Amphetamine causing damage of dopamine cells via inhibiting of protein kinase B / glycogen synthase kinase-3β/ collapsin response mediator protein-2 signal pathway
10.16098/j.issn.0529-1356.2021.01.002
- Author:
Ya-Li REN
1
;
Ya-Li REN
2
;
Lei GUO
2
;
San-Qiang PAN
2
Author Information
1. Department of Nursing, Jiyuan Vocational and Technical College
2. Department of Anatomy, Medical School of Jinan University
- Publication Type:Journal Article
- Keywords:
Amphetamine;
Collapsin response mediator protein 2;
Dopamine neuron;
Glycogen synthase kinase 3β;
Immunohistochemistry;
Mouse;
PC12 cell;
Protein kinase B
- From:
Acta Anatomica Sinica
2021;52(1):14-20
- CountryChina
- Language:Chinese
-
Abstract:
Objective To 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.
