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

Eliana Cristina de Brito Toscano, Érica Leandro Marciano Vieira, Bárbara Boni Rocha Dias, Marcelo Vidigal Caliari, Ana Paula Gonçalves, Alexandre Varela Giannetti, José Maurício Siqueira, Claudia Kimie Suemoto, Renata Elaine Paraizo Leite, Ricardo Nitrini, Milene Alvarenga Rachid, Antônio Lúcio Teixeira

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60 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number147230
JournalBrain Research
Volume1752
DOIs
StatePublished - Feb 1 2021
Externally publishedYes

Keywords

  • Hippocampal sclerosis
  • Inflammasome
  • Neuroinflammation
  • Pyroptosis
  • Temporal lobe epilepsy

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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