scholarly journals Effects of N-Acetylcysteine on Noise Exposure Induced Oxidative Stress and Depressive- and Anxiety-Like Behaviors in Adult Male Mice

Author(s):  
Yavar Mahmoodzadeh ◽  
◽  
Javad Mahmoudi ◽  
Sattar Gorgani-firuzjaee ◽  
Naser Mohtavinejad ◽  
...  

Background: Depression and anxiety are the most common psychiatric disorders that widely occur in industrial societies and severely affect individual's lives. N-acetylcysteine (NAC) is a mucolytic compound with antioxidant and anti-inflammatory effects. This study aimed to investigate the potential therapeutic effects of NAC against chronic noise-induced depression- and anxiety-like behaviors in mice. Methods: Fifty male BALB/c mice were randomly divided into 5 groups: control, noise90 dB, noise110 dB, noise 90+NAC, and noise 110+NAC groups. Animals in the noise groups were exposed to the 90 and 110 dB 2 h/day for 30 days. NAC groups received NAC (325 mg/kg P.O.) 20 min after being exposed to noise. To evaluate depressive- and anxiety-like behaviors, mice were subjected to open field test (OFT), sucrose preference test (SPT), tail suspension test (TST), and elevated plus maze (EPM) tasks. At the end of the behavioral tests, animals were sacrificed and levels of malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were determined in the hippocampus (HIP) and the prefrontal cortex (PFC). Results: The results showed that exposure to noise would induce anxiety- and depressive-like behaviors, being reversed by NAC administration. Moreover, chronic administration of NAC resulted in a significant increase in antioxidant enzyme activities and reduced lipid peroxidation (MDA levels) in the PFC and HIP of noise-exposed mice. Conclusion: Our findings revealed that the administration of NAC would reduce the adverse effects of noise on the brain and would exert anti-depressant and anxiolytic effects.

Author(s):  
Yosuke Kanno ◽  
Kaho Tsuchida ◽  
Chihiro Maruyama ◽  
Kyoko Hori ◽  
Hanako Teramura ◽  
...  

Abstract Objectives Depression is a psychiatric disorder that affects about 10% of the world’s population and is accompanied by anxiety. Depression and anxiety are often caused by various stresses. However, the etiology of depression and anxiety remains unknown. It has been reported that alpha2-antiplasmin (α2AP) not only inhibits plasmin but also has various functions such as cytokine production and cell growth. This study aimed to determine the roles of α2AP on the stress-induced depression and anxiety. Methods We investigated the mild repeated restraint stress-induced depressive and anxiety-like behavior in the α2AP+/+ and α2AP−/− mice using the social interaction test (SIT), sucrose preference test (SPT), and elevated plus maze (EPM). Results The stresses such as the mild repeated restraint stress suppressed α2AP expression in the hippocampus of mice, and the treatment of fluoxetine (selective serotonin reuptake inhibitor [SSRI]) recovered the stress-caused α2AP suppression. We also showed that α2AP deficiency promoted the mild restraint stress-stimulated depression-like behavior such as social withdrawal and apathy and apoptosis in mice. In contrast, α2AP deficiency attenuated the mild restraint stress induced the anxiety-like behavior in mice. Conclusions α2AP affects the pathogenesis of depression and anxiety induced by stress.


2017 ◽  
Vol 10 (1) ◽  
pp. 40-43 ◽  
Author(s):  
Kristina Belovicova ◽  
Eszter Bogi ◽  
Kristina Csatlosova ◽  
Michal Dubovicky

AbstractAn animal model of human behavior represents a complex of cognitive and/or emotional processess, which are translated from animals to humans. A behavioral test is developed primarily and specifically to verify and support a theory of cognition or emotion; it can also be used to verify a theory of a psychopathology, but it is not developed for a particular type of psychopathology. The paper reviews tests commonly used in novel drug discovery research. Focus is especially on tests which can evaluate anxiety-like (open-field test, novelty suppressed feeding, elevated plus maze, light/dark box, stressinduced hyperthermia) and depression-like behaviors (forced swim test, tail suspension test, sucrose preference test) as they represent an important methodological tool in pre-clinical as well as in behavioral toxicology studies.


2019 ◽  
Vol 20 (1) ◽  
pp. 195 ◽  
Author(s):  
Jiawei Wu ◽  
Tingting Zhang ◽  
Luping Yu ◽  
Shuai Huang ◽  
Yu Yang ◽  
...  

Major depressive disorder is now becoming a common disease in daily life, and most patients do not have satisfactory treatment outcomes. We herein evaluated the therapeutic effects of Zhile capsule and clarified the molecular mechanism. A rat model of chronic unpredictable mild stress-induced depression was established to assess the antidepressant-like effects of Zhile by using the sucrose preference test, open field test, forced swim test, tail suspension test and HPLC. Systems pharmacology was then performed to unravel the underlying mechanism which was confirmed by western blot, enzyme-linked immunosorbent assay, and qPCR. Zhile alleviated depression-like behaviors by upregulating the cAMP-CREB-BDNF (brain-derived neurotrophic factor) axis to exert neuroprotective effects. It may be beneficial to depressive patients in clinical practice.


Author(s):  
Jessica MacGregor

gene in humans have been shown to predict non-responsiveness to antidepressant drugs; suggesting that FGF2 is required for antidepressants to work. In this study, we hypothesized that antidepressants will not work in rodents that lack the FGF2 gene. Hence, we tested antidepressant treatment in transgenic mice that had the FGF2 gene knocked out. Chronic unpredictable stress (CUS) has been used for several decades to produce a reliable depressive and anxious phenotype in mice. This study followed a CUS paradigm and used fluoxetine (Prozac) as antidepressant treatment. Mice received daily fluoxetine administration beginning on week three of CUS and continued until the end of week five to provide an antidepressant effect and reverse the effects of stress. To test for levels of anxiety and depression, a battery of behavioral tests was conducted which began from the least stressful (i.e. sucrose preference test, open field maze, elevated plus maze) to the most stressful test (forced swim test) to prevent testing carry-over effects. AnyMaze software was used to measure behavior in the open field and elevated plus mazes by recording the amount of time each mouse spent in certain parts of the maze. Future studies will examine brain changes associated with FGF2 gene deletion – particularly in astrocyte cells – which might be necessary for successful antidepressant action. Hopefully, this will elucidate novel therapeutic targets for antidepressant and anti-anxiety medication. 


Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2197 ◽  
Author(s):  
Alyssa Moore ◽  
Joshua Beidler ◽  
Mee Hong

Depression is currently treated by pharmacotherapies that can elicit debilitating side effects for patients. Novel treatment options with limited side effects are currently being researched. Resveratrol is a polyphenol and phytoalexin found in the skins of grapes, red wine, Japanese knotweed, and peanuts. It has been studied extensively for its antioxidant and anti-inflammatory properties. Resveratrol has also gained attention for its neuroprotective properties. The aim of the review was to examine the mechanisms by which resveratrol reduces depressive behaviors in animal models. In total, 22 studies met the established criteria for final review. Behavioral aspects of depression were investigated using validated measures such as the forced swimming test, tail suspension test, sucrose preference test, and open field test. While many physical measures were taken, three main biological mechanisms were explored: Regulation of the hypothalamic–pituitary–adrenal axis; decreased inflammation; and increased Brain-Derived Neurotrophic Factor and neurogenesis. Based on these findings, resveratrol may be deemed an effective treatment for depression in animal models at doses between 10–80 mg/kg/day, although higher doses had the most significant effects. Future studies should examine the effects of resveratrol on depression in humans to determine the eligibility of resveratrol as a natural antidepressant with less severe side effects.


Author(s):  
DINESH DHINGRA ◽  
SUDHA

Objectives: The present study was undertaken to investigate the antidepressant potential of trans-anethole in unstressed and stressed male mice. Methods: Swiss albino male mice were exposed to chronic unpredictable mild stress for 21 successive days. Simultaneously, trans-anethole (12.5 mg/kg, 25 mg/kg, and 50 mg/kg) and fluoxetine (20 mg/kg) per se were administered for 21 successive days to separate groups of unstressed and stressed mice. The effect of drugs on depressive-like behavior of mice was tested by tail suspension test (TST) and sucrose preference test. Results: Trans-anethole (25 mg/kg) and fluoxetine significantly decreased the immobility period of unstressed and stressed mice in TST as compared to their respective control. These drugs significantly restored the reduced sucrose preference (%) in stressed mice. Trans-anethole did not show any significant effect on locomotor activity of mice. Antidepressant-like activity of trans-anethole (25 mg/kg) was found to be comparable to fluoxetine. Trans-anethole and fluoxetine significantly inhibited brain monoamine oxidase-A (MAO-A) activity, decreased plasma nitrite, brain malondialdehyde, and increased brain reduced glutathione levels and catalase activity in unstressed and stressed mice. The drugs significantly reversed stress-induced increase in plasma corticosterone levels. Conclusion: Trans-anethole produced significant antidepressant-like activity in unstressed and stressed mice, possibly through inhibition of brain MAO-A activity and alleviation of oxidative stress. Reversal of stress-induced increase in plasma corticosterone levels might also be responsible for antidepressant-like activity of trans-anethole in stressed mice.


2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 59-60
Author(s):  
J Hanuschak ◽  
M P Louis-Auguste ◽  
G De Palma ◽  
E Verdu ◽  
R Anglin ◽  
...  

Abstract Background Major depressive disorder (MDD) affects approximately 4.4% of the global population. Despite its high prevalence, little is known about the mechanisms underlying this disorder. Recent studies in both humans and rodents have suggested that the intestinal microbiota may play a role in depression. Altered microbiota composition has been found in a subset of MDD patients. Preclinical studies have suggested that fecal microbiota transplant using pooled MDD patient samples can induce depressive-like behaviour in rodents. We have previously shown that the use of different microbiota donors with irritable bowel syndrome results in the induction of different phenotypes in recipient mice. Thus, we have hypothesized that pooling microbiota samples abrogates features that are unique to individual donors. Aims (1) Investigate whether the transfer of individual MDD patient microbiota can induce depressive-like behaviour in germ-free (GF) mice (2) Identify features of individual MDD patient microbiota that are associated with the depressive-like phenotype Methods GF NIH Swiss mice of both sexes (min. n=10 per group, total n=110) were colonized with either fecal microbiota from a single donor, MDD patient (MDD1-4) or matched healthy control (HC1-4), or pooled fecal microbiota from MDD1-4 or HC1-4. Mouse behaviour was assessed, using the open field test, three chamber sociability assay, tail suspension test, and sucrose preference test. Stool samples were collected throughout the experiment for 16S rRNA gene sequencing. Results Mice colonized with microbiota from patient MDD1 exhibited depressive-like behaviour, as assessed by the sucrose preference test and sociability assay, when compared to mice colonized with HC1 microbiota. This was not true for mice colonized with individual microbiota from the other three patients (MDD2-4) or with pooled MDD microbiota. Comparative analysis of the 16S data revealed a significant difference in Faith’s Phylogenetic Diversity between MDD1 microbiota and pooled MDD microbiota. Four bacterial species were found to be significantly associated with the depressive-like phenotype in mice: Bacteroides acidifaciens, Bacteroides ovatus, unclassified species of Phascolarctobacterium (Veillonellacae family), and Eggerthella lenta. The relative abundances of these species did not differ significantly between the two pooled groups. Conclusions Microbiota from some, but not all, MDD patients can induce a depressive-like phenotype in GF mice. The ability to induce depressive-like behaviour in GF mice is lost when microbiota from multiple patients is pooled. Specific bacterial species may be responsible for the successful transfer of the depressive-like phenotype to mice. Funding Agencies NIH


2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Jian Yang ◽  
Yu Pei ◽  
Yan-Li Pan ◽  
Jun Jia ◽  
Chen Shi ◽  
...  

Currently, antidepressants are the dominative treatment for depression, but they have limitations in efficacy and may even produce troublesome side effects. Electroacupuncture (EA) has been reported to have therapeutic benefits in the treatment of depressive disorders. The present study was conducted to determine whether EA could enhance the antidepressant efficacy of a low dose of citalopram (an SSRI antidepressant) in the chronic unpredictable stress-induced depression model rats. Here, we show that a combined treatment with 2 Hz EA and 5 mg/kg citalopram for three weeks induces a significant improvement in depressive-like symptoms as detected by sucrose preference test, open field test, and forced swimming test, whereas these effects were not observed with either of the treatments alone. Further investigations revealed that 2 Hz EA plus 5 mg/kg citalopram produced a remarkably increased expression of BDNF and its receptor TrkB in the hippocampus compared with those measured in the vehicle group. Our findings suggest that EA combined with a low dose of citalopram could produce greater therapeutic effects, thereby, predictive of a reduction in drug side effects.


Author(s):  
Jing Xia ◽  
Li Gu ◽  
Yitong Guo ◽  
Hongyan Feng ◽  
Shuhan Chen ◽  
...  

Capsaicin (CAP) is an active ingredient in chili pepper that is frequently consumed. It exerts various pharmacological activities, and also has potential effects on mental illness. However, its mechanism of antidepressant effects is still unclear. Based on the emerging perspective of the gut-brain axis, we investigated the effects of dietary CAP on gut microbes in mice with depression-like behaviors induced by lipopolysaccharide (LPS). C57BL/6J male mice (four weeks old) were given specific feed (standard laboratory chow or laboratory chow plus 0.005% CAP) for 4 months. During the last five days, LPS (0.052/0.104/0.208/0.415/0.83 mg/kg, 5-day) was injected intraperitoneally to induce depression. Behavioral indicators and serum parameters were measured, and gut microbiota were identified by sequencing analysis of the 16S gene. This study showed that dietary CAP improved depressive-like behavior (sucrose preference test, forced swimming test, tail suspension test) and levels of 5-HT and TNF-α in serum of LPS-induced mice with depression-like behaviors. In addition, CAP could recover abnormal changes in depression-related microbiota. Especially at the genus level, CAP enhanced the variations in relative abundance of certain pivotal microorganisms like Ruminococcus, Prevotella, Allobaculum, Sutterella, and Oscillospira. Correlation analysis revealed changes in microbiota composition that was closely related to depressive behavior, 5-HT and TNF-α levels. These results suggested that dietary CAP can regulate the structure and number of gut microbiota and play a major role in the prevention of depression.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yanzhen Li ◽  
Hong Zhang ◽  
Jingwen Yang ◽  
Muouyang Zhan ◽  
Xuefei Hu ◽  
...  

Abstract Background The P2Y12 receptor is a kind of purinoceptor that is engaged in platelet aggregation, and P2Y12 inhibitors have been used in clinical antithrombotic therapy. The P2Y12 receptor in microglia induces interleukin-1β (IL-1β) expression, which is a key mediator of depression in the brain. Although peripheral P2Y12 is involved in neuropathic pain, whether P2Y12 expression in the medial prefrontal cortex (mPFC) is associated with comorbidities of visceral pain and depression remains unclear. Accumulating evidence suggests that electroacupuncture (EA) is effective in treating inflammatory bowel disease (IBD), but its mechanism is unknown. This study aimed to determine whether P2Y12 expression in the mPFC is associated with comorbidities of visceral pain and depression in IBD and whether EA treats IBD by targeting the P2Y12 receptor. Methods We used 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced IBD mice. P2Y12 short hairpin RNA (shRNA) was stereotaxically injected into the bilateral mPFC. EA was performed on bilateral “Dachangshu” (BL25) acupoints once a day for 7 days. Von Frey filaments and colorectal distension were used to detect the mechanical pain threshold and visceral pain sensitivity. The sucrose preference test, tail suspension test and forced swimming test were used to evaluate depression in mice. Western blotting was used to test the expression of P2Y12 and IL-1β. Immunofluorescence staining was used to assess microglial activity. Results We found that IBD mice presented visceral pain and depression associated with increased P2Y12 expression in the mPFC. P2Y12 shRNA significantly attenuated visceral pain and depression in IBD mice. P2Y12 shRNA significantly downregulated IL-1β expression and inhibited the activation of microglia in the mPFC of IBD mice. Meanwhile, EA played a similar role of P2Y12 shRNA. EA significantly downregulated P2Y12 expression, weakened the activation of microglia, and then inhibited IL-1β expression in the mPFC, thus relieving visceral pain and depression in IBD mice. Conclusion The present study provided new ideas that the P2Y12 receptor in the mPFC could be a new target for the treatment of comorbid visceral pain and depression by EA. This may not only deepen our understanding of the analgesic and antidepressant mechanisms of EA but also promote the application of EA to treat IBD.


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