Vitamin B12 is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation

Detalhes bibliográficos
Autor(a) principal: Queiroz, Karina Barbosa de
Data de Publicação: 2020
Outros Autores: Cavalcante-Silva, Vanessa, Lopes, Flávia Lombardi, Rocha, Gifone Aguiar, D’Almeida, Vânia, Coimbra, Roney Santos
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/40627
Resumo: Fundação Oswaldo Cruz. Instituto René Rachou . Neurogenômica/Imunopatologia. Belo Horizonte, MG, Brazil.
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spelling Queiroz, Karina Barbosa deCavalcante-Silva, VanessaLopes, Flávia LombardiRocha, Gifone AguiarD’Almeida, VâniaCoimbra, Roney Santos2020-04-03T17:28:07Z2020-04-03T17:28:07Z2020QUEIROZ, Karina Barbosa de et al. Vitamin B12 is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation Journal of Neuroinflammation, v. 2020, p. 1-12, 2020.1742-2094https://www.arca.fiocruz.br/handle/icict/4062710.1186/s12974-020-01763-yengBMCVitamin B12 is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto René Rachou . Neurogenômica/Imunopatologia. Belo Horizonte, MG, Brazil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Psicobiologia. São Paulo, SP, Brazil.Faculdade de Medicina Veterinária de Araçatuba. Universidade Estadual Paulista. SP, Brazil.Universidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Propedêutica Complementar. Laboratório de Pesquisa em Bacteriologia. Belo Horizonte, MG , Brazil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Psicobiologia. São Paulo, SP, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou . Neurogenômica/Imunopatologia. Belo Horizonte, MG, Brazil.Background: Bacterial meningitis (BM) causes apoptotic damage to the hippocampus and homocysteine (Hcy) accumulation to neurotoxic levels in the cerebrospinal fluid of children. The Hcy pathway controls bioavailability of methyl, and its homeostasis can be modulated by vitamin B12, a cofactor of the methionine synthase enzyme. Herein, the neuroprotective potential and the underlying mode of action of vitamin B12 adjuvant therapy were assessed in an infant rat model of BM. Methods: Eleven-day old rats were intracysternally infected with Streptococcus pneumoniae serotype 3, or saline, treated with B12 or placebo, and, 24 h after infection, their hippocampi were analyzed for apoptosis in the dentate gyrus, sulfur amino acids content, global DNA methylation, transcription, and proximal promoter methylation of candidate genes. Differences between groups were compared using 2-way ANOVA followed by Bonferroni post hoc test. Correlations were tested with Spearman’s test. Results: B12 attenuated BM-induced hippocampal apoptosis in a Hcy-dependent manner (r = 0.80, P < 0.05). BM caused global DNA hypomethylation; however, B12 restored this parameter. Accordingly, B12 increased the methylation capacity of hippocampal cells from infected animals, as inferred from the ratio S-adenosylmethionine (SAM):S-adenosylhomocysteine (SAH) in infected animals. BM upregulated selected pro-inflammatory genes, and this effect was counteracted by B12, which also increased methylation of CpGs at the promoter of Ccl3 of infected animals. Conclusion: Hcy is likely to play a central role in hippocampal damage in the infant rat model of BM, and B12 shows an anti-inflammatory and neuroprotective action through methyl-dependent epigenetic mechanisms.MeningitisNeuroprotectionVitamin B12EpigeneticsHomocysteineDNA methylationinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83082https://www.arca.fiocruz.br/bitstream/icict/40627/1/license.txt9193a7c197bc67acd023525e72a03240MD51ORIGINALVitamin B12 is neuroprotective.pdfVitamin B12 is neuroprotective.pdfapplication/pdf1757374https://www.arca.fiocruz.br/bitstream/icict/40627/2/Vitamin%20B12%20is%20neuroprotective.pdf82e0eaecb5a07a17271192ea38b06f75MD52TEXTVitamin B12 is neuroprotective.pdf.txtVitamin B12 is neuroprotective.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Vitamin B12 is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation
title Vitamin B12 is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation
spellingShingle Vitamin B12 is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation
Queiroz, Karina Barbosa de
Meningitis
Neuroprotection
Vitamin B12
Epigenetics
Homocysteine
DNA methylation
title_short Vitamin B12 is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation
title_full Vitamin B12 is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation
title_fullStr Vitamin B12 is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation
title_full_unstemmed Vitamin B12 is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation
title_sort Vitamin B12 is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation
author Queiroz, Karina Barbosa de
author_facet Queiroz, Karina Barbosa de
Cavalcante-Silva, Vanessa
Lopes, Flávia Lombardi
Rocha, Gifone Aguiar
D’Almeida, Vânia
Coimbra, Roney Santos
author_role author
author2 Cavalcante-Silva, Vanessa
Lopes, Flávia Lombardi
Rocha, Gifone Aguiar
D’Almeida, Vânia
Coimbra, Roney Santos
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Queiroz, Karina Barbosa de
Cavalcante-Silva, Vanessa
Lopes, Flávia Lombardi
Rocha, Gifone Aguiar
D’Almeida, Vânia
Coimbra, Roney Santos
dc.subject.en.pt_BR.fl_str_mv Meningitis
Neuroprotection
Vitamin B12
Epigenetics
Homocysteine
DNA methylation
topic Meningitis
Neuroprotection
Vitamin B12
Epigenetics
Homocysteine
DNA methylation
description Fundação Oswaldo Cruz. Instituto René Rachou . Neurogenômica/Imunopatologia. Belo Horizonte, MG, Brazil.
publishDate 2020
dc.date.accessioned.fl_str_mv 2020-04-03T17:28:07Z
dc.date.available.fl_str_mv 2020-04-03T17:28:07Z
dc.date.issued.fl_str_mv 2020
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv QUEIROZ, Karina Barbosa de et al. Vitamin B12 is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation Journal of Neuroinflammation, v. 2020, p. 1-12, 2020.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/40627
dc.identifier.issn.pt_BR.fl_str_mv 1742-2094
dc.identifier.doi.none.fl_str_mv 10.1186/s12974-020-01763-y
identifier_str_mv QUEIROZ, Karina Barbosa de et al. Vitamin B12 is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation Journal of Neuroinflammation, v. 2020, p. 1-12, 2020.
1742-2094
10.1186/s12974-020-01763-y
url https://www.arca.fiocruz.br/handle/icict/40627
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BMC
publisher.none.fl_str_mv BMC
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/40627/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/40627/2/Vitamin%20B12%20is%20neuroprotective.pdf
https://www.arca.fiocruz.br/bitstream/icict/40627/3/Vitamin%20B12%20is%20neuroprotective.pdf.txt
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