Benchmarking the proteomic profile of animal models of mesial temporal epilepsy.

Autor: Canto AM; Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil., Godoi AB; Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil., Matos AHB; Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil., Geraldis JC; Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil., Rogerio F; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil.; Department of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil., Alvim MKM; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil.; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil., Yasuda CL; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil.; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil., Ghizoni E; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil.; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil., Tedeschi H; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil.; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil., Veiga DFT; Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil., Henning B; Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil., Souza W; Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil., Rocha CS; Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil., Vieira AS; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil.; Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil., Dias EV; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil.; Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil., Carvalho BS; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil.; Department of Statistics, Institute of Mathematics, Statistics and Scientific Computing, University of Campinas (UNICAMP), Campinas, SP, Brazil., Gilioli R; Laboratory of Animal Quality Control, University of Campinas (UNICAMP), Campinas, SP, Brazil., Arul AB; Department of Chemistry, Vanderbilt University, Nashville, Tennessee, 37235, USA., Robinson RAS; Department of Chemistry, Vanderbilt University, Nashville, Tennessee, 37235, USA., Cendes F; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil.; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil., Lopes-Cendes I; Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil.
Jazyk: angličtina
Zdroj: Annals of clinical and translational neurology [Ann Clin Transl Neurol] 2022 Apr; Vol. 9 (4), pp. 454-467. Date of Electronic Publication: 2022 Mar 03.
DOI: 10.1002/acn3.51533
Abstrakt: Objectives: We compared the proteomic signatures of the hippocampal lesion induced in three different animal models of mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS): the systemic pilocarpine model (PILO), the intracerebroventricular kainic acid model (KA), and the perforant pathway stimulation model (PPS).
Methods: We used shotgun proteomics to analyze the proteomes and find enriched biological pathways of the dorsal and ventral dentate gyrus (DG) isolated from the hippocampi of the three animal models. We also compared the proteomes obtained in the animal models to that from the DG of patients with pharmacoresistant MTLE+HS.
Results: We found that each animal model presents specific profiles of proteomic changes. The PILO model showed responses predominantly related to neuronal excitatory imbalance. The KA model revealed alterations mainly in synaptic activity. The PPS model displayed abnormalities in metabolism and oxidative stress. We also identified common biological pathways enriched in all three models, such as inflammation and immune response, which were also observed in tissue from patients. However, none of the models could recapitulate the profile of molecular changes observed in tissue from patients.
Significance: Our results indicate that each model has its own set of biological responses leading to epilepsy. Thus, it seems that only using a combination of the three models may one replicate more closely the mechanisms underlying MTLE+HS as seen in patients.
(© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Databáze: MEDLINE
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