Effects of Atypical Antipsychotics, Clozapine, Quetiapine and Brexpiprazole on Astroglial Transmission Associated with Connexin43
Abstract
:1. Introduction
2. Results
2.1. Effects of Mood-Stabilizing Antipsychotics on Astroglial l-Glutamate Release
2.1.1. Concentration-Dependent Effects of Acute and Subchronic Administration of Mood-Stabilizing Antipsychotics on Astroglial l-glutamate Release during Resting Stage (Study-1)
2.1.2. Interaction between Subchronic Administration of Therapeutic-Relevant Concentration of Valproate (VPA) and Acute Administration of Antipsychotics on l-Glutamate Release through Activated Hemichannel (Study-2)
2.1.3. Interaction between Subchronic Administrations of Therapeutic-Relevant Concentration of VPA and Antipsychotics on l-Glutamate Release through Activated Hemichannel (Study-3)
2.1.4. Effects of Cx43 Inhibitor on Astroglial l-glutamate Release through Activated Hemichannel Enhanced by Acute Administration of Antipsychotics (Study-4)
2.1.5. Effects of Acute Administration of Protein Kinase B (Akt) Inhibitor on Astroglial l-glutamate Release through Activated Hemichannel Enhanced by Acute and Subchronic Administration of Antipsychotics, after the Subchronic Administration of Therapeutic-Relevant Concentration of VPA (Study-5)
2.2. Effects of Mood-Stabilizing Antipsychotics on Expression of Cx43 Protein in the Astroglial Plasma Membrane Fraction
2.2.1. Effects of Subchronic Administration of Therapeutic-Relevant Concentrations of Antipsychotics alone on Cx43 Expression in the Plasma Membrane Fraction
2.2.2. Effects of Acute and Subchronic Administrations of Therapeutic-Relevant Concentration of Antipsychotics on Cx43 Expression in the Astroglial Plasma Membrane, after Subchronic Administration of Therapeutic-Relevant Concentration of VPA
3. Discussion
3.1. Mechanisms of Mood-Stabilizing Antipsychotics, CLZ, QTP and BPZ, on Astroglial l-Glutamate Release through Hemichannel
3.2. Mechanisms of Clinical Action of Mood-Stabilizing Antipsychotics Associated with Cx43
4. Materials and Methods
4.1. Chemical Agents
4.2. Preparation of Primary Astrocyte Culture
4.3. Ultra-High-Performance Liquid Chromatography (UHPLC)
4.4. Capillary Immunoblotting Analysis
4.5. Data Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Administration | CLZ | QTP | BPZ | Figure | |
---|---|---|---|---|---|
Astroglial glutamate release | |||||
Basal glutamate release | Acute (120 min) | ↑ | → | → | Figure 1 |
Subchronic (7 days) | → | → | → | Figure 1 | |
Evoked glutamate release | Acute (120 min) | ↑↑ | ↑ | ↑ | Figure 2 |
Subchronic (7 days) | ↑↑ | ↑↑ | ↑↑ | Figure 3 | |
Evoked release | Acute (120 min) | ↑↑ | ↑↑ | ↑↑ | Figure 2 |
(+subchronic VPA) | Subchronic (7 days) | ↑↑ | ↑↑ | ↑↑ | Figure 3 |
Akt inhibitor sensitivity of glutamate release | |||||
Evoked release | Acute (120 min) | ↓ | → | → | Figure 5 |
(+ subchronic VPA) | Subchronic (7 days) | ↓ | ↓ | → | Figure 5 |
Cx43 expression in the astroglial plasma membrane | |||||
(+ subchronic VPA) | Acute (120 min) | ↑↑ | → | → | Figure 7 |
(+ subchronic VPA) | Subchronic (7 days) | ↑↑ | ↑↑ | ↑↑ | Figure 7 |
Akt sensitivity of Cx43 expression in the astroglial plasma membrane | |||||
(+ subchronic VPA) | Acute (120 min) | ↓↓ | → | → | Figure 7 |
(+ subchronic VPA) | Subchronic (7 days) | ↓↓ | ↓↓ | → | Figure 7 |
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Fukuyama, K.; Okada, M. Effects of Atypical Antipsychotics, Clozapine, Quetiapine and Brexpiprazole on Astroglial Transmission Associated with Connexin43. Int. J. Mol. Sci. 2021, 22, 5623. https://doi.org/10.3390/ijms22115623
Fukuyama K, Okada M. Effects of Atypical Antipsychotics, Clozapine, Quetiapine and Brexpiprazole on Astroglial Transmission Associated with Connexin43. International Journal of Molecular Sciences. 2021; 22(11):5623. https://doi.org/10.3390/ijms22115623
Chicago/Turabian StyleFukuyama, Kouji, and Motohiro Okada. 2021. "Effects of Atypical Antipsychotics, Clozapine, Quetiapine and Brexpiprazole on Astroglial Transmission Associated with Connexin43" International Journal of Molecular Sciences 22, no. 11: 5623. https://doi.org/10.3390/ijms22115623