标题：TLR4-NF-kappa B Signal Involved in Depressive-Like Behaviors and Cytokine Expression of Frontal Cortex and Hippocampus in Stressed C57BL/6 and ob/ob Mice
作者：Wang, Yihe; Xu, Jingjing; Liu, Yuan; Li, Ziyang; Li, Xiaohong
作者机构：[Wang, Yihe] Shandong Univ, Sch Med, Jinan 250012, Shandong, Peoples R China.; [Xu, Jingjing; Liu, Yuan] Shandong Univ, Sch Basic Med Sci, Dept Med 更多
通讯作者地址：[Li, XH]Shandong Univ, Jinan Cent Hosp, Dept Neurol, Jinan 250013, Shandong, Peoples R China.
摘要：Studies found that elevated levels of cytokines such as interleukin- (IL-) 1 beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) are closely associated with the pathogenesis of depression. Obesity providing a low-grade inflammation state was proposed to be implicated in susceptibility to depression in obesity. However, the alterations of cytokines and the TLR4-NF-kappa B signal in the brain of normal weight and obese mice under stress have not been fully elucidated. This study used chronic unpredictable mild stress (CUMS) to induce a depressive-like behavior in an animal model and examine depressive-like behaviors, memory changes, and serum corticosterone levels, as well as the expressions of cytokines and NF-kappa B in the frontal cortex and hippocampus. We aimed to observe the role of neuroinflammation in susceptibility to depression in obesity under CUMS. In addition, we investigated the protective effect of inhibiting the TLR4-NF-kappa B signal. Our results demonstrated that CUMS induced depressive-like behavior and spatial memory damage, higher level of serum corticosterone, and overexpression of cytokines and NF-kappa B in the frontal cortex and hippocampus in both C57BL/6 and ob/ob mice. ob/ob mice displayed serious behavioral disorder and higher levels of IL-1 beta, IL-6, TNF-alpha, and NF-kappa B. Our results concluded that a hyperactive TLR4-NF-kappa B signal and higher level of cytokines are involved in susceptibility to depression in stressed obese mice.