Charcot-Marie-Tooth-1A and sciatic nerve crush rat models:insights from proteomics  

作　　者：Zeina Msheik Stephanie Durand Emilie Pinault Martial Caillaud Laetitia Vignaud Fabrice Billet Mohamed El Massry Alexis Desmoulière 

机构地区：[1]UR20218 NeurIT(NEURopathies périphériques et Innovation Thérapeutique),University of Limoges,Limoges,France [2]BISCEm(Biologie Intégrative SantéChimie Environnement)Platform,US 42 Inserm/UAR 2015 CNRS,University of Limoges,Limoges,France [3]UMR 1308 Inserm/CHU–CAPTuR(Contrôle de l’Activation cellulaire,Progression Tumorale et Résistance thérapeutique),University of Limoges,Limoges,France [4]Inserm UMR1235–TENS(The Enteric Nervous System in Gut and Brain Diseases),University of Nantes,Nantes,France

出　　处：《Neural Regeneration Research》2023年第6期1354-1363,共10页中国神经再生研究（英文版）

基　　金：supported by a doctoral fellowship from the European Union(European Regional Development Fund).

摘　　要：The sensorimotor and histological aspects of peripheral neuropathies were already studied by our team in two rat models:the sciatic nerve crush and the Charcot-Marie-Tooth-1A disease.In this study,we sought to highlight and compare the protein signature of these two pathological situations.Indeed,the identification of protein profiles in diseases can play an important role in the development of pharmacological targets.In fact,Charcot-Marie-Tooth-1A rats develop motor impairments that are more severe in the hind limbs.Therefore,for the first time,protein expression in sciatic nerve of Charcot-Marie-Tooth-1A rats was examined.First,distal sciatic nerves were collected from Charcot-Marie-Tooth-1A and uninjured wild-type rats aged 3 months.After protein extraction,sequential window acquisition of all theoretical fragment ion spectra liquid chromatography and mass spectrometry was employed.445 proteins mapped to Swiss-Prot or trEMBL Uniprot databases were identified and quantified.Of these,153 proteins showed statistically significant differences between Charcot-Marie-Tooth-1A and wild-type groups.The majority of these proteins were overexpressed in Charcot-Marie-Tooth-1A.Hierarchical clustering and functional enrichment using Gene Ontology were used to group these proteins based on their biological effects concerning Charcot-Marie-Tooth-1A pathophysiology.Second,proteomic characterization of wild-type rats subjected to sciatic nerve crush was performed sequential window acquisition of all theoretical fragment ion spectra liquid chromatography and mass spectrometry.One month after injury,distal sciatic nerves were collected and analyzed as described above.Out of 459 identified proteins,92 showed significant differences between sciatic nerve crush and the uninjured wild-type rats used in the first study.The results suggest that young adult Charcot-Marie-Tooth-1A rats(3 months old)develop compensatory mechanisms at the level of redox balance,protein folding,myelination,and axonogenesis.These mechanisms seem insufficient

关 键 词：Charcot-Marie-Tooth-1A endoplasmic reticulum Gene Ontology NEUROGENESIS oxidative stress PROTEOMICS rat repair sciatic nerve crush SWATH-MS 

分 类 号：R741[医药卫生—神经病学与精神病学]