PI3K/AKT/JNK/p38 signalling pathway-mediated neural apoptosis in the prefrontal cortex of mice is involved in the antidepressant-like effect of pioglitazone
Jie Li
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorBing Xu
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorZhi Chen
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorChanjuan Zhou
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorLi Liao
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, China
Search for more papers by this authorYinghua Qin
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, China
Search for more papers by this authorChuangchuang Yang
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorXiaodong Zhang
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorZicheng Hu
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorLin Sun
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorDan Zhu
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorCorresponding Author
Peng Xie
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China
Correspondence
Peng Xie, Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Email: [email protected]
Search for more papers by this authorJie Li
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorBing Xu
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorZhi Chen
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorChanjuan Zhou
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorLi Liao
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, China
Search for more papers by this authorYinghua Qin
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, China
Search for more papers by this authorChuangchuang Yang
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorXiaodong Zhang
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorZicheng Hu
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorLin Sun
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorDan Zhu
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorCorresponding Author
Peng Xie
Chongqing Key Laboratory of Neurobiology, Chongqing, China
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China
Correspondence
Peng Xie, Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Email: [email protected]
Search for more papers by this authorSummary
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 LY294002, a PI3K/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. GW9662, 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 PI3K/AKT pathway and down-regulation of the JNK/p38 pathway. Moreover, both anisomycin and LY294002 abrogated the antidepressant-like effect of pioglitazone.; In conclusion, our results showed that PI3K/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.
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