Therapeutic potential of glutathione-enhancers in stress-related psychopathologies

Zalachoras, Ioannis; Hollis, Fiona; Ramos-Fernández, Eva; Trovò, Laura; Sonnay, Sarah; Geiser, Eveline; Preitner, Nicolas; Steiner, Pascal; Sandi, Carmen; Morató, Laia

doi:10.1016/j.neubiorev.2020.03.015

Cited by 42 publications

(45 citation statements)

References 374 publications

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“…It is known that ROS accumulate following exposure to obesogenic diets and obesity in rodents and humans [27][28][29][30][31]. Due to its high lipid content, the brain is vulnerable to ROS damage, which can have devastating effects on brain function and in the etiology of anxiety and stress-related disorders [32][33][34][35]. Together, these findings underscore the importance of oxidative stress as a potential molecular link connecting obesity to increased stress vulnerability.…”

Section: Highlightsmentioning

confidence: 99%

Section: Highlightsmentioning

confidence: 99%

“…astrocytes use glycolysis for energy production and, as a consequence, have been associated with a higher generation of mitochondrial reactive oxygen species (ROS) [26].It is known that ROS accumulate following exposure to obesogenic diets and obesity in rodents and humans [27][28][29][30][31]. Due to its high lipid content, the brain is vulnerable to ROS damage, which can have devastating effects on brain function and in the etiology of anxiety and stress-related disorders [32][33][34][35]. Together, these findings underscore the importance of oxidative stress as a potential molecular link connecting obesity to increased stress vulnerability.The functional coupling between astrocytes and neurons contributes to redox metabolism, which is tightly regulated by antioxidant systems [26].…”

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confidence: 99%

“…GSR's role relies on regenerating the reduced glutathione product of the GPx following GPx activities on lipid and non-lipid hydro-peroxides [40]. Studies demonstrate that lack of activity on this system leads to ROS buildup, inflammation, and may represent an important predisposing factor for anxiety and stress-related neuropsychiatric disorders [32][33][34][35].Given that obesogenic diets induce oxidative stress, it is logical to hypothesize that the antioxidant network will mount a compensatory response to preserve redox homeostasis. Therefore, examining the response of the antioxidant system to obesogenic diets may provide valuable insight into the potential contribution of oxidative stress to…”

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confidence: 99%

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Oxidative Stress and Neuroinflammation in a Rat Model of Co-Morbid Obesity and Psychogenic Stress

Santana

Vega-Torres

Ontiveros-Angel

et al. 2020

Preprint

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Contributions: JMS, wrote manuscript, performed Western blot experiments and analyses; JDV, design and performed behavioral experiments, wrote manuscript; YAT, performed Western blot experiments; POA, performed and analyzed ELISA experiments, prepared illustrations, wrote manuscript; JBL, analyzed behavioral data; AYCG and EAB, performed Western blots; DZO and CAC, peformed Western blot analyses; JDF, planned experiments, analyzed data, wrote manuscript. AbstractBackground: There is growing recognition for a reciprocal, bidirectional link between anxiety disorders and obesity. Although the mechanisms linking obesity and anxiety remain speculative, this bidirectionality suggests shared pathophysiological processes. Neuroinflammation and oxidative damage are implicated in both pathological anxiety and obesity. This study investigates the relative contribution of comorbid dietinduced obesity and stress-induced anxiety to neuroinflammation and oxidative stress.Methods: Thirty-six (36) male Lewis rats were divided into four groups based on diet type and stress exposure: 1) control diet unexposed (CDU) and 2) exposed (CDE), 3)Western-like high-saturated fat diet unexposed (WDU) and 4) exposed (WDE).Neurobehavioral tests were performed to assess anxiety-like behaviors. The catalytic concentrations of glutathione peroxidase and reductase were measured from plasma samples, and neuroinflammatory/oxidative stress biomarkers were measured from brain samples using Western blot. Correlations between behavioral phenotypes and biomarkers were assessed with Pearson's correlation procedures. Results:We found that WDE rats exhibited markedly increased levels of glial fibrillary acidic protein (185%), catalase protein (215%), and glutathione reductase (GSR) enzymatic activity (418%) relative to CDU rats. Interestingly, the brain protein levels of glutathione peroxidase (GPx) and catalase were positively associated with body weight and behavioral indices of anxiety. Conclusions:Together, our results support a role for neuroinflammation and oxidative stress in heightened emotional reactivity to obesogenic environments and psychogenic stress. Uncovering adaptive responses to obesogenic environments characterized by 3 high access to high-saturated fat/high-sugar diets and toxic stress has the potential to strongly impact how we treat psychiatric disorders in at-risk populations. Highlights:• Predatory odor stress heightens footshock reactivity and anxiety-like behaviors in Lewis rats.• WD intake increases glutathione reductase activity in plasma.• WD intake and PS exposure acted synergistically to increase the brain protein levels of catalase and the glial fibrillary acidic protein.• The protein levels and activities of some redox/neuroinflammatory biomarkers are closely associated with behavioral proxies related to fear and anxiety in rats. astrocytes use glycolysis for energy production and, as a consequence, have been associated with a higher generation of mitochondrial reactive oxygen species (ROS) [26].It is known that ROS accumula...

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confidence: 99%

Section: Highlightsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Oxidative Stress and Neuroinflammation in a Rat Model of Co-Morbid Obesity and Psychogenic Stress

Santana

Vega-Torres

Ontiveros-Angel

et al. 2020

Preprint

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“…The inter-dependent nature of immunity and psychological state is established and decides the outcome of disorders. An immune response can be largely affected by mental well-being, and depression can negatively affect its outcome ( Rajkumar, 2020 ; Zalachoras et al, 2020 ). Targeting either one of depression or immunity may face insufficiency; dual-acting drug hold promise to improve health amid COVID-19 pandemic.…”

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Fight COVID-19 depression with immunity booster: Curcumin for psychoneuroimmunomodulation

Soni

Mehta

Shukla

et al. 2020

Asian Journal of Psychiatry

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Plasma metabolomics reveals the intervention mechanism of different types of exercise on chronic unpredictable mild stress-induced depression rat model

Liu,

Zhang,

Tian

et al. 2023

Metab Brain Dis

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To study the effects of different types of exercise on the plasma metabolomics of chronic unpredictable mild stress (CUMS)-induced depressed rats based on 1 H-NMR metabolomics techniques, and to explore the potential mechanisms of exercise for the treatment of depression. MethodsRats were randomly divided into blank control group (C), CUMS control group (D), pre-exercise group (P), aerobic exercise group (A), resistance exercise group (R), and aerobic + resistance exercise group (AR).The corresponding protocol intervention was applied to each group of rats. Body weight, sucrose preference and open eld tests were performed weekly during the experiment to evaluate the extent of depression in rats. Plasma samples from each group of rats were collected at the end of the experiment, and then the plasma was analyzed by 1 H-NMR metabolomics combined with multivariate statistical analysis methods to identify differential metabolites and perform metabolic pathway analysis. Results(1) Compared with the group D, the body weight, sucrose preference rate, and the number of crossings and standings in the different types of exercise groups were signi cantly improved (p < 0.05 or p < 0.01).(2) Compared to group C, a total of 15 differential metabolites associated with depression were screened in the plasma of rats in group D, involving 6 metabolic pathways. Group P can regulate the levels of 6 metabolites: valine, lactate, inositol, glucose, phosphocreatine, acetoacetic acid. Group A can regulate the levels of 6 metabolites: N-acetylglycoprotein, leucine, lactate, low density lipoprotein, glucose, acetoacetic acid. Group R can regulate the levels of 6 metabolites: choline, lactate, inositol, glucose, phosphocreatine, acetoacetic acid. Group AR can regulate the levels of 5 metabolites: choline, citric acid, glucose, acetone, acetoacetic acid. ConclusionThe different types of exercise groups can improve the depressive symptoms in CUMS rats, and there are common metabolites and metabolic pathways for their mechanism of effects. This study provides a powerful analytical tool to study the mechanism of the antidepressant effect of exercise, and provides an important method and basis for the early diagnosis, prevention and treatment of depression.

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Therapeutic potential of glutathione-enhancers in stress-related psychopathologies

Cited by 42 publications

References 374 publications

Oxidative Stress and Neuroinflammation in a Rat Model of Co-Morbid Obesity and Psychogenic Stress

Oxidative Stress and Neuroinflammation in a Rat Model of Co-Morbid Obesity and Psychogenic Stress

Fight COVID-19 depression with immunity booster: Curcumin for psychoneuroimmunomodulation

Plasma metabolomics reveals the intervention mechanism of different types of exercise on chronic unpredictable mild stress-induced depression rat model

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