N-acetylcysteine attenuates neuroinflammation associated depressive behavior induced by chronic unpredictable mild stress in rat

Fernandes, Joneth; Gupta, Girdhari Lal

doi:10.1016/j.bbr.2019.02.025

Cited by 56 publications

(40 citation statements)

References 70 publications

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“…NAC has been used as an adjuvant therapy in many psychiatric disorders (e.g., Alzheimer´s disease, schizophrenia, autism, addiction, substance abuse, obsessive-compulsive and mood disorders [24,[99][100][101][102][103][104]), with promising results and no relevant side effects after its administration against inflammation [97]. The use of NAC in a chronic unpredictable mild-stress animal model inhibited the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in the hippocampus and prefrontal cortex and exhibited antidepressant-like effects [71]. However, in a recent study, NAC treatment did not show any effect on the serum levels of IL-6, IL-8, TNF-α, IL-10, or C-reactive protein in a clinical trial for bipolar depression, possibly due to the small sample size used in this study [72].…”

Section: N-acetylcysteine Decreases Inflammatory Responsementioning

confidence: 99%

Antioxidants as a Potential Target against Inflammation and Oxidative Stress in Attention-Deficit/Hyperactivity Disorder

et al. 2020

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Psychostimulants and non-psychostimulants are the medications prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD). However, several adverse results have been linked with an increased risk of substance use and side effects. The pathophysiology of ADHD is not completely known, although it has been associated with an increase in inflammation and oxidative stress. This review presents an overview of findings following antioxidant treatment for ADHD and describes the potential amelioration of inflammation and oxidative stress using antioxidants that might have a future as multi-target adjuvant therapy in ADHD. The use of antioxidants against inflammation and oxidative conditions is an emerging field in the management of several neurodegenerative and neuropsychiatric disorders. Thus, antioxidants could be promising as an adjuvant ADHD therapy.

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Section: N-acetylcysteine Decreases Inflammatory Responsementioning

confidence: 99%

Antioxidants as a Potential Target against Inflammation and Oxidative Stress in Attention-Deficit/Hyperactivity Disorder

et al. 2020

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“…Recent evidence has indicated that depression is associated with increases in oxidative stress and inflammation, followed by a consequent activation in neuronal apoptosis. Such responses are, in part, due to environmental risk factors which then produce a neuroprogression of events resulting in the development of depression-like behaviors [4][5][6]. Results from clinical reports have shown that inflammation is closely associated with the pathogenesis of depression, as indicated by elevated levels of proinflammatory cytokines found in the peripheral circulation and some brain regions of depressed patients [7,8].…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside-Rg1 Rescues Stress-Induced Depression-Like Behaviors via Suppression of Oxidative Stress and Neural Inflammation in Rats

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Depression is an inflammatory-related condition, with the progression in neuronal damage resulting in major depression disorder. Ginsenoside-Rg1, a sterol extract from the herb Panax ginseng, has been shown to exert neuroprotective effects upon neurodegeneration disorders. However, whether ginsenoside-Rg1 confers antidepressant-like effects on neuroinflammation as associated with depression, as well as the possible mechanism involved in these neuroprotective effects, is currently unclear. In the present report, we show that treatment with ginsenoside-Rg1 (40 mg/kg, i.p.) significantly ameliorated depressive-like behaviors as induced by chronic unpredictable mild stress (CUMS) in a rat model of depression. Moreover, these CUMS rats treated with ginsenoside-Rg1 showed reductions in the levels of the oxidative stress products and the activity in the antioxidant stress kinase. Furthermore, CUMS rats treated with ginsenoside-Rg1 showed ameliorated neuroinflammation and associated neuronal apoptosis along with a reduction in dendritic spine atrophy and display of depressive behaviors. Taken together, the results of this study suggest that ginsenoside-Rg1 produces antidepressant-like effects in CUMS-exposed rats; and one of the mechanisms for these antidepressant-like effects of ginsenoside-Rg1 appears to involve protection against oxidative stress and thus the neuronal deterioration resulting from inflammatory responses. These findings provide evidence for the therapeutic potential of ginsenoside-Rg1 in the treatment of stress-related depression.

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“…OFT is often used to quantitatively and qualitatively measure the general locomotor activities and willingness of rodents to explore their novel environments 49 . Therefore, OFT and actophotometers used in developing animal models assesses rodent's exploratory and locomotor behaviors 35 . In the present study, rats exposed to 8 weeks of CUMS had reduced locomotor activities, as demonstrated by a significant reduction of number of lines crossings in the OFT suggesting anxiety-like effect.…”

Section: Discussionmentioning

confidence: 99%

“…oral administration) and CA (200, 400 and 800 mg/kg) p.o. were on the basis of previous studies 24,35 . Fluoxetine and CA were administered orally because it was considered the best route of drug administration for psychiatric patients 35 .…”

Section: Drugs and Chemicalsmentioning

confidence: 99%

Centella asiatica prevents chronic unpredictable mild stress-induced behavioral changes in rats

et al. 2019

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Background: Depression is a psychological disorder which is associated with mood swings and cognitive deficits, and is ranked third among the leading causes of global health care burden. Chronic unpredictable mild stress (CUMS) has been shown to induce depression-like behaviors in rodents, which exhibit similarities to the human form of depression. Centella asiatica (CA) is an ancient medicinal plant which has neuroprotective potential. This work aimed to assess the protective role of CA on CUMS-induced rats. Methods: Thirty six rats randomly divided into six groups were used for the evaluation. The groups were as follows: 1, Unstressed + normal saline (control); 2, CUMS + normal saline (model); 3, CUMS + fluoxetine (10 mg/kg) standard antidepressant; 4-6, CUMS + CA (200, 400 & 800 mg/kg). Nine different stressors (S) (S1: 24-h food deprivation, S2: 24- h water deprivation, S3: 5-min cold swimming (at 5◦C), S4: 12-h change of cage mate, S5: 1-min tail pinch (1 cm from the tip of the tail), S6: 12-h cage tilt (at 45◦), S7: 12-h overcrowding of cage, S8: 12-h wet bedding with 200 mL of water, and S9: 4-h physical restraint) were administered to the stressed groups with at least 2 stressors per day. The treatments lasted for 8 weeks, and the rats were evaluated through open field test (OFT) and elevated plus maze (EPM) for anxiety-like behavior, forced swimming test (FST) for depression-like behaviour, and T-maze spontaneous alternation for learning and memory. Furthermore, serum cortisol levels were also evaluated. Results: CUMS-induced rats showed anxiety-like behaviors in OFT and EPM tests, depression-like behavior in FST and cognitive deficits in T-maze test, as well as increased serum cortisol levels. Conversely, administration of CA (at 400 and 800 mg/kg doses) and fluoxetine (at 10 mg/kg dose) prevented the aberrant behavioral changes and also the changes in the serum cortisol levels. No significant differences of behaviors were observed between the groups of rats administered with CA (400 and 800 mg/kg) and those administered with fluoxetine (10 mg/kg), suggesting that the therapeutic potential of CA is comparable to that of fluoxetine. Conclusion: The data obtained showed that CA, at doses of 400 and 800 mg/kg, effectively reversed the anxiety and depression-like behaviors, amnesic behaviors, as well as serum cortisol levels in a CUMS-induced rat model of depression. This suggests that CA is a potential candidate for the development of future anti-depressants.

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N-acetylcysteine attenuates neuroinflammation associated depressive behavior induced by chronic unpredictable mild stress in rat

Cited by 56 publications

References 70 publications

Antioxidants as a Potential Target against Inflammation and Oxidative Stress in Attention-Deficit/Hyperactivity Disorder

Antioxidants as a Potential Target against Inflammation and Oxidative Stress in Attention-Deficit/Hyperactivity Disorder

Ginsenoside-Rg1 Rescues Stress-Induced Depression-Like Behaviors via Suppression of Oxidative Stress and Neural Inflammation in Rats

Centella asiatica prevents chronic unpredictable mild stress-induced behavioral changes in rats

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