Vitamin B-12 is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation

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Autor(es): dc.contributorFundacao Oswaldo Cruz-
Autor(es): dc.contributorUniversidade Federal de São Paulo (UNIFESP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorUniversidade Federal de Minas Gerais (UFMG)-
Autor(es): dc.creatorQueiroz, Karina Barbosa de-
Autor(es): dc.creatorCavalcante-Silva, Vanessa-
Autor(es): dc.creatorLopes, Flavia Lombardi [UNESP]-
Autor(es): dc.creatorRocha, Gifone Aguiar-
Autor(es): dc.creatorD'Almeida, Vania-
Autor(es): dc.creatorCoimbra, Roney Santos-
Data de aceite: dc.date.accessioned2022-02-22T00:11:56Z-
Data de disponibilização: dc.date.available2022-02-22T00:11:56Z-
Data de envio: dc.date.issued2020-12-09-
Data de envio: dc.date.issued2020-12-09-
Data de envio: dc.date.issued2020-04-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1186/s12974-020-01763-y-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/197334-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/197334-
Descrição: dc.descriptionBackground 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 B-12, a cofactor of the methionine synthase enzyme. Herein, the neuroprotective potential and the underlying mode of action of vitamin B-12 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 B-12 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 B-12 attenuated BM-induced hippocampal apoptosis in a Hcy-dependent manner (r = 0.80, P < 0.05). BM caused global DNA hypomethylation; however, B-12 restored this parameter. Accordingly, B-12 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 B-12, 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 B-12 shows an anti-inflammatory and neuroprotective action through methyl-dependent epigenetic mechanisms.-
Descrição: dc.descriptionInova Fundacao Oswaldo Cruz (FIOCRUZ)-
Descrição: dc.descriptionFundacao Oswaldo Cruz, FIOCRUZ, IRR, Neurogen Imunopatol, Av Augusto de Lima 1715, BR-30190002 Belo Horizonte, MG, Brazil-
Descrição: dc.descriptionUniv Fed Sao Paulo, Dept Psicobiol, EPM, UNIFESP, Rua Botucatu 740, BR-04023062 Sao Paulo, SP, Brazil-
Descrição: dc.descriptionUniv Estadual Paulista, Fac Med Vet Aracatuba, UNESP, R Clovis Pestana 793, BR-16050680 Aracatuba, SP, Brazil-
Descrição: dc.descriptionUniv Fed Minas Gerais, Fac Med, Dept Propedeut Complementar, Lab Pesquisa Bacteriol, Av Prof Alfredo Balena 190, BR-30130100 Belo Horizonte, MG, Brazil-
Descrição: dc.descriptionUniv Estadual Paulista, Fac Med Vet Aracatuba, UNESP, R Clovis Pestana 793, BR-16050680 Aracatuba, SP, Brazil-
Formato: dc.format12-
Idioma: dc.languageen-
Publicador: dc.publisherBmc-
Relação: dc.relationJournal Of Neuroinflammation-
???dc.source???: dc.sourceWeb of Science-
Palavras-chave: dc.subjectMeningitis-
Palavras-chave: dc.subjectNeuroprotection-
Palavras-chave: dc.subjectVitamin B-12-
Palavras-chave: dc.subjectEpigenetics-
Palavras-chave: dc.subjectHomocysteine-
Palavras-chave: dc.subjectDNA methylation-
Título: dc.titleVitamin B-12 is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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