NLRP3 and NLRP1 inflammasomes are up-regulated in patients with mesial temporal lobe epilepsy and may contribute to overexpression of caspase-1 and IL-β in sclerotic hippocampi.

Autor: Cristina de Brito Toscano E; Departamento de Patologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Laboratório Interdisciplinar de Investigação Médica, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: elianacbtoscano@gmail.com., Leandro Marciano Vieira É; Laboratório Interdisciplinar de Investigação Médica, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Boni Rocha Dias B; Departamento de Patologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Vidigal Caliari M; Departamento de Patologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Paula Gonçalves A; Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Núcleo Avançado de Tratamento das Epilepsias - Hospital Felício Rocho, Belo Horizonte, MG, Brazil., Varela Giannetti A; Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Maurício Siqueira J; Núcleo Avançado de Tratamento das Epilepsias - Hospital Felício Rocho, Belo Horizonte, MG, Brazil., Kimie Suemoto C; Biobank for Aging Studies, Universidade de São Paulo, São Paulo, Brazil., Elaine Paraizo Leite R; Biobank for Aging Studies, Universidade de São Paulo, São Paulo, Brazil., Nitrini R; Biobank for Aging Studies, Universidade de São Paulo, São Paulo, Brazil., Alvarenga Rachid M; Departamento de Patologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: milenerachid@gmail.com., Lúcio Teixeira A; Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, TX, United States.
Jazyk: angličtina
Zdroj: Brain research [Brain Res] 2021 Feb 01; Vol. 1752, pp. 147230. Date of Electronic Publication: 2020 Dec 29.
DOI: 10.1016/j.brainres.2020.147230
Abstrakt: Inflammation plays a role in the pathophysiology of mesial temporal lobe epilepsy (MTLE). Inflammasome pathways, including the NLRP1 and NLRP3-induced ones, promote neuroinflammation and pyroptosis through interleukin (IL)-1β and caspase-1 action. Evaluation of NLRP1 in sclerotic hippocampi is scarce and there are no data on NLRP3 in human TLE. The aim of this study was to evaluate the expression of these proteins alongside caspase-1 and IL-1β in the hippocampi of patients with TLE compared to control samples. We also sought to investigate peripheral levels of caspase-1 and IL-1β in an independent cohort. Sclerotic and control hippocampi were collected for both histological and immunohistochemical analyses of NLRP1, NLRP3, caspase-1 and IL-1β; plasma was sampled for the measurement of caspase-1 and IL-1β levels through enzyme-linked immunoassay (ELISA) and cytometric bead array (CBA). Sclerotic hippocampi displayed higher expression of the measured proteins than control. Both glia and neurons showed activation of these pathways. Additionally, increased expression of NLRP1 and NLRP3 was associated with elevated plasma levels of IL-1β and in TLE, and increased levels of peripheral caspase-1 were associated with bilateral hippocampal sclerosis (HS). In conclusion, NLRP1 and NLRP3 are up-regulated in sclerotic hippocampi, what may be responsible, at least in part, for the increased hippocampal expression of caspase-1 and IL-1β. Our data suggest a role for inflammasome activation in central and peripheral inflammation in TLE.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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