Effects of BD1047, a σ1 receptor antagonist, on the expression of mTOR, Camk2γ and GSK‑3β in fluvoxamine‑treated N2a cells

Su,Dong-An; Jiang,Ri-Yue; Liu,Ning; Ding,Liang-Cai; Wang,Da-Ming; Yu,Hai-Ying; Yan,En-Shi; Zhu,Mei-Hua; Zhu,Bin

doi:10.3892/etm.2013.1438

2014-February Volume 7 Issue 2

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2014-February Volume 7 Issue 2

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Article

Effects of BD1047, a σ1 receptor antagonist, on the expression of mTOR, Camk2γ and GSK‑3β in fluvoxamine‑treated N2a cells

Authors:
- Dong-An Su
- Ri-Yue Jiang
- Ning Liu
- Liang-Cai Ding
- Da-Ming Wang
- Hai-Ying Yu
- En-Shi Yan
- Mei-Hua Zhu
- Bin Zhu
View Affiliations / Copyright

Affiliations: Department of Anesthesiology, The PLA 102nd Hospital, Second Military Medical University, Changzhou, Jiangsu 213003, P.R. China, Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China, Department of Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China, Department of Psychiatry, The PLA 102nd Hospital, Second Military Medical University, Changzhou, Jiangsu 213003, P.R. China, Department of Anesthesiology, Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Pages: 435-438
|
Published online on: December 5, 2013

https://doi.org/10.3892/etm.2013.1438
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Abstract

Fluvoxamine, a common antidepressant agent, is designed to exert its pharmacological effect by inhibiting synaptic serotonin reuptake. However, increasing evidence has demonstrated that σ1 receptors are likely to be involved in the mechanism of action of fluvoxamine. The present study aimed to observe the effects of fluvoxamine on the expression levels of mammalian target of rapamycin (mTOR), Ca2+/calmodulin‑dependent protein kinase 2γ (Camk2γ) and glycogen synthase kinase‑3β (GSK‑3β) in fluvoxamine‑treated N2a cells and attempted to elucidate whether σ1 receptors mediate the pharmacological effects of fluvoxamine. The N2a cells were randomly divided into three groups (each n=6): DMEM group (D group), 0.5 µmol/l fluvoxamine group (F group) and 0.2 µmol/l BD1047 (a σ1 receptor antagonist) + 0.5 µmol/l fluvoxamine group (BF group). Western blotting was used to determine the expression levels of mTOR, Camk2γ and GSK‑3β in the cultured N2a cells after two days of incubation. The F group exhibited significant increases in the expression levels of mTOR and Camk2γ and a significant reduction in the expression levels of GSK‑3β compared with those in the D group (P<0.01). By contrast, the BF group demonstrated significant reductions in the expression levels of mTOR and Camk2γ and a significant increase in the expression levels of GSK‑3β, compared with those in the F group (P<0.01). These results suggest that σ1 receptors mediate fluvoxamine‑elicited changes in the expression levels of mTOR, Camk2γ and GSK‑3β in N2a cells, which indicates that σ1 receptors are likely to be involved in the pharmacological effects of fluvoxamine.

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1	Sugimoto Y, Tagawa N, Kobayashi Y, Mitsui-Saito K, Hotta Y and Yamada J: Involvement of the sigma1 receptor in the antidepressant-like effects of fluvoxamine in the forced swimming test in comparison with the effects elicited by paroxetine. Eur J Pharmacol. 696:96–100. 2012. View Article : Google Scholar : PubMed/NCBI
2	Niitsu T, Iyo M and Hashimoto K: Sigma-1 receptor agonists as therapeutic drugs for cognitive impairment in neuropsychiatric diseases. Curr Pharm Des. 18:875–883. 2012. View Article : Google Scholar : PubMed/NCBI
3	Hindmarch I and Hashimoto K: Cognition and depression: the effects of fluvoxamine, a sigma-1 receptor agonist, reconsidered. Hum Psychopharmacol. 25:193–200. 2010. View Article : Google Scholar : PubMed/NCBI
4	Hayashi T and Su TP: An update on the development of drugs for neuropsychiatric disorders: focusing on the sigma 1 receptor ligand. Expert Opin Ther Targets. 12:45–58. 2008. View Article : Google Scholar : PubMed/NCBI
5	Romieu P, Martin-Fardon R, Bowen WD and Maurice T: Sigma 1 receptor-related neuroactive steroids modulate cocaine-induced reward. J Neurosci. 23:3572–3576. 2003.PubMed/NCBI
6	Matsumoto RR, McCracken KA, Pouw B, Zhang Y and Bowen WD: Involvement of sigma receptors in the behavioral effects of cocaine: evidence from novel ligands and antisense oligodeoxynucleotides. Neuropharmacology. 42:1043–1055. 2002. View Article : Google Scholar : PubMed/NCBI
7	Gebreselassie D and Bowen WD: Sigma-2 receptors are specifically localized to lipid rafts in rat liver membranes. Eur J Pharmacol. 493:19–28. 2004. View Article : Google Scholar : PubMed/NCBI
8	Niitsu T, Fujisaki M, Shiina A, et al: A randomized, double-blind, placebo-controlled trial of fluvoxamine in patients with schizophrenia: a preliminary study. J Clin Psychopharmacol. 32:593–601. 2012. View Article : Google Scholar : PubMed/NCBI
9	Collina S, Gaggeri R, Marra A, et al: Sigma receptor modulators: a patent review. Expert Opin Ther Pat. 23:597–613. 2013. View Article : Google Scholar : PubMed/NCBI
10	Iyo M, Shirayama Y, Watanabe H, et al: Fluvoxamine as a sigma-1 receptor agonist improved cognitive impairments in a patient with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 32:1072–1073. 2008. View Article : Google Scholar : PubMed/NCBI
11	Kitagishi Y, Kobayashi M, Kikuta K and Matsuda S: Roles of PI3K/AKT/GSK3/mTOR pathway in cell signaling of mental illnesses. Depress Res Treat. 2012:7525632012.PubMed/NCBI
12	Li X and Jope RS: Is glycogen synthase kinase-3 a central modulator in mood regulation? Neuropsychopharmacology. 35:2143–2154. 2010. View Article : Google Scholar : PubMed/NCBI
13	Tombes RM, Faison MO and Turbeville JM: Organization and evolution of multifunctional Ca²⁺/CaM-dependent protein kinase genes. Gene. 322:17–31. 2003. View Article : Google Scholar : PubMed/NCBI
14	Strenge K, Schauer R and Kelm S: Binding partners for the myelin-associated glycoprotein of N2A neuroblastoma cells. FEBS Lett. 444:59–64. 1999. View Article : Google Scholar : PubMed/NCBI
15	Björkdahl C, Sjögren MJ, Winblad B and Pei JJ: Zinc induces neurofilament phosphorylation independent of p70 S6 kinase in N2a cells. Neuroreport. 16:591–595. 2005.PubMed/NCBI
16	Apter A, Ratzoni G, King RA, et al: Fluvoxamine open-label treatment of adolescent inpatients with obsessive-compulsive disorder or depression. J Am Acad Child Adolesc Psychiatry. 33:342–348. 1994. View Article : Google Scholar : PubMed/NCBI
17	Chen A, Xiong LJ, Tong Y and Mao M: Neuroprotective effect of brain-derived neurotrophic factor mediated by autophagy through the PI3K/Akt/mTOR pathway. Mol Med Rep. 8:1011–1016. 2013.PubMed/NCBI
18	Li N, Lee B, Liu RJ, et al: mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science. 329:959–964. 2010. View Article : Google Scholar : PubMed/NCBI
19	Jernigan CS, Goswami DB, Austin MC, et al: The mTOR signaling pathway in the prefrontal cortex is compromised in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 35:1774–1779. 2011. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Effects of BD1047, a σ1 receptor antagonist, on the expression of mTOR, Camk2γ and GSK‑3β in fluvoxamine‑treated N2a cells

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