MicroRNA-7 promotes motor function recovery following spinal cord injury in mice

Abstract

Spinal cord injury (SCI) is a devastating neurological condition for which there are no effective therapies. Following an initial injury, there is a cascade of multiple downstream events termed secondary injury. Thus, therapeutic approaches targeting a single pathway may not offer the best solution for treating SCI. One of the most attractive properties of microRNAs (miR) as potential therapeutics is that they are highly effective in regulating complex biological pathways by targeting multiple genes and pathways. The current study investigated the role of miR-7-5p (miR-7), which was previously shown to have neuroprotective functions, in promoting motor function recovery following SCI. We used an adeno-associated virus 1 (AAV1) vector to deliver the gene encoding miR-7 to the spinal cord of adult mice and found that this virus was mainly transduced into the neurons of the spinal cord. Transduction of AAV1-miR-7 improved hindlimb locomotor function following SCI over an 8-week observation period. This improvement was accompanied by reduced neuronal loss in the lesion. In addition, the beneficial effect of miR-7 was associated with enhanced levels of TH-positive axons in the lesion. Taken together, we suggest that miR-7 improves motor function recovery after SCI by protecting neuronal death and increasing axon levels. These findings suggest that miR-7 could be developed as a potential treatment for SCI in human.