Multi-omics analysis suggests enhanced epileptogenesis in the Cornu Ammonis 3 of the pilocarpine model of mesial temporal lobe epilepsy.
Autor: | Canto AM; Department of Medical Genetics and Genomic Medicine, School of Medical Sciences. University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil., Matos AHB; Department of Medical Genetics and Genomic Medicine, School of Medical Sciences. University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil., Godoi AB; Department of Medical Genetics and Genomic Medicine, School of Medical Sciences. University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil., Vieira AS; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil.; Department of Structural and Functional Biology, Institute of Biology. University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Aoyama BB; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil.; Department of Structural and Functional Biology, Institute of Biology. University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Rocha CS; Department of Medical Genetics and Genomic Medicine, School of Medical Sciences. University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil., Henning B; Department of Medical Genetics and Genomic Medicine, School of Medical Sciences. University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil., Carvalho BS; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil.; Department of Statistics, Institute of Mathematics, Statistics and Scientific Computing. University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Pascoal VDB; Department of Basic Sciences, Fluminense Federal University (UFF), Nova Friburgo, Rio de Janeiroz, Brazil., Veiga DFT; The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA., Gilioli R; Laboratory of Animal Quality Control, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Cendes F; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil.; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil., Lopes-Cendes I; Department of Medical Genetics and Genomic Medicine, School of Medical Sciences. University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.; Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil. |
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Jazyk: | angličtina |
Zdroj: | Hippocampus [Hippocampus] 2021 Feb; Vol. 31 (2), pp. 122-139. Date of Electronic Publication: 2020 Oct 10. |
DOI: | 10.1002/hipo.23268 |
Abstrakt: | Mesial temporal lobe epilepsy (MTLE) is a chronic neurological disorder characterized by the occurrence of seizures, and histopathological abnormalities in the mesial temporal lobe structures, mainly hippocampal sclerosis (HS). We used a multi-omics approach to determine the profile of transcript and protein expression in the dorsal and ventral hippocampal dentate gyrus (DG) and Cornu Ammonis 3 (CA3) in an animal model of MTLE induced by pilocarpine. We performed label-free proteomics and RNAseq from laser-microdissected tissue isolated from pilocarpine-induced Wistar rats. We divided the DG and CA3 into dorsal and ventral areas and analyzed them separately. We performed a data integration analysis and evaluated enriched signaling pathways, as well as the integrated networks generated based on the gene ontology processes. Our results indicate differences in the transcriptomic and proteomic profiles among the DG and the CA3 subfields of the hippocampus. Moreover, our data suggest that epileptogenesis is enhanced in the CA3 region when compared to the DG, with most abnormalities in transcript and protein levels occurring in the CA3. Furthermore, our results show that the epileptogenesis in the pilocarpine model involves predominantly abnormal regulation of excitatory neuronal mechanisms mediated by N-methyl D-aspartate (NMDA) receptors, changes in the serotonin signaling, and neuronal activity controlled by calcium/calmodulin-dependent protein kinase (CaMK) regulation and leucine-rich repeat kinase 2 (LRRK2)/WNT signaling pathways. (© 2020 Wiley Periodicals LLC.) |
Databáze: | MEDLINE |
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