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小鼠顶叶皮层反复轻度创伤性脑损伤抑制延髓NLG-1和PSD-95的表达OA北大核心CSTPCDMEDLINE

Repeated mild traumatic brain injury in the parietal cortex inhibits expressions of NLG-1 and PSD-95 in the medulla oblongata of mice

中文摘要英文摘要

目的 研究反复轻度创伤性脑损伤(rmTBI)对延髓神经元形态和突触可塑性的影响.方法 32只雄性ICR小鼠随机分为假手术组(SHAM组,n=8)和rmTBI组(n=24).使用自由落体打击装置建立rmTBI模型,打击后存活小鼠为rmTBI存活组(rmTBI-S),打击后死亡小鼠为rmTBI死亡组(rmTBI-D).使用神经损伤评分、翻正反射和强迫游泳实验检测小鼠神经功能障碍,使用苏木素-伊红及尼氏染色观察神经细胞病理形态改变,使用免疫印迹及免疫荧光染色检测神经连接蛋白1(NLG-1)和突触后致密蛋白95(PSD-95)表达水平.结果 SHAM组小鼠无死亡,rmTBI组死亡率41.67%,差异有统计学意义(P<0.05);和SHAM组相比,rmTBI-S组小鼠神经损伤评分降低(P<0.001)、翻正反射恢复时间(P<0.001)和强迫游泳不动时间(P<0.05)增加,神经元尼氏小体消失、肿胀坏死;延髓NLG-1(P<0.05)和PSD-95(P<0.05)表达水平降低;和rmTBI-S组相比,rmTBI-D组NLG-1(P<0.01)和PSD-95(P<0.01)表达水平降低.rmTBI-D组小鼠延髓神经纤维扭曲水肿,神经元密度降低.结论 延髓突触结构异常和功能障碍可能与rmTBI导致的死亡及神经功能损害相关.

Objective To assess the effects of repeated mild traumatic brain injury(rmTBI)in the parietal cortex on neuronal morphology and synaptic plasticity in the medulla oblongata of mice.Methods Thirty-two male ICR mice were randomly divided into sham operation group(n=8)and rmTBI group(n=24).The mice in the latter group were subjected to repeated mild impact injury of the parietal cortex by a free-falling object.The mice surviving the injuries were evaluated for neurological deficits using neurological severity scores(NSS),righting reflex test and forced swimming test,and pathological changes of the neuronal cells in the medulla oblongata were observed with HE and Nissl staining.Western blotting and immunofluorescence staining were used to detect the expressions of neuroligin 1(NLG-1)and postsynaptic density protein 95(PSD-95)in the medulla oblongata of the mice that either survived rmTBI or not.Results None of the mice in the sham-operated group died,while the mortality rate was 41.67%in rmTBI group.The mice surviving rmTBI showed significantly reduced NSS,delayed recovery of righting reflex,increased immobility time in forced swimming test(P<0.05),and loss of Nissl bodies;swelling and necrosis were observed in a large number of neurons in the medulla oblongata,where the expression levels of NLG-1 and PSD-95 were significantly downregulated(P<0.05).The mice that did not survive rmTBI showed distorted and swelling nerve fibers and decreased density of neurons in the medulla oblongina with lowered expression levels of NLG-1 and PSD-95 compared with the mice surviving the injuries(P<0.01).Conclusion The structural and functional anomalies of the synapses in the medulla oblongata may contribute to death and neurological impairment following rmTBI in mice.

李明明;何梁超;李天雨;鲍岩;徐祥;陈光

皖南医学院法医学院,安徽 芜湖 241000

反复轻度创伤性脑损伤;延髓;神经连接蛋白-1;突触后致密蛋白-95;突触可塑性

repeated mild traumatic brain injury;medulla oblongata;neuroligin 1;postsynaptic density protein 95;synaptic plasticity

《南方医科大学学报》 2024 (005)

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安徽省高等学校自然科学研究重点项目(2022AH051222);安徽省大学生创新创业训练计划项目(S202210368010);法医病理学公安部重点实验室开放课题(GAFYBL202306);皖南医学院中青年科研基金(WK2023ZQNZ19)

10.12122/j.issn.1673-4254.2024.05.18

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