Abstract
Astrocyte is considered to be a type of passive supportive cells that preserves neuronal activity and survival. The dysfunction of astrocytes is involved in the pathological processes of major depression. Recent studies implicate sigma-1 receptors as putative therapeutic targets for current available antidepressant drugs. However, it is absent of direct evidences whether sigma-1 receptor could promote activation of astrocyte. In the present study, we took advantage of primary astrocyte culture and a highly selective agonist of sigma-1 receptor, (+)SKF-10047 to determine the effect of sigma-1 receptor on Brdu (bromodeoxyuridine) labeling positive cells, migration as well as GFAP (glial fibrillary acidic protein) expression of astrocyte. The results showed that (+)SKF-10047 notably increased the number of Brdu labeling positive cells, migration, and the expression of GFAP in primary astrocytes, which were blocked by antagonist of sigma-1 receptor. Moreover, we also found that (+)SKF-10047 increased the phosphorylation of ERK1/2 (extracellular signal-regulated kinases 1/2) and GSK3β (glycogen synthase kinase 3β) (ser 9) in the primary astrocytes. In addition, pharmacological inhibition of ERK1/2 and GSK3β (ser 9) abolished sigma-1 receptor-promoted activation of astrocyte. Therefore, sigma-1 receptor could be considerate as a new pattern for modulating astrocytic function might emerge as therapeutic strategies.
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10 November 2021
A Correction to this paper has been published: https://doi.org/10.1007/s00210-021-02180-5
Abbreviations
- MAM:
-
Mitochondrion-associated ER membranes
- GFAP:
-
Glial fibrillary acidic protein
- ERK1/2:
-
Extracellular signal-regulated kinases 1/2
- GSK3β:
-
Glycogen synthase kinase 3β
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Funding
This work was supported by the National Natural Science Foundation of China (81603086), the project funded by China Postdoctoral Science Foundation (2016M601894), the Postgraduate Scientific Research and Innovation Project of Jiangsu Province (1701052A), Science and Technology Planning Project of Xuzhou (KC18047), and Fund of Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy (ZR-XY201504).
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LG designed and wrote the manuscript. YW, JN, and FHJ performed the experiments and analyzed the data.
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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors. All animal experiments were performed in accordance with the Guide for the Care and Use of Laboratory Animals by the National Institutes of Health (USA) and approved by the Research Ethics Committee of Xuzhou Medical University.
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Figure S
Effect of sigma-1 receptor activation on phosphorylation of AKT (ser 473) in the primary astrocytes. (+)SKF-10047 rapidly increased the phosphorylation of AKT (ser 437, 40 min), which was blocked by LY293004 (50 μM, 30 min) pretreatment (two-way ANOVA). Data were expressed as mean ± SEM, each experiment was replicated three times. (PNG 46 kb)
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Wang, Y., Jiang, Hf., Ni, J. et al. Pharmacological stimulation of sigma-1 receptor promotes activation of astrocyte via ERK1/2 and GSK3β signaling pathway. Naunyn-Schmiedeberg's Arch Pharmacol 392, 801–812 (2019). https://doi.org/10.1007/s00210-019-01632-3
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DOI: https://doi.org/10.1007/s00210-019-01632-3