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Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells

Microglial cells are resident macrophages in the brain that have been implicated in the pathophysiology of schizophrenia. There is a lack of studies covering the effects of antipsychotics on microglial cells. The current literature points to a possible anti-inflammatory action without clear mechanis...

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Autores principales: Racki, Valentino, Marcelic, Marina, Stimac, Igor, Petric, Daniela, Kucic, Natalia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122792/
https://www.ncbi.nlm.nih.gov/pubmed/33922377
http://dx.doi.org/10.3390/ijms22094399
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author Racki, Valentino
Marcelic, Marina
Stimac, Igor
Petric, Daniela
Kucic, Natalia
author_facet Racki, Valentino
Marcelic, Marina
Stimac, Igor
Petric, Daniela
Kucic, Natalia
author_sort Racki, Valentino
collection PubMed
description Microglial cells are resident macrophages in the brain that have been implicated in the pathophysiology of schizophrenia. There is a lack of studies covering the effects of antipsychotics on microglial cells. The current literature points to a possible anti-inflammatory action without clear mechanisms of action. The aim of this study is to characterize the effects of haloperidol, risperidone and aripiprazole on BV-2 microglial cells in in vitro conditions. We have used immunofluorescence and flow cytometry to analyze the classical pro and anti-inflammatory markers, while a real-time metabolic assay (Seahorse) was used to assess metabolic function. We analyzed the expression of p70S6K to evaluate the mTOR pathway activity with Western blot. In this study, we demonstrate the varying effects of haloperidol, risperidone and aripiprazole administration in BV-2 microglial cells. All three tested antipsychotics were successful in reducing the pro-inflammatory action of microglial cells, although only aripiprazole increased the expression of anti-inflammatory markers. Most significant differences in the possible mechanisms of action were seen in the real-time metabolic assays and in the mTORC1 signaling pathway activity, with aripiprazole being the only antipsychotic to reduce the mTORC1 activity. Our results shed some new light on the effects of haloperidol, risperidone and aripiprazole action in microglial cells, and reveal a novel possible mechanism of action for aripiprazole.
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spelling pubmed-81227922021-05-16 Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells Racki, Valentino Marcelic, Marina Stimac, Igor Petric, Daniela Kucic, Natalia Int J Mol Sci Article Microglial cells are resident macrophages in the brain that have been implicated in the pathophysiology of schizophrenia. There is a lack of studies covering the effects of antipsychotics on microglial cells. The current literature points to a possible anti-inflammatory action without clear mechanisms of action. The aim of this study is to characterize the effects of haloperidol, risperidone and aripiprazole on BV-2 microglial cells in in vitro conditions. We have used immunofluorescence and flow cytometry to analyze the classical pro and anti-inflammatory markers, while a real-time metabolic assay (Seahorse) was used to assess metabolic function. We analyzed the expression of p70S6K to evaluate the mTOR pathway activity with Western blot. In this study, we demonstrate the varying effects of haloperidol, risperidone and aripiprazole administration in BV-2 microglial cells. All three tested antipsychotics were successful in reducing the pro-inflammatory action of microglial cells, although only aripiprazole increased the expression of anti-inflammatory markers. Most significant differences in the possible mechanisms of action were seen in the real-time metabolic assays and in the mTORC1 signaling pathway activity, with aripiprazole being the only antipsychotic to reduce the mTORC1 activity. Our results shed some new light on the effects of haloperidol, risperidone and aripiprazole action in microglial cells, and reveal a novel possible mechanism of action for aripiprazole. MDPI 2021-04-22 /pmc/articles/PMC8122792/ /pubmed/33922377 http://dx.doi.org/10.3390/ijms22094399 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Racki, Valentino
Marcelic, Marina
Stimac, Igor
Petric, Daniela
Kucic, Natalia
Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells
title Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells
title_full Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells
title_fullStr Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells
title_full_unstemmed Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells
title_short Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells
title_sort effects of haloperidol, risperidone, and aripiprazole on the immunometabolic properties of bv-2 microglial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122792/
https://www.ncbi.nlm.nih.gov/pubmed/33922377
http://dx.doi.org/10.3390/ijms22094399
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