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Effects of Haloperidol, Risperidone, and Aripiprazole on the Immunometabolic Properties of BV-2 Microglial Cells
Valentino Racki1, Marina Marcelic2, Igor Stimac2
1Department of Neurology, Medical Faculty, University of Rijeka, 51000 Rijeka, Croatia.
Abstract:
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.
Insights
This study shows that antipsychotics haloperidol, risperidone, and aripiprazole reduce pro-inflammatory microglial responses. Aripiprazole uniquely enhances anti-inflammatory markers and reduces mTORC1 activity, suggesting a novel mechanism.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Microglial cells, the brain's immune cells, play a role in schizophrenia.
- The impact of antipsychotics on microglial function remains unclear, with limited research on their anti-inflammatory mechanisms.
Purpose of the Study:
- To investigate the in vitro effects of haloperidol, risperidone, and aripiprazole on BV-2 microglial cells.
- To characterize the impact of these antipsychotics on microglial inflammatory markers, metabolic function, and mTOR pathway activity.
Main Methods:
- Immunofluorescence and flow cytometry were used to analyze pro- and anti-inflammatory markers.
- Real-time metabolic assays (Seahorse) assessed cellular metabolic function.
- Western blot analyzed mTOR pathway activity via p70S6K expression.
Main Results:
- All tested antipsychotics (haloperidol, risperidone, aripiprazole) reduced pro-inflammatory microglial actions.
- Aripiprazole was unique in increasing anti-inflammatory marker expression.
- Significant differences were observed in metabolic function and mTORC1 pathway activity, with aripiprazole reducing mTORC1 activity.
Conclusions:
- Haloperidol, risperidone, and aripiprazole exhibit varying effects on microglial cells.
- Aripiprazole demonstrates a distinct mechanism of action, potentially through mTORC1 inhibition, offering new insights into its therapeutic effects.
