C. JUZWIK, B. MORQUETTE, Y. ZHANG, E. GOWING, C. BOUDREAU-PINSONNEAULT, V. VANGOOR, R. PASTERKAMP, C. MOORE, A. BAR-OR, A. E. FOURNIER
Neuroinflammation can positively influence axon regeneration following injury in the central nervous system (CNS) but the molecular mechanisms underlying this effect are not fully understood. We have evaluated how microRNAs may be regulated in the context of inflammation because they target multiple mRNAs simultaneously and may help to identify signalling hubs that can be targeted to promote regeneration. We identified miR-383 as a miRNA that is down regulated in neurons in response to neurite outgrowth-promoting astrocyte conditioned media (ACM). We also found that miR-383 was down regulated in Retinal Ganglion Cells (RGCs) exposed to zymosan, a yeast cell wall protein that stimulates inflammation in the eye and promotes axon regeneration following optic nerve crush. miR383 down regulation promotes axon growth in vitro and injection of a miR-383 inhibitor into the eye promotes axon regeneration following optic nerve crush. Previous studies have demonstrated that astrocyte-derived CNTF, signals to injured RGCs and promotes their regeneration in response to zymosan injection. We found that neurons treated with CNTF down regulated the expression of miR-383. Further, we have acquired evidence that inhibiting miR-383 de-represses the expression of mitochondrial antioxidant genes and microtubule-associated proteins that are important for the pro-regenerative effects of the miR383 inhibitor. Together, we have implicated miR-383 as a molecule that suppresses axon regeneration and that can be further explored to identify novel signalling hubs that may be targeted to promote repair.
*C. JUZWIK1, B. MORQUETTE1, Y. ZHANG1, E. GOWING2, C. BOUDREAU-PINSONNEAULT3, V. VANGOOR4, R. PASTERKAMP4, C. MOORE5, A. BAR-OR6, A. E. FOURNIER1;
1Dept Neurol & Neurosur, McGill Univ., Montreal, QC, Canada; 2CRCHUM, Montreal, QC, Canada; 3Inst. De Recherche Clinique De Montréal, Montreal, QC, Canada; 4UMC Utrecht, Utrecht, Netherlands; 5Mem. Univ., St John’s, NL, Canada; 6Perelman Sch. of Med., Philadelphia, PA. Inhibition of miR-383 promotes axon regeneration following injury. Program No. 115.11. 2018 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2018. Online.
Grant Support: MSSOC Grant