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Assessing Retinal Microglial Phagocytic Function In Vivo Using a Flow Cytometry-based Assay
Published on: October 18, 2016
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Fluoxetine Decreases Phagocytic Function via REV-ERBα in Microglia
Da-Yoon Jang1,2, Bohyun Yang1, Min-Jung You1
1Department of Pharmacology, School of Medicine, Research Institute for Basic Medical Science, CHA University, CHA BIO COMPLEX, 335 Pangyo, Bundang-Gu, Seongnam-si, 13488, Gyeonggi-do, Republic of Korea.
Neurochemical Research
|September 1, 2022
Summary
Fluoxetine (FLX) reduces microglial phagocytosis by accumulating BMAL1 in the cytoplasm via REV-ERBα and ERK signaling pathways. This finding sheds light on the therapeutic mechanisms of this common psychiatric medication.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Fluoxetine (FLX) is widely prescribed for psychiatric disorders, but its precise therapeutic mechanism remains unclear.
- Microglial phagocytosis plays a crucial role in brain function and disease.
- Understanding FLX's impact on microglia is essential for elucidating its neurobiological effects.
Purpose of the Study:
- To investigate the mechanism by which fluoxetine (FLX) influences microglial phagocytic activity.
- To explore the role of REV-ERBα and BMAL1 in FLX-mediated microglial modulation.
- To determine the involvement of the ERK signaling pathway in FLX's effects on microglia.
Main Methods:
- Utilized BV2 cell lines and primary microglia cultures.
- Assessed phagocytic function using standard assays.
- Measured gene and protein expression, including REV-ERBα, BMAL1, and inflammation markers.
- Investigated nucleocytoplasmic transport (NCT) of BMAL1.
- Employed pharmacological inhibitors (SR8278, FR180204) and analyzed phospho-ERK (pERK) levels.
Main Results:
- Fluoxetine (FLX) decreased microglial phagocytic function and increased REV-ERBα expression.
- FLX restricted the nucleocytoplasmic transport (NCT) of BMAL1, causing its accumulation in the cytosol.
- REV-ERBα antagonist SR8278 reversed FLX-induced decreases in phagocytosis and BMAL1 NCT.
- FLX-mediated effects were linked to the inhibition of phospho-ERK (pERK).
- ERK inhibition mimicked FLX's effects on microglial phagocytosis and BMAL1 NCT.
Conclusions:
- Fluoxetine (FLX) reduces microglial phagocytic function through the REV-ERBα pathway.
- FLX inhibits BMAL1 nucleocytoplasmic transport (NCT) via REV-ERBα and ERK signaling.
- These findings provide novel insights into the molecular mechanisms underlying fluoxetine's therapeutic actions in psychiatric disorders.
