Effect of NLRP3/GSDMD/IL-1β pathway in post epileptic depressive behavior of developmental rats and its possible intervention approaches / 解放军医学杂志

ABSTRACT

Objective To investigate the effect of NLRP3/GSDMD/IL-1β pathway in post epileptic depressive behavior of developmental rats and its possible intervention approaches. Methods Sixty SD male rats aged 21 days were randomly divided into negative Control group, status epilepticus (SE) group, and SE+Dexamethasone (SE+DEX) group (20 each). The temporal lobe epilepsy (TLE) model was established by intraperitoneal injection of Lithium chloride-Pilocarpine (Licl-Pilocarpine) in SE group and SE+DEX group, the SE+DEX group was intraperitoneally injected with DEX [3 mg/(kg·d)] after the convulsion ceased for 7 consecutive days. Rats in SE group and Control group were given the same amount of normal saline at the same time point and by the same way. The post epileptic depressive behavior of rats was evaluated by sucrose partiality test (SPT), open field test (OPT) and forced swimming test (FST, n=8). Western blotting and RT-qPCR were used to detect the expression levels of protein and mRNA of NLRP3 and GSDMD in the hippocampus (n=3), and the expression level of IL-1β in the hippocampus was detected by ELISA (n=3). Results Compared with control group, the sucrose consumption rate decreased (68.50%±8.65% vs. 87.13%±3.31%), the time spent in the central area of the open field was reduced [(1.25±0.55) s vs. (4.73±2.57) s], the total movement distance decreased [(7.34±1.48) cm vs. (11.01±1.94) cm], while the immobility time (IMT) in water increased [(53.74±22.54) s vs. (27.18±11.86) s] in SE group; Compared with SE group, the sucrose consumption rate increased (78.8%±2.80% vs. 68.50%±8.65%), the time spent in the central area of the open field was prolonged [(4.00±2.35) s vs. (1.25±0.55) s], while the IMT was reduced [(22.85±7.85) s vs. (53.74±22.54) s] in SE+DEX group. All the differences were statistically significant (P<0.05). The expression levels of protein and mRNA of NLRP3 and GSDMD, as well as the IL-1β content, were significantly higher in SE group than in Control group (P<0.05); While the expression level of mRNA of NLRP3 was lower in SE+DEX group than in SE group (1.40±0.66 vs. 2.70±0.22, P<0.05), but no obviously difference between the two groups on the expression level of NLRP3 protein, The expression levels of GSDMD protein and mRNA were lower in SE+DEX group than in SE group (0.38±0.11 vs. 0.72±0.03, 1.14±0.44 vs. 1.80±0.08), the IL-1β content was also lower than that in SE group [(299.44±119.35) pg/ml vs. (571.37±18.48) pg/ml] with statistically significant difference (P<0.05). Conclusions NLRP3/GSDMD/IL-1β may be involved in the occurrence and development of epilepsy with depression. Short course intervention with dexamethasone may improve epileptic related depressive behavior in developmental rats by down-regulating GSDMD/IL-1β expression.