title: The importance of EHD1 in neurite outgrowth contributing to the functional recovery after spinal cord injury.
abstract: Traumatic spinal cord injury is one of the most common and severe problems for using NGF to promote the neurite outgrowth of survival neurons. EHD1 regulates and controls the endocytosis and transportation of neurotrophins and transmembrane cargo via recycling endosome for neurite outgrowth. TrkA is particularly considered to be a functional specific recepter in the cell membrane for NGF and is activated upon NGF binding. The transcytosis of TrkA is dependent on Rab11 recycling endosomes and is promoted by NGF signaling itself at the axon terminal. In this study, we established an acute spinal cord contusion injury model in adult rats to investigate the potential role of EHD1 during the pathological process of SCI. Western blot analysis suggested that EHD1 expression was low in the sham-operated adult rat spinal cords and was significantly up-regulated 1d after injury. Immunohistochemical staining detected the general distribution of EHD1 protein in both the gray and white matter of adult rat spinal cords. Double immunofluorescent staining indicated that EHD1 was expressed in neurons, astrocytes and microglias in the adult rat spinal cord, and obvious changes of EHD1 expression occurred in neurons during SCI pathological process. Significant up-regulation of EHD1 expression was observed in MAP2 positive neurons at 1 day after SCI, in comparison with the sham-operated control, which indicated that EHD1 might play a vital role in neurite outgrowth. Our data indicated that EHD1 could interact with TrkA, and is in the upstream of TrkA. EHD1 up-regulated the expression of TrkA in the glutamate stimulated primary neurons. Based on our experimental data, we boldly conclude that EHD1 regulates the recycling of TrkA back to cell membrane, improving the utilization efficiency of the NGF, which is vital for neurite outgrowth and functional recovery after spinal cord injury.
authors.affiliation: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, People's Republic of China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Chunshuai
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, People's Republic of China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China. Electronic address: zhimingcui@126.com.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Wensen
authors.initials: W
authors.lastname: Ding
authors.affiliation: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, People's Republic of China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Bao
authors.affiliation: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Guanhua
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000502:physiology*; D018698:Glutamic Acid / Q000494:pharmacology; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000071446:Neuronal Outgrowth / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013997:Time Factors; D014162:Transfection; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; C549917:EHD1 protein, rat; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins; D018698:Glutamic Acid; D020917:Receptor, trkA
keywords: EHD1; NGF; Neurite outgrowth; SCI; TrkA