Tauroursodeoxycholic Acid Ameliorates Lipopolysaccharide-Induced Depression Like Behavior in Mice via the Inhibition of Neuroinflammation and Oxido-Nitrosative Stress

Abstract

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.

p-Cresol Sulfate Caused Behavior Disorders and Neurodegeneration in Mice with Unilateral Nephrectomy Involving Oxidative Stress and Neuroinflammation

“…Although there were limitations, the current findings still highlighted a potential contribution of PCS in the development of depression in this rodent model. The etiology of depression is multifactorial, including genetic, environmental, and dietary factors, particularly chronic stress and diseases [ 5 , 6 , 26 , 28 ]. Accumulating evidence highlights the pathogenic roles of oxidative stress, neuroinflammation, impaired neurogenesis, as well as dysregulated neurotransmitters and neurohormonal pathways in the development and progression of depression [ 6 , 23 , 24 , 25 , 29 ].…”

“…CNS diseases are accompanied by a series of biochemical and molecular changes, resulting in acute and long-term impacts on both behavioral and neurological functions. Changes in blood–brain barrier permeability, oxidative stress, neuroinflammation, neurochemicals, neurotrophins, neurogenesis, apoptosis, and synaptic connection are frequently presented in most neurological diseases [ 5 , 6 ]. In rodent models with CKD caused by adenine feeding or a 5/6 nephrectomy, the experimental animals have shown depression- and anxiety-like behaviors concurrent with an impaired blood–brain barrier and the cerebral activation of oxidative stress and neuroinflammation.…”

“…Those studies suggest that depression and/or anxiety may be the most vulnerable neurological complications of CKD [ 7 , 8 , 9 ]. CKD and CNS diseases share many commonalities, particularly oxidative stress and inflammation [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. The integration of CKD alterations is believed to promote both the transition and pathogenesis for the development of neurological diseases.…”

Lipopolysaccharide-Induced Depression-Like Behaviors Is Ameliorated by Sodium Butyrate via Inhibiting Neuroinflammation and Oxido-Nitrosative Stress

“…Mechanistic studies have revealed that the increased proinflammatory cytokine can trigger oxido-nitrosative stress, a pathological event that could be observed in depressed patients, thereby promoting depression onset and/or progression [15][16][17][18][19]. Previous studies have also found that hippocampus and prefrontal cortex are the key regions of the brain, closely associated with mood and behavior regulation [20,21], and more importantly many compounds that are being studied in preclinical trials have been shown to ameliorate depression-like behaviors in rodents via interfering with neuroinflammatory response and oxido-nitrosative stress in the hippocampus and prefrontal cortex [10,11,22]. Therefore, suppression of neuroinflammation and oxido-nitrosative stress, especially in the hippocampus and prefrontal cortex, may be a potential strategy for depression treatment.…”

Effect and related mechanism of Yinchenhao decoction on mice with lithogenic diet‑induced cholelithiasis

“…Finally, the filtered liquids were concentrated under pressure at 60˚C and stored at 4˚C. tauroursodeoxycholic acid (TUDCA) is a water-soluble bile acid that is commonly used in clinical settings (30) and was provided by Bruschettini S.R.L. TUDCA was used as the positive control drug in the present study.…”