Tauroursodeoxycholic Acid Ameliorates Lipopolysaccharide-Induced Depression Like Behavior in Mice via the Inhibition of Neuroinflammation and Oxido-Nitrosative Stress.
Depression is a mental disease that causes severe economic and social burdens. The mechanism for the onset of depression remains largely unknown. Recently, more and more attention is being given to the role of neuroinflammation and oxidative stress in depression. Tauroursodeoxycholic acid (TUDCA), a clinically available agent used to treat cholesterol gallstone and protect neurons against neurodegeneration, has been reported to prevent neuroinflammation and oxidative stress. In this study, we investigated the effect of TUDCA on lipopolysaccharide (LPS)-induced depression-like behavior, neuroinflammation, and oxido-nitrosative stress in mice. Results showed that TUDCA pretreatment (once daily for 7 consecutive days) at the dosage of 200 and 400 mg/kg, but not 100 mg/kg, markedly attenuated LPS (0.83 mg/kg)-induced behavioral abnormalities in the tail suspension test, forced swim test, and sucrose preference test. Further analysis showed that the TUDCA pretreatment (200, 400 mg/kg) not only inhibited the production of proinflammatory cytokines induced by LPS stimulation, such as interleukin-6 and tumor necrosis factor-α, but attenuated LPS-triggered oxido-nitrosative stress in the hippocampus and prefrontal cortex. Taken together, our results provide evidence to show that the TUDCA could be a potential antidepressant, and its antidepressive mechanism may be associated with the inhibition of the neuroinflammatory response and oxido-nitrosative stress in the brain.
['Cheng|Li|L|', 'Huang|Chao|C|', 'Chen|Zhuo|Z|']
D000818:Animals D000928:Antidepressive Agents D016207:Cytokines D003863:Depression D004195:Disease Models, Animal D005473:Fluoxetine D006624:Hippocampus D007249:Inflammation D015850:Interleukin-6 D008070:Lipopolysaccharides D008297:Male D051379:Mice D008813:Mice, Inbred ICR D000073039:Nitrosative Stress D018384:Oxidative Stress D017397:Prefrontal Cortex D013655:Taurochenodeoxycholic Acid D014409:Tumor Necrosis Factor-alpha
Tauroursodeoxycholic acid Depression Neuroinflammation Oxido-nitrosative stress Lipopolysaccharide