苯丙胺通过抑制蛋白激酶B/糖原合成酶激酶3β/脑衰蛋白反应介导蛋白2信号通路损伤多巴胺神经细胞

任亚丽; 郭磊; 潘三强

doi:10.16098/j.issn.0529-1356.2021.01.002

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解剖学报 ›› 2021, Vol. 52 ›› Issue (1) : 14-20. DOI: 10.16098/j.issn.0529-1356.2021.01.002

神经生物学

苯丙胺通过抑制蛋白激酶B/糖原合成酶激酶3β/脑衰蛋白反应介导蛋白2信号通路损伤多巴胺神经细胞

任亚丽^1,2 郭磊² 潘三强^2*

作者信息 +

Amphetamine causing damage of dopamine cells via inhibiting of protein kinase B/glycogen synthase kinase-3β/collapsin response mediator protein-2 signal pathway

REN Ya-li^1,2 GUO Lei² PAN San-qiang^2*

Author information +

文章历史 +

摘要

目的探讨苯丙胺损伤多巴胺神经细胞的信号通路机制。方法通过腹腔注射苯丙胺建立小鼠多巴胺细胞损伤模型，将小鼠随机分为正常组、生理盐水组、苯丙胺1 d组、7 d组、14 d组和28 d组，每组10只。在PC12细胞中加入苯丙胺建立细胞损伤模型。通过免疫组织化学和免疫荧光技术观察小鼠纹状体多巴胺神经纤维和PC12细胞的变化，通过免疫印迹法检测纹状体和PC12细胞蛋白激酶B（Akt）/糖原合成酶激酶3β(GSK-3β)/脑衰蛋白反应介导蛋白2(CRMP-2)通路蛋白的变化。结果苯丙胺损伤小鼠纹状体多巴胺神经纤维和PC12细胞的突起，并引起磷酸化Akt（p-Akt）和磷酸化GSK-3β（p-GSK-3β）表达减少，磷酸化CRMP-2（p-CRMP-2）表达增多。给予Akt上游的激活剂神经生长因子和GSK-3β的抑制剂SB216763，则增加p-Akt和p-GSK-3β的表达，抑制p-CRMP-2的表达，并且对PC12细胞的突起有保护作用。结论抑制Akt/GSK-3β/CRMP-2信号通路是苯丙胺损伤多巴胺神经细胞的机制之一。

Abstract

ObjectiveTo explore the damage mechanism of dopamine cells induced by amphetamine (AMPH). Methods The damage model of dopaminergic cells in mice was established by intraperitoneal injection of AMPH. The mice were randomly grouped into control, saline, amphetamine treatment for 1 day, 7 days, 14 days and 28 days. Each group contained 10 mice. The model of cell injury was established by use of AMPH in PC12 cells. The dopaminergic fibers of corpus striatum and PC12 cells were observed by the immunohistochemistry and immunofluorescence method , and changes of proteins in the protein kinase B (Akt)/glycogen synthase kinase 3β(GSK-3β)/collapsin response mediator protein 2 (CRMP-2) signal pathway were detected by Western blotting. Results AMPH caused the damage of dopaminergic fibers in the mouse corpus striatum and PC12 cells. Meanwhile, AMPH inhibited Akt and GSK-3β phosphorylation levels, and increased phosphorylated CRMP-2 level. Nerve growth factor(NGF), an agonist of Akt, or SB216763, an inhibitor of GSK-3β protected PC12 cells against AMPH-induced toxicity through upregulation of Aat and GSK-3β phosphorylation and downregulated of phosphorylation CRMP-2.

Conclusion AMPH causes damage of dopamine cells via inhibition of Akt/GSK-3β/CRMP-2 signal pathway.

导出引用

任亚丽郭磊潘三强. 苯丙胺通过抑制蛋白激酶B/糖原合成酶激酶3β/脑衰蛋白反应介导蛋白2信号通路损伤多巴胺神经细胞[J]. 解剖学报. 2021, 52(1): 14-20 https://doi.org/10.16098/j.issn.0529-1356.2021.01.002

REN Ya-li GUO Lei PAN San-qiang. Amphetamine causing damage of dopamine cells via inhibiting of protein kinase B/glycogen synthase kinase-3β/collapsin response mediator protein-2 signal pathway[J]. Acta Anatomica Sinica. 2021, 52(1): 14-20 https://doi.org/10.16098/j.issn.0529-1356.2021.01.002

中图分类号： R395.3 R741.02

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