Deng Zhifang, Yuan Cheng, Yang Jian, Peng Yan, Wang Wei, Wang Yan, Gao Wenqi
Department of Pharmacy, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang 443000, China.
Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China.
Ann Transl Med. 2019 Jan;7(1):6. doi: 10.21037/atm.2018.12.08.
The aim of this study was to evaluate the protective effects of polysaccharides (MCP) on depressive-like behaviors.
The chronic social defeat stress (CSDS) mice model was used to evaluate the effects of MCP and their underlying mechanisms. Social interaction test (SIT), sucrose preference test (SPT), and tail suspension test (TST) were performed for behavioral assessments. Expression levels of inflammation mediators and phosphatidylinositol 3-kinase (PI3K) activity were determined using commercial ELISA kits. The expression of key proteins in the c-Jun N-terminal protein kinase (JNK3)/PI3K/protein kinase B (AKT) pathway were measured using western blot and RT-PCR.
The results showed that chronic administration of MCP (100, 200, 400 mg/kg/day) significantly prevented depressive-like behaviors in CSDS mice as assessed by SIT, TST and SPT. Elevated levels of proinflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β)], and expression of JNK3, c-Jun, P-110β proteins were observed in the hippocampus of CSDS mice. Moreover, the activity of PI3K and phosphorylation level of AKT were reduced in the hippocampus of CSDS mice. Interestingly, the administration of MCP reversed these changes. Furthermore, the protective effects of MCP on CSDS mice were partly inhibited by the PI3K inhibitor, LY294002.
In conclusion, the protective effects of MCP against depressive-like behaviors in CSDS mice might be due to a reduction in neuroinflammation and the down-regulation of the JNK3/PI3K/AKT pathway in the hippocampus.
本研究旨在评估多糖（MCP）对抑郁样行为的保护作用。
采用慢性社会挫败应激（CSDS）小鼠模型评估MCP的作用及其潜在机制。进行社会互动测试（SIT）、蔗糖偏好测试（SPT）和悬尾测试（TST）以进行行为评估。使用商用ELISA试剂盒测定炎症介质的表达水平和磷脂酰肌醇3激酶（PI3K）活性。使用蛋白质免疫印迹法和逆转录聚合酶链反应（RT-PCR）检测c-Jun氨基末端蛋白激酶（JNK3）/PI3K/蛋白激酶B（AKT）通路中关键蛋白的表达。
结果显示，通过SIT、TST和SPT评估，慢性给予MCP（100、200、400mg/kg/天）可显著预防CSDS小鼠的抑郁样行为。在CSDS小鼠海马中观察到促炎细胞因子[肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）]水平升高，以及JNK3、c-Jun、P-110β蛋白的表达。此外，CSDS小鼠海马中PI3K的活性和AKT的磷酸化水平降低。有趣的是，给予MCP可逆转这些变化。此外，PI3K抑制剂LY294002部分抑制了MCP对CSDS小鼠的保护作用。
总之，MCP对CSDS小鼠抑郁样行为的保护作用可能是由于神经炎症的减少以及海马中JNK3/PI3K/AKT通路的下调。
