engineering-human-blood-induced-microglia-like-cells-for-reverse

Engineering of Human Blood-Induced Microglia-like Cells for Reverse-Translational Brain Research

Recent investigations employing animal models have highlighted the significance of microglia as crucial immunological modulators in various ...

Kyushu University

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 Ca concentration ([Ca]) in murine microglial cells by influx of extracellular Ca. We demonstrated that transient receptor potential in melastatin 7 (TRPM7) channels contributed to this polyI:C-induced increase in [Ca]. 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.

Aripiprazole inhibits polyI:C-induced microglial activation possibly via TRPM7.

A case of bipolar disorder with AIF1 (coding gene of Iba-1) deletion: A pilot in vitro analysis using blood-derived microglia-like cells.

High-sensitivity C-reactive protein and bilirubin as possible biomarkers for hikikomori in depression: A case-control study.

In the 1990s, the concepts of hikikomori and modern-type depression (MTD) emerged in Japan. Hikikomori is a condition of social avoidance or isolation, characterized by staying at home and being physically isolated for at least six months. MTD is characterized by depressive symptoms-mainly in stressful work or school situations during adolescence and early adulthood-which tend to rapidly reduce or disappear after leaving the stressful situation. We hypothesized that childhood maltreatment can form MTD traits that lead to hikikomori.

Sota Kyuragi

Department of Neuropsychiatry,
Graduate School of Medical Sciences,
Department of Neuropsychiatry, Graduate School of Medical Sciences

Kyushu University

Engineering of Human Blood-Induced Microglia-like Cells for Reverse-Translational Brain Research

Sota Kyuragi

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Neuropsychiatry,Graduate School of Medical Sciences,Department of Neuropsychiatry, Graduate School of Medical Sciences

Kyushu University

Engineering of Human Blood-Induced Microglia-like Cells for Reverse-Translational Brain Research

Department of Neuropsychiatry,
Graduate School of Medical Sciences,
Department of Neuropsychiatry, Graduate School of Medical Sciences