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

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Citações na Scopus
16
Tipo de produção
article
Data de publicação
2019
Título da Revista
ISSN da Revista
Título do Volume
Editora
WILEY
Autores
TOSCANO, Eliana C. de Brito
VIEIRA, Erica L. M.
PORTELA, Ana C. D. C.
REIS, Joice L. J.
V, Marcelo Caliari
V, Alexandre Giannetti
GONCALVES, Ana P.
SIQUEIRA, Jose M.
Citação
NEUROPATHOLOGY, v.39, n.5, p.348-357, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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.
Palavras-chave
gliosis, hippocampal sclerosis, intrinsic apoptosis, temporal lobe epilepsy
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