摘要
目的建立精神分裂症的腹侧海马损伤大鼠模型,并探讨模型大脑中蛋白激酶B(PKB/Akt)和叉头型转录因子O亚型(FoxOs)蛋白磷酸化活性水平。方法健康雄性SD乳鼠随机分为2组,腹侧海马损伤组(NVHL)和对照组,每组各8只大鼠,利用脑立体定位技术注射鹅膏蕈氨酸制备腹侧海马损伤模型。第56~60天时,大鼠接受自发活动、前脉冲抑制(PPI)等行为学测试。测试完成3 d后取大鼠脑组织进行形态学观察。采用Western blot测定大鼠皮层和纹状体Akt/FoxOs磷酸化水平。结果与对照组大鼠相比,NVHL大鼠腹侧海马明显损伤。安非他命诱导的自发探索活动增加[(1014±72)次比(753±87)次,P<0.01],PPI受损[PP6:(5.04±3.24)%比(22.08±14.26)%,PP9:(11.26±5.24)%比(25.16±13.45)%,PP12:(8.17±10.45)%比(29.16±10.25)%,均P<0.01]。大脑皮层Akt/FoxO1和纹状体Akt/FoxO1/FoxO3a磷酸化水平降低(P<0.05)。结论腹侧海马损伤是一个广泛应用的精神分裂症动物模型,海马损伤后大鼠皮层和纹状体Akt/FoxOs蛋白磷酸化水平下降,提示该通路参与了精神分裂症的过程。
Objective To establish a rat model of hippocampal injury in schizophrenia,and to investigate the protein phosphorylation activity of protein kinase B(PKB/Akt)and forkhead box Os(FoxOs)protein in the model brain.Methods Healthy male Sprague-Dawley rats were randomly divided into two groups:the neonatal ventral hippocampus lesion(NVHL)and the control group,with 8 rats in each group.The model of NVHL was established by stereotactic injection with ibotenic acid.At 56-60 days,the rats were subjected to spontaneous activity,pre pulse inhibition(PPI)and other behavioral tests.Three days after the test,the brain tissue was taken for morphological observation.Akt/FoxOs phosphorylation levels in cortex and striatum were measured by Western blot.Rusults Compared with the control group,the ventral hippocampus of NVHL rats was significantly damaged.Amphetamine induced spontaneous exploration activity increased[(1014±72)times vs.(753±87)times,P<0.01],PPI was impaired[PP6:(5.04±3.24)%vs.(22.08±14.26)%,PP9:(11.26±5.24)%vs.(25.16±13.45)%,PP12:(8.17±10.45)%vs.(29.16±10.25)%,all P<0.01]in the NVHL group.The phosphorylation levels of Akt/FoxO1 in cerebral cortex and Akt/FoxO1/FOXO3a in striatum were decreased(P<0.05).Conclusions Ventral hippocampal injury is a widely used animal model of schizophrenia.After hippocampal injury,Akt/FoxOs protein phosphorylation levels in cortex and striatum of rats decreased,which further indicated that this pathway was involved in the process of schizophrenia.
作者
白渊翰
曾志文
Bai Yuanhan;Zeng Zhiwen(Department of Bipolar Disorder,Shenzhen Mental Health Center,Shenzhen Kangning Hospital,Shenzhen 518118,China)
出处
《神经疾病与精神卫生》
2020年第11期767-771,共5页
Journal of Neuroscience and Mental Health
基金
国家自然科学基金项目(81701315)
广东省自然科学基金项目(2017A030313769)
广东省高水平临床重点专科(深圳市配套建设经费)资助项目(SZGSP013)
深圳市科技计划项目(JCYJ20170306154944261)
深圳市“医疗卫生三名工程”项目(SZSM201612006)
深圳市医学重点学科建设经费资助项目(SZXK043)。
关键词
精神分裂症
海马损伤模型
蛋白激酶B
叉头型转录因子O亚型
Schizophrenia
Neonatal ventral hippocampal lesion model
Protein kinase B(PKB/Akt)
Forkhead Box Os(FoxOs)
