title: Lentivirus-mediated PGC-1α overexpression protects against traumatic spinal cord injury in rats.
abstract: Peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1α) is a crucial neuronal regulator in the brain. However, its role in the spinal cord and the underlying regulating mechanisms remain poorly understood. Our previous study demonstrated that PGC-1α is significantly down-regulated following acute spinal cord injury (SCI) in rats. The current study aimed to explore the effects of PGC-1α overexpression on the injured spinal cord by establishing a contusive SCI model in adult Sprague-Dawley rats, followed by immediate intraspinal injection of lentiviral vectors at rostral and caudal sites 3mm from the lesion epicenter. Hindlimb motor function was monitored using the Basso-Beattie-Bresnahan Locomotor Rating Scale (BBB scores), and cords were collected. Transfection efficiency analysis showed that lentivirus successfully induced enhanced PGC-1α expression. This resulted in attenuated apoptotic changes and a greater number of surviving spinal neurons, as determined by transmission electron microscopy and Nissl staining, respectively. Western blot and immunofluorescence analyses revealed increased growth-associated protein 43 and 5-hydroxytryptamine expression, two key markers of axonal regeneration. Importantly, BBB scores showed improved hindlimb motor functional recovery. Moreover, quantitative real-time polymerase chain reaction analysis demonstrated significantly inhibited RhoA, ROCK1, and ROCK2 mRNA expression, revealing a potential mechanism of PGC-1α overexpression following traumatic SCI. Altogether, these results suggest that gene delivery of PGC-1α exerts a significant neuroprotective effect following traumatic SCI, which could serve as a promising treatment for repair of the injured cord, and RhoA-ROCK pathway inhibition may partially underlie this neuroprotection.
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Lang
authors.affiliation: Department of Sports Medicine, Research Center of Sports Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Shuangfei
authors.initials: S
authors.lastname: Ni
authors.affiliation: Department of Sports Medicine, Research Center of Sports Medicine, Xiangya Hospital, Central South University, Changsha 410008, China. Electronic address: hongbinlu@hotmail.com.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Lu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004195:Disease Models, Animal; D019922:GAP-43 Protein / Q000378:metabolism; D015316:Genetic Therapy; D005822:Genetic Vectors; D006614:Hindlimb / Q000503:physiopathology; D016086:Lentivirus / Q000235:genetics; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D000066829:Neuroprotection / Q000502:physiology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics* / Q000378:metabolism*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D058630:Spinal Cord Regeneration / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D019922:GAP-43 Protein; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012701:Serotonin; C578418:ROCK1 protein, rat; C580818:ROCK2 protein, rat; D054460:rho-Associated Kinases; C000621224:RhoA protein, rat; D020741:rho GTP-Binding Proteins
keywords: PGC-1α; RhoA–ROCK pathway; axonal regeneration; lentivirus; neuronal apoptosis; spinal cord injury