MCC950, a NLRP3 inflammasome inhibitor, prevents radiation-induced cognitive impairment in mice / 中华放射医学与防护杂志

ABSTRACT

Objective:To investigate the effect of MCC950 (a NLRP3 inflammasome inhibitor) on cognitive impairment in mice with radiation-induced inflammatory brain injury.Methods:Mice were divided into normal (NS) group, whole body irradiation (IR) group and MCC950 intervention post irradiation (IR+ MCC950) group according to the random number table method, with 15 mice in each group. The mice in IR group and IR+ MCC950 group were irradiated with a single dose of 4.0 Gy. The radiation source was 137Cs and the dose rate was 1.118 Gy/min. The mice in NS group were not irradiated. Mice in IR+ MCC950 group were injected intraperitoneally with MCC950 once a day (10 mg/kg each time) from 3 weeks after irradiation. Behavioral tests such as new and old things recognition experiment and social cognition experiment were used to detect the cognitive function of mice. Immunohistochemistry was used to detect the expression of NeuN protein in CA3 area of mouse hippocampus. PCR and Western blot were used to detect the expression of NLRP3 inflammatory body related protein. Results:Compared with NS group, the short-term and long-term recognition index of new and old things in the IR group decreased significantly ( t=4.321, 5.473, P<0.01), and the social cognitive recognition index of the IR group also decreased significantly ( t=2.097, P<0.05). MCC950 treatment reversed the above changes (short-term and long-term new and old thing recognition test: t=5.860, 4.598, P<0.05; new and old position recognition test: t=3.040, P<0.05; social cognition test: t=4.021, P<0.01). The expression of NLRP3, Caspase-1, IL-1 β and IL-18 in mice hippocampus of the IR group was significantly higher than that of the control group ( t=2.699, 8.515, 3.340, 3.950, P<0.05). Compared with NS mice, radiation significantly increased the expressions of Bax, Caspase-3 and PARP1 in hippocampus ( t=3.887, 2.742, 3.287, P<0.05), while MCC950 significantly decreased the expressions of Bax, Caspase-3 and PARP1( t=2.852, 4.090, 9.614, P<0.05). Conclusions:NLRP3 inflammasome inhibitor MCC950 could alleviate radiation-induced cognitive impairment, which may be due to the inhibition of hippocampal inflammatory and neuronal death.