title: Exendin-4 Enhances Motor Function Recovery via Promotion of Autophagy and Inhibition of Neuronal Apoptosis After Spinal Cord Injury in Rats.
abstract: Autophagy occurs prior to apoptosis and plays an important role in cell death regulation during spinal cord injury (SCI). This study aimed to determine the effects and potential mechanism of the glucagon-like peptide-1 (GLP-1) agonist extendin-4 (Ex-4) in SCI. Seventy-two male Sprague Dawley rats were randomly assigned to sham, SCI, 2.5 μg Ex-4, and 10 μg Ex-4 groups. To induce SCI, a 10-g iron rod was dropped from a 20-mm height to the spinal cord surface. Ex-4 was administered via intraperitoneal injection immediately after surgery. Motor function evaluation with the Basso Beattie Bresnahan (BBB) locomotor rating scale indicated significantly increased scores (p < 0.01) in the Ex-4-treated groups, especially 10 μg, which demonstrated the neuroprotective effect of Ex-4 after SCI. The light chain 3-II (LC3-II) and Beclin 1 protein expression determined via western blot and the number of autophagy-positive neurons via immunofluorescence double labeling were increased by Ex-4, which supports promotion of autophagy (p < 0.01). The caspase-3 protein level and neuronal apoptosis via transferase UTP nick end labeling (TUNEL)/NeuN/DAPI double labeling were significantly reduced in the Ex-4-treated groups, which indicates anti-apoptotic effects (p < 0.01). Finally, histological assessment via Nissl staining demonstrated the Ex-4 groups exhibited a significantly greater number of surviving neurons and less cavity (p < 0.01). To our knowledge, this is the first study to indicate that Ex-4 significantly enhances motor function in rats after SCI, and these effects are associated with the promotion of autophagy and inhibition of apoptosis.
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University, Jinzhou, 121000, China.
authors.forename: Hao-Tian
authors.initials: HT
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University, Jinzhou, 121000, China.
authors.forename: Xing-Zhang
authors.initials: XZ
authors.lastname: Zhao
authors.affiliation: Postgraduate Training Base of General Hospital of Armed Police Forces, Liaoning Medical University, Beijing, 100039, China.
authors.forename: Xin-Ran
authors.initials: XR
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University, Jinzhou, 121000, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University, Jinzhou, 121000, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Jia
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University, Jinzhou, 121000, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University, Jinzhou, 121000, China.
authors.forename: Ji-Quan
authors.initials: JQ
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University, Jinzhou, 121000, China. flanzz2014@163.com.
authors.forename: Zhong-Kai
authors.initials: ZK
authors.lastname: Fan
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Liaoning Medical University, Jinzhou, 121000, China. ganglv2014@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Lv
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1 / Q000378:metabolism; D001522:Behavior, Animal; D053148:Caspase 3 / Q000378:metabolism; D000077270:Exenatide; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D014688:Venoms / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000071186:Beclin-1; D053148:Caspase 3; D000077270:Exenatide; D008869:Microtubule-Associated Proteins; D010455:Peptides; D014688:Venoms; C526109:Anxa3 protein, rat
keywords: Apoptosis; Autophagy; Extendin-4; Spinal cord injury