Effects of SAHA on hippocampal TLR4/MYD88 signaling and neuronal apoptosis after seizure in developing rats
10.3969/j.issn.1000-4718.2016.07.009
- VernacularTitle:SAHA对发育期大鼠惊厥后海马TLR4／MYD88信号通路及神经元凋亡的影响
- Author:
Qingpeng HU
;
Xiangyi HUANG
- Publication Type:Journal Article
- Keywords:
Histone deacetylase inhibitor;
Vorinostat;
Seizure;
Hippocampus
- From:
Chinese Journal of Pathophysiology
2016;32(7):1208-1213
- CountryChina
- Language:Chinese
-
Abstract:
[ ABSTRACT] AIM:To investigate the effect of vorinostat ( suberoylanilide hydroxamic acid, SAHA) , a histone deacetylase inhibitor, on seizure-induced brain damage in developing rats and its mechanism.METHODS:Male Sprague-Dawley rats (n=32) were randomly divided into control group, pentylenetetrazole (PTZ) group, PTZ+10 mg/kg SAHA group and PTZ+50 mg/kg SAHA group.Intraperitoneal injection of PTZ was used to induce rat seizure.SAHA was injec-ted intraperitoneally 2 h before PTZ injection.The rats in different seizure stages were counted and mean seizure score was analyzed at 30~60 min after PTZ injection.Hippocampal tissues were sampled at 24 h after seizures.The expression of TLR4, MYD88, NF-κB P65 and IL-1βat mRNA and protein levels was detected by RT-qPCR and Western blot, respec-tively.The pathological changes of the brain tissues were observed by HE staining.The apoptotic neurons were observed by TUNEL staining.RESULTS:The mRNA and protein levels of TLR4, MYD88, NF-κB P65 and IL-1β, the apoptosis of neurons, the inflammation reaction and mean seizure score significantly increased after PTZ treatment (P<0.05), and these effects were attenuated by treatment with SAHA.Compared with PTZ+10 mg/kg SAHA group, PTZ+50 mg/kg SA-HA group showed more significant protective effect against seizure-induced brain damage.CONCLUSION: Histone deacetylase inhibitor SAHA suppresses seizure-induced TLR4/MYD88 signaling and reduces apoptosis of neurons, sugges-ting a protective effect against brain damage associated with seizure in developing rats.
