Rosiglitazone Exerts an Anti-depressive Effect in Unpredictable Chronic Mild-Stress-Induced Depressive Mice by Maintaining Essential Neuron Autophagy and Inhibiting Excessive Astrocytic Apoptosis.
Rosiglitazone Exerts an Anti-depressive Effect in Unpredictable Chronic Mild-Stress-Induced Depressive Mice by Maintaining Essential Neuron Autophagy and Inhibiting Excessive Astrocytic Apoptosis.
复制标题
罗格列酮通过维持基本神经元自噬和抑制过度星形胶质细胞凋亡，对不可预测的慢性轻度应激诱发的抑郁小鼠发挥抗抑郁作用
DOI：
10.3389/fnmol.2017.00293
复制
发表时间：
2017
影响因子：
4.8
通讯作者：
Sun XL
中科院分区：
文献类型：
--
作者：
Zhao Z;Zhang L;Guo XD;Cao LL;Xue TF;Zhao XJ;Yang DD;Yang J;Ji J;Huang JY;Sun XL
人们越来越关注抑郁症与代谢性疾病发展之间的关系。罗格列酮是一种用于治疗2型糖尿病的治疗药物，在中风和阿尔茨海默病患者中显示出神经保护作用。本研究旨在评价罗格列酮在体内（不可预测的慢性轻度应激诱导的抑郁小鼠模型）和体外（皮质酮诱导的细胞模型）抑郁模型中的可能作用。结果显示，罗格列酮可逆转小鼠强迫游泳和旷场实验的抑郁行为。罗格列酮还被发现抑制炎症反应，降低皮质酮水平，促进小鼠前额叶皮层星形胶质细胞增殖和神经元轴突可塑性。这一系列的体内和体外实验表明，在抑郁模型中，神经元之间的自噬被抑制，罗格列酮通过上调LKB 1促进自噬，从而发挥神经保护作用。还发现罗格列酮通过增加IGF-1 R表达和IGF-1蛋白水平激活Akt/CREB通路，从而在星形胶质细胞中发挥抗凋亡作用。罗格列酮的自噬促进和神经保护作用被原代神经元中的PPARγ拮抗剂T0070907和N2 a细胞系中的PPARγ敲低所逆转。总之，我们发现罗格列酮在体内和体外抑郁模型中都保护神经元和星形胶质细胞，从而发挥抗抑郁作用。这些结果提示，PPARγ可能成为抗抑郁药物开发的新靶点。
There is increasing interest in the association between depression and the development of metabolic diseases. Rosiglitazone, a therapeutic drug used to treat type 2 diabetes mellitus, has shown neuroprotective effects in patients with stroke and Alzheimer’s disease. The present study was performed to evaluate the possible roles of rosiglitazone in in vivo (unpredictable chronic mild stress-induced depressive mouse model) and in vitro (corticosterone-induced cellular model) depressive models. The results showed that rosiglitazone reversed depressive behaviors in mice, as indicated by the forced swimming test and open field test. Rosiglitazone was also found to inhibit the inflammatory response, decrease corticosterone levels, and promote astrocyte proliferation and neuronal axon plasticity in the prefrontal cortex of mice. This series of in vivo and in vitro experiments showed that autophagy among neurons was inhibited in depressive models and that rosiglitazone promoted autophagy by upregulating LKB1, which exerted neuroprotective effects. Rosiglitazone was also found to activate the Akt/CREB pathway by increasing IGF-1R expression and IGF-1 protein levels, thereby playing an anti-apoptotic role in astrocytes. Rosiglitazone’s autophagy promotion and neuroprotective effects were found to be reversed by the PPARγ antagonist T0070907 in primary neurons and by PPARγ knockdown in an N2a cell line. In conclusion, we found that rosiglitazone protects both neurons and astrocytes in in vivo and in vitro depressive models, thereby playing an anti-depressive role. These findings suggest that PPARγ could be a new target in the development of anti-depressive drugs.
登录
查看更多内容
影响因子：
4
作者：
Bonet-Costa, Vicent;Herranz-Perez, Vicente;Vina, Jose
通讯作者：
Vina, Jose
姜黄素和 HU-211 共封装固体脂质纳米粒对皮质酮诱导的重度抑郁症细胞和动物模型的抗抑郁作用
影响因子：
8
作者：
He X;Zhu Y;Wang M;Jing G;Zhu R;Wang S
通讯作者：
Wang S
影响因子：
3.1
作者：
Kahl, Kai G.;Schweiger, Ulrich;Correll, Christoph;Mueller, Conrad;Busch, Marie-Luise;Bauer, Michael;Schwarz, Peter
通讯作者：
Schwarz, Peter
DOI：
10.1098/rstb.1996.0129
发表时间：
1996-10-29
期刊：
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
GoldmanRakic, PS
通讯作者：
GoldmanRakic, PS
影响因子：
120.7
作者：
Golden, Sherita Hill;Lazo, Mariana;Lyketsos, Constantine
通讯作者：
Lyketsos, Constantine