Inhibition by rno-circRNA-013017 of the apoptosis of motor neurons in anterior horn and descending axonal degeneration in rats after traumatic spinal cord injury

Abstract

IntroductionSpinal cord injury (SCI) often causes continuous neurological damage to clinical patients. Circular RNAs (circRNAs) are related to a lot of diseases, including SCI. We previously found five candidate circRNAs which were likely to regulate the secondary pathophysiological changes in rat model after traumatic SCI.MethodsIn this study, we first selected and overexpressed target circRNA in rats. We then explored its functional roles using various functional assays in a rat model after SCI.ResultsWe found that rno-circRNA-013017—the selected target circRNA—reduced neuron apoptosis, preserved the survival and activity of motor neurons, and regulated apoptosis-related proteins at 3 days post-SCI using western blot, immunofluorescence and polymerase chain reaction. Additionally, we found that rno-circRNA-013017 inhibited descending axonal degeneration and preserved motor neurons and descending axons at 6 weeks post-SCI using immunofluorescence, biotin dextran amine diffusion tensor imaging. Finally, the overexpression of rno-circRNA-013017 promoted the locomotor function of rats after SCI using open-field test and gait analysis.ConclusionFocusing on the functions of rno-circRNA-013017, this study provides new options for future studies exploring therapeutic targets and molecular mechanisms for SCI.

The roles of circular RNAs in nerve injury and repair

“…Moreover, rno-circRNA-013017 was significantly down-regulated in rats after injury. Overexpression of rno-circRNA-013017 was found to inhibit apoptosis of motor neurons in the spinal anterior horn 3 days after SCI, thereby contributing to motor function in rats after SCI ( Qin et al, 2022 ). Circ-Ctnnb1 exhibits high expression in both the rat model of SCI and neuronal cells challenged by hypoxia.…”

Roles of Aging, Circular RNAs, and RNA Editing in the Pathogenesis of Amyotrophic Lateral Sclerosis: Potential Biomarkers and Therapeutic Targets

“…Taken together, although changes in the expression of circRNAs have been proposed to be associated with ALS pathogenesis-related molecular change, direct evidence suggesting the role of the expression alteration of circRNAs in ALS pathogenesis remains elusive. Moreover, although rno_circ_013017 inhibits motor neuron apoptosis in rats with spinal cord injury [123], the role of circRNA in motor neuron biology in healthy elderly people or ALS patients has not been reported. Further knowledge on the etiological roles of circRNAs in motor neuron death in ALS will elucidate the interplay of several circRNAs in brain aging and neurodegeneration.…”