MS275 reduces seizure-induced brain damage in developing rats by regulating p38 MAPK signaling pathways and epigenetic modification.
Brain Res
; 1745: 146932, 2020 10 15.
Article
em En
| MEDLINE
| ID: mdl-32522630
ABSTRACT
Seizure is a common acute and severe disease in infants and children. Recurrent seizures or persistent seizures may cause irreversible brain damage. Mitogen activated protein kinase (MAPK) signaling pathway is associated with an inflammatory response, however it's involvement in the pathological process of seizures is not clear. Histone deacetylase inhibitors (HDACi) have promising neuroprotective effects through epigenetic regulation. Therefore, this study aimed to investigate the mechanism of HDACi MS275 on p38 MAPK signaling pathway and p38 histone modifications in developing rats post-seizure. Intraperitoneal administration of Pentylenetetrazole (PTZ) was used to induce developing rat seizures, and MS275 (5 or 10 mg/kg) was injected intraperitoneally 2 h before PTZ injection. Hippocampal tissues were sampled at 24 h post-seizures for protein and mRNA levels of p38ãMK2ãCREB and IL-6. Neuronal apoptosis and microglia activation significantly increased after PTZ treatment. However, pretreatment with MS275 attenuated these effects as well as increased seizure latency and decreased seizure scores. Furthermore, MS275 was found to inhibit the expression of p38 by increasing histone H3 and H4 acetylation and decreasing histone H3 and H4 methylation. This study thereby demonstrates that HDACi MS275 can reduce the inflammatory response associated with seizure-induced brain injury through inhibiting the p38 MAPK signaling pathway and p38 gene expression.
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Base de dados:
MEDLINE
Assunto principal:
Convulsões
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Sistema de Sinalização das MAP Quinases
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Proteínas Quinases p38 Ativadas por Mitógeno
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Inibidores de Histona Desacetilases
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article