Aripiprazole inhibits polyI:C-induced microglial activation possibly via TRPM7
| Autor: | Mina Sato-Kasai, Shigenobu Kanba, Akira Monji, Yoshihiro Seki, Sota Kyuragi, Noriaki Sagata, Kohei Hayakawa, Yoshito Mizoguchi, Takahiro A. Kato, Shogo Inamine, Hideki Horikawa, Masahiro Ohgidani, Norihiro Shimokawa |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine MAPK/ERK pathway Cations Divalent MAP Kinase Signaling System p38 mitogen-activated protein kinases Aripiprazole TRPM Cation Channels Protein Serine-Threonine Kinases Pharmacology p38 Mitogen-Activated Protein Kinases 03 medical and health sciences 0302 clinical medicine TRPM7 medicine Animals Humans RNA Messenger Protein kinase A Cells Cultured Biological Psychiatry Microglia Tumor Necrosis Factor-alpha Chemistry Anti-Inflammatory Agents Non-Steroidal Brain In vitro Mice Inbred C57BL Psychiatry and Mental health Poly I-C 030104 developmental biology medicine.anatomical_structure Immunology Calcium Tumor necrosis factor alpha 030217 neurology & neurosurgery Antipsychotic Agents medicine.drug |
| Zdroj: | Schizophrenia Research. 178:35-43 |
| ISSN: | 0920-9964 |
| DOI: | 10.1016/j.schres.2016.08.022 |
| Popis: | Viral infections during fetal and adolescent periods, as well as during the course of schizophrenia itself have been linked to the onset and/or relapse of a psychosis. We previously reported that the unique antipsychotic aripiprazole, a partial D2 agonist, inhibits the release of tumor necrosis factor (TNF)-α from interferon-γ-activated rodent microglial cells. Polyinosinic-polycytidylic acid (polyI:C) has recently been used as a standard model of viral infections, and recent in vitro studies have shown that microglia are activated by polyI:C. Aripiprazole has been reported to ameliorate behavioral abnormalities in polyI:C-induced mice. To clarify the anti-inflammatory properties of aripiprazole, we investigated the effects of aripiprazole on polyI:C-induced microglial activation in a cellular model of murine microglial cells and possible surrogate cells for human microglia. PolyI:C treatment of murine microglial cells activated the production of TNF-α and enhanced the p38 mitogen-activated protein kinase (MAPK) pathway, whereas aripiprazole inhibited these responses. In addition, polyI:C treatment of possible surrogate cells for human microglia markedly increased TNF-α mRNA expression in cells from three healthy volunteers. Aripiprazole inhibited this increase in cells from two individuals. PolyI:C consistently increased intracellular Ca2+ concentration ([Ca2+]i) in murine microglial cells by influx of extracellular Ca2+. We demonstrated that transient receptor potential in melastatin 7 (TRPM7) channels contributed to this polyI:C-induced increase in [Ca2+]i. Taken together, these data suggest that aripiprazole may be therapeutic for schizophrenia by reducing microglial inflammatory reactions, and TRPM7 may be a novel therapeutic target for schizophrenia. Further studies are needed to validate these findings. |
| Databáze: | OpenAIRE |
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