摘要
目的探讨重复经颅磁刺激(rTMS)对双环己酮草酰二腙(CPZ)诱导的精神分裂症小鼠认知损伤的改善作用及内源性大麻素受体1(CB1R)、二酰基甘油脂肪酶(DAGLα)、N酰基磷脂酰乙醇胺磷脂酶D(NAPE-PLD)、脂肪酰胺水解酶(FAAH)和单酰基甘油脂肪酶(MAGL)表达的影响.方法将24只C57BL/6小鼠随机分为对照组(sham)、模型组(CPZ)、模型+rTMS治疗组(CPZ+rTMS),每组8只.CPZ+rTMS组和CPZ组小鼠饲喂含有0.2%CPZ的饲料6周后,分别接受7 d的rTMS(5 Hz,1.26 Tesla)或假刺激;sham组正常饲喂6周并接受7 d的rTMS假刺激.最后一次rTMS干预结束24 h后进行Y迷宫和三箱社交测试;随后处死动物,取海马组织进行蛋白质印迹实验,检测其内源性大麻素相关基因的蛋白表达变化.结果与sham组相比,CPZ组表现出明显的空间记忆损伤和社交缺陷,包括Y迷宫实际交替进臂百分比下降[sham组(62.69±7.92)%比CPZ组(43.78±14.30)%,P<0.01]和三箱社交实验中与2处陌生小鼠接触时间减少[sham组(233.41±3.84)比(157.02±63.62)s,P<0.05;CPZ组(164.30±79.16)比(249.28±58.31)s,P<0.05].与sham组小鼠相比,CPZ组小鼠海马的CB1R、DAGLα和NAPE-PLD蛋白表达下调[(1.14±0.09)比(0.77±0.13)、(0.76±0.12)比(0.38±0.10)、(0.81±0.12)比(0.36±0.11),P<0.05],而FAAH表达上调[(0.73±0.09)比(1.14±0.16),P<0.05].rTMS干预可以改善CPZ小鼠的空间记忆损伤和社交缺陷,CPZ+rTMS组小鼠在Y迷宫测试中的实际交替进臂百分比较CPZ组上调[CPZ组(43.78±14.30)%比CPZ+rTMS组(60.40±10.62)%,P<0.05)];三箱社交实验中,CPZ+rTMS组小鼠与2处陌生小鼠接触时间更长[(236.74±51.66)比(158.41±68.45)s,P<0.05].rTMS干预可以恢复CPZ小鼠海马的内源性大麻素相关基因表达水平,CPZ+rTMS组小鼠海马的CB1R、DAGLα、FAAH和NAPE-PLD蛋白水平[(1.13±0.11)、(0.68±0.13)、(0.66±0.08)、(0.64±0.14)]与CPZ组比较,差异均有统计学意义(P<0.05).结论rTMS可以改善CPZ诱导的精神分裂症小鼠模型的认知损伤�
Objective To investigate the effect of repetitive transcranial magnetic stimulation(rTMS)on cognitive impairment and the expression of endocannabinoid system-related genes,including CB1R(cannabinoid receptor1),DAGLα(Diacylglycerol-α),NAPE-PLD(N acylphosphatidyl ethanolamin phospholipase D), FAAH (Fatty acid amide hydrolase) and MAGL (monoacylglycerol) in the hippocampus incuprizone (CPZ)-induced mice model of schizophrenia. Methods A total of 24 C57BL/6 mice were randomlyassigned to the following 3 groups (n=8 for each group): sham, CPZ and CPZ + rTMS. The mice in the CPZ +rTMS and CPZ group were administered 0.2% CPZ in standard powdered rodent chow for 6 weeks, then receivedrTMS treatment (5 Hz, 1.26T) or sham rTMS treatment for 7 days;concurrently, the mice in sham group werefed with normal powdered rodent chow for 6 weeks, and then received sham rTMS treatment for 7 days. 24 hoursafter the completion of the last rTMS intervention, mice were subjected to Y-maze and 3-chamber tests. Thenthe mice were sacrificed, and Western blot was used to detect the protein expression of cannabinoid relatedgenes in hippocampus. Results Compared with sham group, CPZ group showed significant spatial memoryimpairment and social deficits, including decreased percentages of spontaneous alternations in Y maze test [sham(62.69±7.92)% vs CPZ (43.78±14.30)%, P < 0.01], and less duration with stranger in the 3-chamber test[sham: (233.41±3.84) vs (157.02±63.62), P<0.05);CPZ: (164.30±79.16) vs (249.28±58.31) s,P< 0.05)].Compared with sham group, the expression levels of CB1R, DAGLα and NAPE-PLD in hippocampus ofthe CPZ group was decreased [(1.14±0.09) vs (0.77±0.13), (0.76±0.12) vs (0.38±0.10), (0.81±0.12)vs (0.36±0.11), P < 0.05], while expression of FAAH of the CPZ group was increased [(0.73±0.09) vs(1.14±0.16), P < 0.05]. rTMS treatment improved cognitive impairment and social deficits in mice exposedto CPZ, evidenced by increased percentages of spontaneous alternations in Y maze test in CPZ+rTMS groupthan in CPZ grou
作者
于欢
薛姗姗
赵建帅
王莹
赵洁玉
谭庆荣
周翠红
Yu Huan;Xue Shanshan;Zhao Jianshuai;Wang Ying;Zhao Jieyu;Tan Qingrong;Zhou Cuihong(Department of Psychiatry,the First Affiliated Hospital of Air Force Military Medical University,Xi'an 710032,China;Department of Anesthesiolog,the First Affiliated Hospital of Air Force Military Medical University,Xi'an 710032,China)
出处
《神经疾病与精神卫生》
2021年第8期533-539,共7页
Journal of Neuroscience and Mental Health
基金
国家自然科学基金项目(81904280,81630032,81671343)。
关键词
精神分裂症
重复经颅磁刺激
海马
内源性大麻素
Schizophrenia
Repetitive transcranial magnetic stimulation
Hippocampus
Endocannabinoid
