves of the glia-specific Nogo-A KO mice. In contrast, neuron-specific deletion of Nogo-A in a KO mouse line or after acute gene recombination in retinal ganglion cells mediated by adeno-associated virus serotype 2.Cre virus injection in Rtn4flox/flox animals decreased axon sprouting in the injured optic nerve. These results therefore show that selective ablation of Nogo-A in oligodendrocytes and myelin in the optic nerve is more effective at enhancing regrowth of injured axons than what has previously been observed in conventional, complete Nogo-A KO mice. Our data also suggest that neuronal Nogo-A in retinal ganglion cells could participate in enhancing axonal sprouting, possibly by cis-interaction with Nogo receptors at the cell membrane that may counteract trans-Nogo-A signaling. We propose that inactivating Nogo-A in glia while preserving neuronal Nogo-A expression may be a successful strategy to promote axonal regeneration in the CNS.