期刊
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
卷 45, 期 6, 页码 525-535出版社
WILEY
DOI: 10.1111/1440-1681.12918
关键词
inflammation-related depression; JNK; p38; neural apoptosis; PI3K; AKT; pioglitazone
资金
- National Key R&D Program of China [2017YFA0505700]
- Outstanding Young Scholars in Chongqing Medical University [CYYQ201502]
- National Natural Science Foundation of China [81601208]
Numerous studies have reported that inflammation is involved in the pathophysiology of depression. Pioglitazone, a PPAR- 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 (20mg/kg, intragastrically) attenuated LPS-induced (10ng/L per site) depressive-like behaviours. GW9662, a PPAR- antagonist, significantly blocked the antidepressant-like effect of pioglitazone. Furthermore, at the molecular level, pioglitazone significantly reversed, via PPAR--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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据