慢性束缚抑郁症小鼠模型的癫痫诱发实验

Induction of Epileptic Seizures in Mouse Models of Chronic Restraint Stress

目的观察抑郁症模型小鼠对癫痫诱发条件的敏感性。方法采用随机数字表法将雄性C57BL/6J小鼠随机分为慢性束缚(CRS)组(建立CRS抑郁小鼠模型)和正常对照(NC)组,采用糖水偏爱实验和强迫游泳实验评估抑郁症模型的建立情况。分别给两组小鼠经腹腔注射海人酸,通过视频记录小鼠的癫痫发作行为,包括:起始时间、癫痫发作评分、癫痫发作次数和癫痫发作的持续时间,并在两组间进行比较。结果 CRS组小鼠在水中的不动时间为(120. 9±13. 5) s,明显长于NC组的(59. 1±9. 8) s (t=3. 700,P=0. 0019,);在0～24 h和0～48 h的糖水消耗比例分别为(64. 7±4. 7)%和(73. 3±3. 0)%,明显低于NC组的(77. 2±2. 5)%(t=2. 672,P=0. 0167)和(83. 0±2. 8)%(t=2. 386,P=0. 0297)。CRS组小鼠的起始时间为(138±26) s,明显短于NC组小鼠的(234±28) s (t=2. 485,P=0. 0274);两组小鼠的癫痫总发作次数差异无统计学意义[(11. 5±1. 1)次比(13. 7±2. 1)次; t=0. 9767,P=0. 3465];CRS组小鼠的癫痫发作评分为(66±10)分,明显高于NC组的(37±5)分(t=2. 777,P=0. 0157); CRS组小鼠的癫痫发作持续时间为(61±16) min,明显长于NC组的(37±5) min (t=3. 342,P=0. 0053)。结论在相同剂量海人酸注射下,CRS抑郁症小鼠具有更加严重的癫痫发作表型。

Objective To investigate the sensitivity of mouse models of chronic restraint stress to conditions that induce epileptic seizures.Methods Male C57BL/6J mice were randomized into chronic restraint stress(CRS)group and normal control(NC)group.The modeling results were evaluated by sucrose preference test and forced swimming test.Kainic aicd(KA)was intraperitoneally injected to induce acute seizures.Seizure onset time,duration,and scores were recorded and compared.Results During the forced swimming test,the immobility time was(120.9±13.5)s in CRS group and only(59.1±9.8)s in NC group(t=3.700,P=0.0019).During the sucrose preference test,the water consumption proportion at 0-24 h and 0-48 h were(64.7±4.7)%and(73.3±3.0)%,respectively,in CRS group,significantly lower than those[(77.2±2.5)%(t=2.672,P=0.0167)and(83.0±2.8)%(t=2.386,P=0.0297)]in NC group.Although there was no significant difference in the total number of acute seizures[(11.5±1.1)times vs.(13.7±2.1)times;t=0.9767,P=0.3465],mice in CRS group had significantly higher severe seizure score than in control group[(66±10)scores vs.(37±5)scores;t=2.777,P=0.0157].The seizure onset time was(138±26)s in CRS group,which was significantly shorter than that in NC group[(234±28)s;t=2.485,P=0.0274].The seizure duration of the CRS group was(61±16)min,which was significantly longer than that of the NC group[(37±5)min;t=3.342,P=0.0053].Conclusion CRS mice are more susceptible to KA-induced acute epileptic seizures.