Multi-omics analysis suggests enhanced epileptogenesis in theCornu Ammonis3 of the pilocarpine model of mesial temporal lobe epilepsy

Author(s):Show less -

Canto, Amanda M. ^{[1, 2]} ; Matos, Alexandre H. B. ^{[1, 2]} ; Godoi, Alexandre B. ^{[1, 2]} ; Vieira, Andre S. ^{[3, 1]} ; Aoyama, Beatriz B. ^{[3, 1]} ; Rocha, Cristiane S. ^{[1, 2]} ; Henning, Barbara ^{[1, 2]} ; Carvalho, Benilton S. ^{[1, 4]} ; Pascoal, Vinicius D. B. ^[5] ; Veiga, Diogo F. T. ^[6] ; Gilioli, Rovilson ^[7] ; Cendes, Fernando ^{[8, 1]} ; Lopes-Cendes, Iscia ^{[1, 2]}

Affiliation

^[1] Brazilian Inst Neurosci & Neurotechnol BRAINN, Campinas, SP - Brazil

^[2] Univ Campinas UNICAMP, Dept Med Genet & Genom Med, Sch Med Sci, 126 Cidade Univ Zeferino Vaz, Campinas, SP - Brazil

^[3] Univ Campinas UNICAMP, Dept Struct & Funct Biol, Inst Biol, Campinas, SP - Brazil

^[4] Univ Campinas UNICAMP, Dept Stat, Inst Math Stat & Sci Comp, Campinas, SP - Brazil

^[5] Fluminense Fed Univ UFF, Dept Basic Sci, Nova Friburgo, RJ - Brazil

^[6] Jackson Lab Genom Med, Farmington, CT - USA

^[7] Univ Campinas UNICAMP, Lab Anim Qual Control, Campinas, SP - Brazil

^[8] Univ Campinas UNICAMP, Sch Med Sci, Dept Neurol, Campinas, SP - Brazil

• Document type: Journal article
• Source: HIPPOCAMPUS; v. 31, n. 2, p. 122-139, FEB 2021.
• Web of Science Citations: 1

Abstract

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) andCornu Ammonis3 (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. (AU)

• FAPESP's process: 16/19484-6 - Quantitative proteomic analysis of neuronal tissue obtained from patients and animal models of epilepsy
• Grantee: Barbara Henning Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/12333-0 - A statistical method for detection of copy number variation using next-generation sequencing data
• Grantee: Barbara Henning Silva
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 19/04335-3 - Identification of differentially phosphorylated proteins in the brain tissue resected from patients with mesial temporal lobe epilepsy with hippocampal sclerosis
• Grantee: Amanda Morato Do Canto
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 13/08635-5 - TRANSCRIPTOME ANALYSIS IN ANIMAL MODELS OF MESIAL TEMPORAL LOBE EPILEPSY
• Grantee: Alexandre Hilário Berenguer de Matos
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/07559-3 - BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology
• Grantee: Fernando Cendes
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 19/00213-0 - Metabolomic analysis from plasma of patients with mesial temporal lobe epilepsy: searching for drug resistant biomarkers
• Grantee: Alexandre Barcia de Godoi
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 15/12960-4 - Proteomic analysis of hippocampal tissues obtained from patients and animal model of Mesial Temporal Lobe Epilepsy: a comparative study
• Grantee: Amanda Morato Do Canto
• Support Opportunities: Scholarships in Brazil - Doctorate