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• W2787431387 abstract "Summary Numerous studies have reported that inflammation is involved in the pathophysiology of depression. Pioglitazone, a PPAR ‐γ agonist, has potential anti‐inflammatory and antidepressive effects. However, the underlying molecular mechanisms of the antidepressant‐like effect of pioglitazone on an inflammation‐related mouse model of depression remain to be fully elucidated. Herein, we aimed to explore the effects of pioglitazone on depressive‐like behaviours of mice exposed to lipopolysaccharides ( LPS ), and elucidate the underlying mechanisms. We assessed behaviour changes of mice pretreated with pioglitazone exposed to LPS . Additionally, neural apoptosis, and the expression of apoptosis‐related (cleaved caspase‐3, Bax, Bcl‐2, cyt c) and signalling proteins ( AKT , JNK , p38) were assessed in the prefrontal cortex ( PFC ) of these mice. Furthermore, we assessed the influence of anisomycin, a JNK /p38 agonist, and LY 294002, a PI 3K/ AKT inhibitor, on the antidepressant‐like effect of pioglitazone in mice. We show that pioglitazone pretreatment (20 mg/kg, intragastrically) attenuated LPS ‐induced (10 ng/μL per site) depressive‐like behaviours. GW 9662, a PPAR ‐γ antagonist, significantly blocked the antidepressant‐like effect of pioglitazone. Furthermore, at the molecular level, pioglitazone significantly reversed, via PPAR ‐γ‐dependent increase in neural apoptosis in the PFC of mice, accompanied by upregulation of the PI 3K/ AKT pathway and down‐regulation of the JNK /p38 pathway. Moreover, both anisomycin and LY 294002 abrogated the antidepressant‐like effect of pioglitazone.; In conclusion, our results showed that PI 3K/ AKT / JNK /p38 signalling pathway‐mediated neural apoptosis in the PFC of mice may be involved in the antidepressant‐like effect of pioglitazone. This provides novel insights into and therapeutic targets for inflammation‐related depression." @default.
• W2787431387 created "2018-02-23" @default.
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• W2787431387 date "2018-03-07" @default.
• W2787431387 modified "2023-10-13" @default.
• W2787431387 title "<scp>PI</scp>3K/<scp>AKT</scp>/<scp>JNK</scp>/p38 signalling pathway‐mediated neural apoptosis in the prefrontal cortex of mice is involved in the antidepressant‐like effect of pioglitazone" @default.
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• W2787431387 doi "https://doi.org/10.1111/1440-1681.12918" @default.
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