TY - JOUR
T1 - Inhibitory effects of aripiprazole on interferon-γ-induced microglial activation via intracellular Ca2+ regulation in vitro
AU - Kato, Takahiro
AU - Mizoguchi, Yoshito
AU - Monji, Akira
AU - Horikawa, Hideki
AU - Suzuki, Satoshi O.
AU - Seki, Yoshihiro
AU - Iwaki, Toru
AU - Hashioka, Sadayuki
AU - Kanba, Shigenobu
PY - 2008/7
Y1 - 2008/7
N2 - The activation of the inflammatory/immunological response system is suggested to be related to the pathophysiology of schizophrenia. Aripiprazole is a novel atypical antipsychotic, which is a high-affinity dopamine D2 receptor partial agonist. Atypical antipsychotics, all of which have dopamine D2 receptor antagonism, have recently reported to have significantly inhibitory effects on interferon (IFN)-γ-induced microglial activation in vitro. In the present study, we investigated whether or not aripiprazole also has anti-inflammatory effect on IFN-γ-induced microglial activation. Not quinpirole, dopamine D2 full agonist, but aripiprazole significantly inhibited the generation of nitric oxide (NO) and tumor necrosis factor (TNF)-α from IFN-γ-activated microglia and suppressed the IFN-γ-induced elevation of intracellular Ca2+ concentrations ([Ca2+]i) in murine microglial cells. Increased [Ca2+]i has been reported to be required, but by itself not sufficient, for the release of NO and certain cytokines. As a result, we can speculate that aripiprazole may inhibit IFN-γ-induced microglial activation through the suppression of IFN-γ-induced elevation of [Ca2+]i in microglia. Our results demonstrated that not only antipsychotics which have dopamine D2 receptor antagonism but also aripiprazole have anti-inflammatory effects via the inhibition of microglial activation. Antipsychotics may therefore have a potentially useful therapeutic effect on patients with schizophrenia by reducing the microglial inflammatory reactions.
AB - The activation of the inflammatory/immunological response system is suggested to be related to the pathophysiology of schizophrenia. Aripiprazole is a novel atypical antipsychotic, which is a high-affinity dopamine D2 receptor partial agonist. Atypical antipsychotics, all of which have dopamine D2 receptor antagonism, have recently reported to have significantly inhibitory effects on interferon (IFN)-γ-induced microglial activation in vitro. In the present study, we investigated whether or not aripiprazole also has anti-inflammatory effect on IFN-γ-induced microglial activation. Not quinpirole, dopamine D2 full agonist, but aripiprazole significantly inhibited the generation of nitric oxide (NO) and tumor necrosis factor (TNF)-α from IFN-γ-activated microglia and suppressed the IFN-γ-induced elevation of intracellular Ca2+ concentrations ([Ca2+]i) in murine microglial cells. Increased [Ca2+]i has been reported to be required, but by itself not sufficient, for the release of NO and certain cytokines. As a result, we can speculate that aripiprazole may inhibit IFN-γ-induced microglial activation through the suppression of IFN-γ-induced elevation of [Ca2+]i in microglia. Our results demonstrated that not only antipsychotics which have dopamine D2 receptor antagonism but also aripiprazole have anti-inflammatory effects via the inhibition of microglial activation. Antipsychotics may therefore have a potentially useful therapeutic effect on patients with schizophrenia by reducing the microglial inflammatory reactions.
KW - Atypical antipsychotic drug
KW - Inflammatory cytokine
KW - Intracellular Ca regulation
KW - Microglia
KW - Nitric oxide
KW - Schizophrenia
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U2 - 10.1111/j.1471-4159.2008.05435.x
DO - 10.1111/j.1471-4159.2008.05435.x
M3 - Article
C2 - 18429930
AN - SCOPUS:51649096464
SN - 0022-3042
VL - 106
SP - 815
EP - 825
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 2
ER -