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Dexamethasone Induces a Specific Form of Ramified Dysfunctional Microglia

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Abstract

The functional status of dynamic microglial cells plays an important role in maintaining homeostasis of microenvironment in CNS. In a previous study, we reported that microglia phenotype might be involved in stress vulnerability and depression recurrence. Here, we aimed to clarify a character of microglia exposed persistently to glucocorticoid (GC), which is representative a stress hormone, in primary cultured microglial cells. Five nanomolars of dexamethasone (DEX, GC agonist) for 72 h decreased CX3CR1 and CD200R expression and induced ramified form of microglial cells in similar morphology to in vivo resident microglia. However, the ramified form of microglia did not increase microglia signature genes such as P2RY12, OLFML3, TMEM119, and TGFBR1. In addition, DEX-treated microglia showed a reduction of phagocytosis function, pro-and anti-inflammatory cytokine production, and cell proliferation. DEX washout did not restore these changes. Based on transcriptomic analysis and functional characters of DEX-treated microglia, we performed senescence-associated beta-galactosidase (SA-β gal) assay in DEX-treated microglia and DEX-treated microglia showed more SA-β gal activity with alteration of cell cycle-related genes. Thus, our results suggest that DEX can induce a specific phenotype of microglia (like-senescence).

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Funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2017R1D1A1B03029554).

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Author notes

  1. Min-Jung Park and Hyun-Sun Park contributed equally to this study.

Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, CHA University, CHABIOCOMPLEX, 335 Pangyo, Bundang-gu, Seongnam-si, Gyeonggi-do, 13488, Republic of Korea

    Min-Jung Park, Hyun-Sun Park, Min-Jung You & Min-Soo Kwon

  2. Department of Microbiology and School of Medicine, CHA University, CHABIOCOMPLEX, 335 Pangyo, Bundang-gu, Seongnam-si, Gyeonggi-do, 13488, Republic of Korea

    Jongman Yoo

  3. Cell Therapy Center and Department of Neurology, College of Medicine, Hanyang University, Haengdang-dong, Seoul, Republic of Korea

    Seung Hyun Kim

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  1. Min-Jung Park
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Correspondence to Min-Soo Kwon.

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Park, MJ., Park, HS., You, MJ. et al. Dexamethasone Induces a Specific Form of Ramified Dysfunctional Microglia. Mol Neurobiol 56, 1421–1436 (2019). https://doi.org/10.1007/s12035-018-1156-z

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  • DOI: https://doi.org/10.1007/s12035-018-1156-z

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