Benchmarking the proteomic profile of animal models of mesial temporal epilepsy

Ann Clin Transl Neurol. 2022 Apr;9(4):454-467. doi: 10.1002/acn3.51533. Epub 2022 Mar 3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benchmarking
  • Disease Models, Animal
  • Epilepsy* / pathology
  • Epilepsy, Temporal Lobe* / pathology
  • Humans
  • Proteome
  • Proteomics
  • Sclerosis

Substances

  • Proteome

Grant support

This work was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico grant 311923/2019‐4; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior grant 001; Fundação de Amparo à Pesquisa do Estado de São Paulo grants 2013/07467‐1, 2013/07559‐3, 2015/12960‐4, 2016/19484‐6, 2017/2394‐0, and 2019/00213‐0.