Mechanisms underlying remediation of depression-associated anxiety by chronic N-acetyl cysteine treatment

Chakraborty, Suwarna; Tripathi, Sunil Jamuna; Raju, T.R.; Rao, B S Shankaranarayana

doi:10.1007/s00213-020-05585-x

Cited by 15 publications

(11 citation statements)

References 71 publications

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“…The corticosterone concentration of rats in the CUMS model increased significantly ( Figure 3C ); the adrenal index also significantly increased ( Figure 3D ). These results were consistent with previous studies, indicating that the CUMS procedure successfully induced depression ( Rubin et al, 1996 ; Herzog et al, 2009 ; Chakraborty et al, 2020 ; Gu et al, 2020 ; Stoneham et al, 2021 ; Xu et al, 2022 ). At the end of 12 weeks, we investigated the serotonin level in plasma samples and observed the trend of a decreased concentration of 5-HT in the CUMS rats.…”

Section: Resultssupporting

confidence: 93%

Antidepressant Shugan Jieyu Capsule Alters Gut Microbiota and Intestinal Microbiome Function in Rats With Chronic Unpredictable Mild Stress -Induced Depression

Tan

Zhu

et al. 2022

Front. Pharmacol.

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Shugan Jieyu Capsule (SG) has been widely used in China to treat mild to moderate depression. Hypericum perforatum L. (St John’s Wort, SJW) is the main ingredient of SG and has been used as herbal medicine to treat depression in western countries. However, it is known that SJW has low bioavailability and does not easily get through the blood-brain barrier. Therefore, how SG plays an antidepressant effect in the central nervous system (CNS) remains an urgent problem to be solved. Mounting research has described the relationship between antidepressants and intestinal microbiota to illuminate antidepressive mechanisms in the CNS. We aimed to investigate the effects of therapy with SG on the function of gut microbiota and intestinal microbiota in rats with chronic unpredictable mild stress (CUMS)-induced depression. The psychophysiological state and the hypothalamic-pituitary-adrenal axis function of rats are evaluated through behavioral experiments, corticosterone levels, serotonin levels, and adrenal index measurements. 16S rDNA amplicon sequencing is used to test the changes in gut microbiota and make functional predictions of genes. With treatment of SG, the depression-like behaviors of CUMS-induced rats were reversed; the corticosterone levels and the adrenal index decreased significantly; the level of serotonin increased significantly; and the alpha and beta diversity analysis of microbiota showed an increase in the richness and uniformity of the flora were increased. SG regulated the relative abundance of Actinobacteria, Erysipelotrichaceae, Bifidobacteriaceae, Atopobiaceae, Dubosiella, and Bifidobacterium; Linear discriminant analysis effect size analysis demonstrated that Lactobacillaceae (family level), Lactobacillus (genus level), Lactobacillales (order level), Bacilli (class level), and Lactobacillus-reuteri (species level) were biomarkers in the SG group samples, and also likely to modulate metabolic pathways, such as those involved in carbohydrate metabolism, amino acid metabolism, and signal transduction. These data clearly illustrated the effect of SG on gut microbiome, thus laying the foundation for uncovering more insights on the therapeutic function of the traditional Chinese antidepressants. The potential of SG on mechanisms of antidepression to alter gut microbiota and intestinal microbiome function exposed to CUMS can be explored.

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Section: Resultssupporting

confidence: 93%

Antidepressant Shugan Jieyu Capsule Alters Gut Microbiota and Intestinal Microbiome Function in Rats With Chronic Unpredictable Mild Stress -Induced Depression

Tan

Zhu

et al. 2022

Front. Pharmacol.

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“…We cannot currently determine, if the treatment during juvenile age (∼P22–P70) would have been sufficient to cause the beneficial effects on cognitive flexibility and anhedonia, or if they were induced by the second treatment during adulthood. While this remains to be assessed in a future study, it has been established in rat models of depression that sub-chronic pre-treatment in adulthood alone is sufficient to improve sucrose preference ( Fernandes and Gupta, 2019 ; Chakraborty et al, 2020a , b ).…”

Section: Discussionmentioning

confidence: 99%

Chronic N-acetylcysteine treatment improves anhedonia and cognition in a mouse model of the schizophrenia prodrome

Bühner

Kapanaiah

Kätzel

2022

Front. Behav. Neurosci.

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Schizophrenia is a severe psychiatric disorder whose neurodevelopmental pathogenesis includes a prodromal phase before its diagnostically decisive—namely psychotic—symptoms are present. This prodrome is characterized by cognitive and affective deficits, and it may constitute a critical time period for an early therapeutic intervention to improve or even prevent further disease development. N-acetylcysteine (NAC) is an easily repurposable compound that has recently shown promise in improving non-psychotic symptoms in patients with established schizophrenia. Its therapeutic mechanism may involve the amelioration of circuit abnormalities like a hyper-glutamatergic state and oxidative stress in cortex which have been proposed to drive the pathogenesis of this disease. However, it is currently unknown to what extent NAC can actually improve prodromal aberrations. To investigate this preclinically, we deployed the cyclin-D2 knockout mouse model (CD2-KO) that shares physiological and behavioral abnormalities with the schizophrenia prodrome, including a hyperactive CA1 region, and cognitive and affective deficits. Applying NAC chronically in drinking water (0.9 g/l) during development (∼P22–P70), we found that excessive novelty-induced hyperlocomotion was neither ameliorated during (∼P68) nor after (∼P75) treatment; similarly, T-maze working memory (tested after treatment; ∼P84) was unaffected. However, once chronic NAC treatment was resumed (at approximately P134) in those mice that had received it before, working memory, cognitive flexibility (tested under NAC), and anhedonia (sucrose-preference, tested 1 day after NAC-treatment stopped) were improved in CD2-KO mice. This suggests that chronic NAC treatment may be a therapeutic strategy to improve some cognitive and affective dysfunctions in the schizophrenia prodrome.

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“…Administration of N-acetyl cysteine (NAC), an antioxidant, to mice reduced depressive-like behaviors and restored the corticosterone levels in the amygdala [227]. It also provided a neuroprotective effect against oxidative stress and DNA damage in the hippocampus due to NAC antioxidant and anti-inflammatory effects [228].…”

Section: Inflammationmentioning

confidence: 99%

Novel Pharmacological Approaches to the Treatment of Depression

Elias

Zhang

Manners

2022

Life

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Major depressive disorder is one of the most prevalent mental health disorders. Monoamine-based antidepressants were the first drugs developed to treat major depressive disorder. More recently, ketamine and other analogues were introduced as fast-acting antidepressants. Unfortunately, currently available therapeutics are inadequate; lack of efficacy, adverse effects, and risks leave patients with limited treatment options. Efforts are now focused on understanding the etiology of depression and identifying novel targets for pharmacological treatment. In this review, we discuss promising novel pharmacological targets for the treatment of major depressive disorder. Targeting receptors including N-methyl-D-aspartate receptors, peroxisome proliferator-activated receptors, G-protein-coupled receptor 39, metabotropic glutamate receptors, galanin and opioid receptors has potential antidepressant effects. Compounds targeting biological processes: inflammation, the hypothalamic-pituitary-adrenal axis, the cholesterol biosynthesis pathway, and gut microbiota have also shown therapeutic potential. Additionally, natural products including plants, herbs, and fatty acids improved depressive symptoms and behaviors. In this review, a brief history of clinically available antidepressants will be provided, with a primary focus on novel pharmaceutical approaches with promising antidepressant effects in preclinical and clinical studies.

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Mechanisms underlying remediation of depression-associated anxiety by chronic N-acetyl cysteine treatment

Cited by 15 publications

References 71 publications

Antidepressant Shugan Jieyu Capsule Alters Gut Microbiota and Intestinal Microbiome Function in Rats With Chronic Unpredictable Mild Stress -Induced Depression

Antidepressant Shugan Jieyu Capsule Alters Gut Microbiota and Intestinal Microbiome Function in Rats With Chronic Unpredictable Mild Stress -Induced Depression

Chronic N-acetylcysteine treatment improves anhedonia and cognition in a mouse model of the schizophrenia prodrome

Novel Pharmacological Approaches to the Treatment of Depression

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