Abstract
BackgroundThe accumulated evidence demonstrates that stress plays an important role in the pathogenesis of depression that is associated with intestinal dysfunctions. However, the mechanisms remain unresolved.MethodsA total of 40 male Wistar rats were obtained and randomly divided into four equal-sized group: control, PDTC + chronic and unpredictable mild stress (CUMS), FLX + CUMS, and CUMS. Western blotting and qRT-PCR were used to examine the levels of nitric oxide (NO), nuclear factor kappa beta (NF-κB), inducible nitric oxide synthase (iNOS), and iNOS mRNA in spinal cord L1-2 and colon.Key ResultsChronic and unpredictable mild stress increased the serum CORT level, decreased body weight and sucrose preference, and altered OFT performance, while increased levels of NO, iNOS mRNA, iNOS and NF-κB protein in colon and spinal cord were accompanied by histopathological changes in colon. Pretreatment with an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), reversed these effects. Fluoxetine failed to prevent NO increase in both spinal cord and colon, while the iNOS protein level, although not statistically significantly increased compared to control, was not decreased compared to CUMS. Also, fluoxetine failed to prevent histological changes.ConclusionIn conclusion, the NF-κB/iNOS pathway may be involved in the mechanism of CUMS-induced depressive-like behavior and colon tissue injury.
Highlights
It has been documented that neuropsychiatric disorders are closely associated with dysfunctions of the gut (Zhao et al, 2018)
We aimed to investigate the effects of PDTC, an inhibitor of NF-κB, and fluoxetine, as a positive control, on behavioral changes, body weight, and colon tissue as well as to explore the mechanism of chronic and unpredictable mild stress (CUMS)-induced colon tissue injury in depressive rats
The results indicated that CUMS was able to enhance the production of NO in both spinal cord and colon and that inhibition of NF-κB signaling could prevent CUMS-induced production of NO, suggesting that the excessive production of NO is downstream of NF-κB signaling in response to CUMS
Summary
It has been documented that neuropsychiatric disorders are closely associated with dysfunctions of the gut (Zhao et al, 2018). Ample clinical studies show that the prevalence of mental disorders, especially depression and anxiety, in patients with gastrointestinal (GI) symptoms is approximately 80% (Kurina et al, 2001). Cognitive-behavioral therapy and antidepressants have been confirmed to alleviate the symptoms of patients with GI disorders (Wiley et al, 2016). It is well known that stress is an important factor in the genesis of neuropsychiatric disorders (Gulati et al, 2015). The mechanisms of dysfunctions in the gut that are induced by stress-associated conditions are poorly understood. The accumulated evidence demonstrates that stress plays an important role in the pathogenesis of depression that is associated with intestinal dysfunctions.
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