Bcl-2/Bax ratio increase does not prevent apoptosis of glia and granular neurons in patients with temporal lobe epilepsy

Eliana C.de Brito Toscano, Érica L.M. Vieira, Ana C.D.C. Portela, Joice L.J. Reis, Marcelo V. Caliari, Alexandre V. Giannetti, Ana P. Gonçalves, José M. Siqueira, Claudia K. Suemoto, Renata E.P. Leite, Ricardo Nitrini, Antônio L. Teixeira, Milene A. Rachid

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Temporal lobe epilepsy (TLE) is usually associated with hippocampal sclerosis (HS), characterized by gliosis and neuronal loss, mainly in the cornus ammonis (CA). Regardless the type of HS, gliosis is associated with neuronal loss. Indeed, glial reactivation seems to induce both neuronal and glial apoptosis. Anti-apoptotic mechanisms are also activated in order to contain the cell death in chronic epilepsy. However, the role of the intrinsic apoptosis pathway in human TLE is unclear, mainly in relation to glial death. The purpose of this study was to evaluate the reactive gliosis areas in parallel with Bcl-2/Bax ratio and active caspase 3 immunoreactivity in hippocampi of TLE patients in comparison with control hippocampi. We also sought to investigate whether the levels of these markers were correlated with TLE clinical parameters. Paraffin-embedded sclerotic and control hippocampi were collected for immunohistochemical analyses of glial fibrillary acidic protein (GFAP), human leucocyte antigen DR (HLA-DR), neuronal nuclei protein (NeuN), Bax, Bcl-2 and active caspase 3. Sclerotic hippocampi presented higher immunoreactivity areas of GFAP and HLA-DR than controls, with similar values in HS types 1 and 2. Bcl-2 protein expression was increased in epileptic hippocampi, while Bax expression was similar to controls. Despite Bcl2/Bax ratio increase, granular neurons and glia exhibited active caspase 3 expression in TLE hippocampi, while controls did not show staining for the same marker. In conclusion, glial and neuronal death is increased in sclerotic hippocampi, independently of HS type, and co-localized with gliosis. Furthermore, Bcl-2/Bax ratio increase does not prevent expression of active caspase 3 by glia and granular neurons in TLE.

Original languageEnglish (US)
Pages (from-to)348-357
Number of pages10
JournalNeuropathology
Volume39
Issue number5
DOIs
StatePublished - Oct 1 2019
Externally publishedYes

Keywords

  • gliosis
  • hippocampal sclerosis
  • intrinsic apoptosis
  • temporal lobe epilepsy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology

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