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; GUO Lei; PAN San-Qiang

doi:10.16098/j.issn.0529-1356.2021.01.002

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Acta Anatomica Sinica ›› 2021, Vol. 52 ›› Issue (1) : 14-20. DOI: 10.16098/j.issn.0529-1356.2021.01.002

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*

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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.

Key words

Amphetamine / PC12 cell / Dopamine neuron / Protein kinase B / Glycogen synthase kinase 3β / Collapsin response mediator protein 2 / Immunohistochemistry / Mouse

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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

References

［1］ Granado N, Escobedo I, O’Shea E, et al. Early loss of dopaminergic terminals in striosomes after MDMA administration to mice ［J］. Synapse,2008, 62(1): 80-84.
［2］ Cunha-Oliveira T, Rego AC, Oliveira CR. Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs ［J］. Brain Res Rev, 2008, 58(1):192-208.
［3］ He W, Yan X, Pan S. Amphetamine neurotoxicity in PC12 cells through the PP2A/Akt/GSK3β pathway ［J］. Neurotox Res, 2018,34(2), 233-240.
［4］ Mines MA, Jope RS. Brain region differences in regulation of Akt and GSK3 by chronic stimulant administration in mice［J］. Cell Signal, 2012, 24:1398-1405.
［5］ Chen YCh, Guan YJ, Liu YX, et al. Protective role of AKT-glycogen synthase kinase-3β signaling pathway in the N2a cell with SOD1G93Amutation ［J］. Acta Anatomica Sinica, 2016,47(4): 433-441. (in Chinese)
陈燕春, 管英俊, 刘永新, 等. AKT-糖原合成激酶-3β信号通路对SOD1G93A 突变N2a细胞的保护作用［J］. 解剖学报, 2016,47(4): 433-441.
［6］ Wu J, Zhu D, Zhang J, et al. Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway［J］. Biochem Biophys Res Commun, 2015, 465(3):368-373.
［7］ Jiang H, Guo W, Liang X, et al. Both the establishment and the maintenance of neuronal polarity require active mechanisms: critical roles of GSK-3beta and its upstream regulator ［J］. Cell, 2005, 120(1):123-135.
［8］ Sams-Dodd F．Phencyclidine-induced stereotyped behaviour and social isolation in rats: a possible animal model of schizophrenia［J］. Behav Pharmacol, 1996, 7 (1):3-23．
［9］ Hamada N, Fujita Y, Kojima T, et al. MicroRNA expression profiling of NGF-treated PC12 cells revealed a critical role for miR-221 in neuronal differentiation ［J］. Neurochem Int,2012, 60(8):743-750.
［10］ Bowyer JF, Frame LT, Clausing P, et al. longterm effects of amphetamine neurotoxicity on tyrosine hydroxylase mRNA and protein in aged rats ［J］. J Pharmacol Exp Ther, 1998, 286(2):1074-1085.
［11］ Seiden LS, Commins DL, Vosmer G, et al. Neurotoxicity in dopamine and 5-hydroxytryptamine terminal fields: a regional analysis in nigrostriatal and mesolimbic projections ［J］.Ann N Y Acad Sci,1988, 537:161-172.
［12］ Granado N, Escobedo Ⅰ, O’Shea E, et al. Early loss of dopaminergic terminals in striosomes after MDMA administration to mice ［J］. Synapse,2008, 62(1):80-84.
［13］ Büttner A. Review: the neuropathology of drug abuse［J］. Neuropathol Appl Neurobiol, 2011, 37(2):118-134.
［14］ Cunha-Oliveira T, Rego AC, Oliveira CR. Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs［J］. Brain Res Rev, 2008, 58(1): 192-208.
［15］ Fang W, Gao G, Zhao H, et al. Role of AKT/GSK-3β/CRMP-2 pathway in axon degeneration of dopaminergic neurons resulting from MPP+ toxicity ［J］. Brain Res,2015,1602: 9-19.
［16］ Wu Z, Wang G, Wei Y, et al. PI3K/AKT/GSK33β/CRMP-2-mediated neuroplasticity in depression induced by stress ［J］. Neuroreport, 2018, 29(15):1256-1263.
［17］ Liu L, Sun T, Xin F, et al. Nerve growth factor protects against alcoholinduced neurotoxicity in PC12 cells via PI3K/Akt/mTOR pathway ［J］. Alcohol Alcohol, 2017, 52(1):12-18.
［18］ Soligo M, Albini M, Bertoli FL, et al. Different responses of PC12 cells to different pro-nerve growth factor protein variants ［J］.Neurochem Int, 2019, 129:104498.