Study On Inhibition Of MTORC1 Signaling By N-3 Polyunsaturated Fatty Acids Promoting Locomotor Recovery After Spinal Cord Injury

BackgroundSpinal cord injury(SCI)is a common disease of the central nervous system,and presents characteristics of the high incidence,high morbidity and high cost clinically.To explore the effective treatment measures has been the hotspot and difficulty of medical research.A large number of research to try to repair SCI,the axonal regeneration and functional recovery after injury have certain to improve,but completely repair has a certain distance from damage.With the deepening of the research,found that n-3PUFAs are closely involved in the physiological activities of the nervous and immune systems,they could change the liquidity of the nerve cell membrane,thus affecting the neurotransmitter synthesis,play an important role in the occurrence and the process of repair of spinal cord injury.Through nutrient,energy growth factor and stress signaling pathway,Mammals rapamycin target protein receptor(mTOR)regulates cell metabolism,growth,proliferation,survival and autophagy;Studies have shown that inhibiting mTORCl can enhance autophagy and help repair injuries.Object To explore the effect of n-3PUFAs on locomotor recovery after SCI and the mechanism of it.Methods Sprague-Dawley rats were randomly grouped and fed diets with different contents of n-3PUFAs,a model of spinal cord contusion was created at the T10 spinal segment.The preoperative and postoperative compositions of PUFAs were analyzed by gas chromatography,motor function recovery afrer SCI was evaluate by behavior and electrophysiological detections,the tissue repair and the activities of mTORC1 and autophagy at injured spinal cord were assessed and detected through real-time reverse transcription-polymerase chain reaction,fluorescent immunohistochemical staining and western blot.In addition,in vitro experiment was established to confirm the role of PUFAs on mTORC1 and the autophagy in nerve cell.Results The n-3 PUFA level and the ratio of n-3 PUFA to n-6 PUFA in the spinal cord and serum of rats fed a high-n-3 PUFA diet were higher both before and after operation(P<0.05).Additionally,rats in the high-n-3 PUFA group showed improved motor function recovery,spinal cord repair-related protein level and autophagy ability and decreased mTORC1 activity(P<0.05).In vitro n-3PUFAs inhibited mTORCl and enhanced autophagy.Conclusion Exogenous dietary n-3 PUFAs can inhibit mTORCl signaling and enhance autophagy,promoting locomotor recovery after SCI in rats.