Spilanthes acmella Murr. ameliorates chronic stress through improving mitochondrial function in chronic restraint stress rats

Abstract Background To investigate the effects of chronic restraint stress on cognition and the probable molecular mechanism in mice. Methods In the current work, a restraining tube was used as a way to induce chronic stress in mice. The protein levels were determined with ELISA and western blot. A series of behavior tests, including the Morris water maze, elevated plus maze, open field test, and novel object recognition test, were also performed to examine the anxiety and the ability of learning and memory. Moreover, murine neuroblastoma N2a cells were used to confirm the findings from mice under chronic stress. Results Decreased synaptic functions were impaired in chronic stress with the downregulation of PSD95, GluR-1, the neurotrophic factor BDNF, and immediate-onset genes Arc and Egr. Chronic restraint decreased the histone acetylation level in hippocampal neurons while HDAC2 was increased and was co-localized with glucocorticoid receptors. Moreover, chronic stress inhibited the PI3K/AKT signaling pathway and induced energy metabolism dysfunctions. Conclusion This work examining the elevated levels of HDAC2 in the hippocampus may provide new insights and targets for drug development for treating many neurodegenerative diseases.

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LIMK1/2 in the mPFC Plays a Role in Chronic Stress-Induced Depressive-Like Effects in Mice

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyaa067 ◽

2020 ◽

Vol 23 (12) ◽

pp. 821-836

Author(s):

Ting-Ting Gao ◽

Yuan Wang ◽

Ling Liu ◽

Jin-Liang Wang ◽

Ying-Jie Wang ◽

...

Keyword(s):

Chronic Stress ◽

Restraint Stress ◽

Social Defeat ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Chronic Restraint Stress ◽

Lim Domain ◽

Social Defeat Stress ◽

Chronic Social Defeat Stress ◽

Pharmacological Target

Abstract Background Depression is one of the most common forms of mental illness and also a leading cause of disability worldwide. Developing novel antidepressant targets beyond the monoaminergic systems is now popular and necessary. LIM kinases, including LIM domain kinase 1 and 2 (LIMK1/2), play a key role in actin and microtubule dynamics through phosphorylating cofilin. Since depression is associated with atrophy of neurons and reduced connectivity, here we speculate that LIMK1/2 may play a role in the pathogenesis of depression. Methods In this study, the chronic unpredictable mild stress (CUMS), chronic restraint stress (CRS), and chronic social defeat stress (CSDS) models of depression, various behavioral tests, stereotactic injection, western blotting, and immunofluorescence methods were adopted. Results CUMS, CRS, and CSDS all significantly enhanced the phosphorylation levels of LIMK1 and LIMK2 in the medial prefrontal cortex (mPFC) but not the hippocampus of mice. Administration of fluoxetine, the most commonly used selective serotonin reuptake inhibitor in clinical practice, fully reversed the effects of CUMS, CRS, and CSDS on LIMK1 and LIMK2 in the mPFC. Moreover, pharmacological inhibition of LIMK1 and LIMK2 in the mPFC by LIMKi 3 infusions notably prevented the pro-depressant effects of CUMS, CRS, and CSDS in mice. Conclusions In summary, these results suggest that LIMK1/2 in the mPFC has a role in chronic stress-induced depressive-like effects in mice and could be a novel pharmacological target for developing antidepressants.

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Chronic restraint stress triggers dopaminergic and noradrenergic neurodegeneration: Possible role of chronic stress in the onset of Parkinson’s disease

Brain Behavior and Immunity ◽

10.1016/j.bbi.2015.08.015 ◽

2016 ◽

Vol 51 ◽

pp. 39-46 ◽

Cited By ~ 40

Author(s):

Shuei Sugama ◽

Kazunari Sekiyama ◽

Tohru Kodama ◽

Yoshiki Takamatsu ◽

Takato Takenouchi ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Chronic Stress ◽

Restraint Stress ◽

Chronic Restraint Stress

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Jie-Yu-He-Huan Capsule Ameliorates Anxiety-Like Behaviours in Rats Exposed to Chronic Restraint Stress via the cAMP/PKA/CREB/BDNF Signalling Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/1703981 ◽

2021 ◽

Vol 2021 ◽

pp. 1-19

Author(s):

Xiwen Geng ◽

Hongyun Wu ◽

Zifa Li ◽

Chuanfen Li ◽

Dan Chen ◽

...

Keyword(s):

Chronic Stress ◽

Hpa Axis ◽

Restraint Stress ◽

Critical Factor ◽

Receptor Expression ◽

Monoamine Oxidase A ◽

Chronic Restraint Stress ◽

Elevated Plus Maze Test ◽

Anxiolytic Drugs ◽

Bdnf Pathway

Chronic stress is a critical factor in the aetiology of anxiety disorders; however, in the clinic, enduring and preventive measures are not available, and therapeutic drugs are associated with inevitable side effects. Our study established an anxiety rat model using chronic restraint stress (CRS) and assessed these animals using the open-field test, elevated plus-maze test, and light-dark box test. Jie-Yu-He-Huan capsule (JYHH), a Chinese medicine formula, was used as a preventative drug. The HPA axis-mediated release of corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone from the hypothalamus was tested. In the hippocampus and prefrontal cortex, concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid, as well as monoamine oxidase A, glucocorticoid receptor, and 5-HT1A receptor expression levels, were measured. Furthermore, we examined protein and mRNA expression of cAMP-PKA-CREB-BDNF pathway components. The results showed that JYHH had a significant preventative effect on the anxiety-like behaviour induced by CRS and prevented abnormal changes in the HPA axis and 5-HT system. Furthermore, CRS inhibited the cAMP-PKA-CREB-BDNF pathway, which returned to normal levels following JYHH treatment. This might be the underlying molecular mechanism of the antianxiety effect of JYHH, which could provide a new clinical target for preventative anxiolytic drugs for chronic stress.

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Comparative effects of Alpha Tocopherol and Ascorbic Acid on Chronic Stress Induced Neuropeptide Y Derangements

Journal of Islamabad Medical & Dental College ◽

10.35787/jimdc.v9i1.332 ◽

2020 ◽

Vol 9 (1) ◽

pp. 33-39

Author(s):

Saadia Zainab ◽

Tahir Ahmad Munir ◽

Anjum Ilahi ◽

Adnan Saleem Khan

Keyword(s):

Ascorbic Acid ◽

Body Weight ◽

Neuropeptide Y ◽

Chronic Stress ◽

Restraint Stress ◽

Group Iv ◽

Alpha Tocopherol ◽

Chronic Restraint Stress ◽

Group Iii ◽

Group I

Background: Chronic stress decreases resilience of the body mainly due to hormonal imbalance. Neuropeptide Y-ergic system is abnormally regulated in chronic stress due to reduction-oxidation imbalance. The antioxidants such as alpha-tocopherol and ascorbic acid reduce this imbalance with positive effect on neuropeptide Y synthesis and release. This study was aimed to compare the protective effects of alpha-tocopherol and ascorbic acid on plasma neuropeptide Y levels in chronic stress.Material and Methods: This quasi-experimental study was done at Al-Nafees Medical College in collaboration with National Institute of Health Islamabad from January 2015 to January 2016 after taking institutional approval. Sixty male Sprague Dawley rats were obtained and divided equally into four groups; group I (control), group II (restraint stress group - chronic restraint stress six hours daily for 28 days), group III (restraint stress + alpha-tocopherol 50mg/kg body weight /day), and group IV (restraint stress + ascorbic acid 100mg /kg body weight /day). Cardiac puncture was done to obtain blood for biochemical analysis.Results: A significant decrease in plasma neuropeptide Y levels was seen in group II compared to group I, group III and group IV. However, alpha-tocopherol administration in group III showed positive effects on maintenance of plasma neuropeptide Y concentration with better p trend than that of ascorbic acid supplementation in group IV.Conclusions: Alpha-tocopherol supplementation has more potent effect than that of ascorbic acid on chronic restraint stress induced derangements in neuropeptide Y levels. It leads to less imbalance in neuropeptide Y levels during chronic stress.Key words: Ascorbic Acid, Alpha-Tocopherol, Chronic Stress, Neuropeptide Y

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Chronic maternal stress inhibits the capacity to up-regulate placental 11β-hydroxysteroid dehydrogenase type 2 activity

Journal of Endocrinology ◽

10.1677/joe.1.06374 ◽

2005 ◽

Vol 186 (3) ◽

pp. R7-R12 ◽

Cited By ~ 145

Author(s):

Leonie A M Welberg ◽

K V Thrivikraman ◽

Paul M Plotsky

Keyword(s):

Chronic Stress ◽

Restraint Stress ◽

Hydroxysteroid Dehydrogenase ◽

Acute Exposure ◽

Placental Barrier ◽

Chronic Restraint Stress ◽

The Third ◽

The Face ◽

Acute Stressor

This study investigated the effects of acute and chronic restraint stress during the third week of pregnancy on placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity in rats. Acute exposure to stress on gestational day 20 immediately up-regulated placental 11β-HSD2 activity by 160%, while chronic stress from day 14 to day 19 of pregnancy did not significantly alter basal 11β-HSD2 activity. However, the latter reduced the capacity to up-regulate placental 11β-HSD2 activity in the face of an acute stressor by 90%. Thus, immediate up-regulation of 11β-HSD2, the feto-placental barrier to maternal corticosteroids, may protect the fetus against stress-induced high levels of maternal corticosteroids, but exposure to chronic stress greatly diminishes this protection.

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Protective Effects of Crocetin on Depression-like Behavior Induced by Immobilization in Rat

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527317666180515120212 ◽

2018 ◽

Vol 17 (5) ◽

pp. 361-369 ◽

Cited By ~ 5

Author(s):

Tahereh Farkhondeh ◽

Saeed Samarghandian ◽

Fariborz Samini ◽

Ali Rajabpour Sanati

Keyword(s):

Antioxidant Enzymes ◽

Oxidative Damage ◽

Chronic Stress ◽

Neurodegenerative Disorders ◽

Restraint Stress ◽

Protective Effects ◽

Chronic Restraint Stress ◽

Stress Group ◽

Immobility Time ◽

The Brain

Background & Objective: Crocetin, an active ingredient of saffron, has been recognized as a potent antioxidant. Plant extracts or their components may be useful in ameliorating the various diseases, including neurodegenerative disorders. This study investigated the effects of crocetin on oxidative damage induced by chronic restraint stress in the rat brain. For this reason, rats were kept in the restrainers for 1 hour every day, for 21 consecutive days. The animals were injected crocetin (20, 40, 60 mg/kg) or vehicle daily for 21 days. Findings showed that the immobility time significantly increased in the rodents subjected to the chronic stress compared with the normal group. However, the number of crossing beams in the rats submitted to the chronic stress significantly decreased versus the non-stress rats. Treatment with crocetin ameliorated the immobility time and the number of crossing in the chronic restraint stress rats versus the non-treated stress group. Crocetin also reverted the levels of MDA and GSH and also the activities of antioxidant enzymes to the normal levels in the stress groups. Conclusion: The present study suggests that crocetin may be useful for the management of depressantlike effects induced by chronic stress through decreasing oxidative damage in the brain.

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Oxytocin involves in chronic stress-evoked melanoma metastasis via β-arrestin 2 mediated-pathways

10.1101/494484 ◽

2018 ◽

Author(s):

Haoyi Ji ◽

Na Liu ◽

Jing Li ◽

Dawei Chen ◽

Dan Luo ◽

...

Keyword(s):

Chronic Stress ◽

Lung Metastasis ◽

Restraint Stress ◽

Underlying Mechanism ◽

Melanoma Metastasis ◽

Chronic Restraint Stress ◽

Oxytocin Receptors ◽

Increased Risk

Stress is associated with an increased risk of lung metastasis in melanoma. However, the underlying mechanism is elusive. Oxytocin (OXT), a neurohormone produced by the hypothalamus, plays a vital role in laboring induction and lactation. Emerging evidence suggests that OXT also regulates human emotions, social cognition, social behaviors and stress-related disorders. Here, we reported that a significant up-regulation of oxytocin receptors (OXTRs) was observed in malignant melanoma. The activation of oxytocin receptors (OXTRs) dramatically promoted migration, invasion and angiogenesis but not the proliferation of melanoma cells in vitro and in vivo via β-arrestin 2-dependent ERK-VEGF/ MMP-2 pathway. Next, chronic restraint stress significantly elevated the plasma level of OXT. Notably, 21 days chronic restraint stress facilitated lung metastasis of melanoma and reduced overall survival in mice, which were largely abrogated by knocking down either OXTR or β-arrestin 2. These findings provide evidence that chronic stress hormone-OXT promotes lung metastasis of melanoma via a β-arrestin 2-dependent mechanism and suggest that OXT, a novel pro-metastasis factor, is a potential therapeutic target for melanoma.

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Lithium modulates the chronic stress-induced effect on blood glucose level of male rats

Archives of Biological Sciences ◽

10.2298/abs1002289p ◽

2010 ◽

Vol 62 (2) ◽

pp. 289-295 ◽

Cited By ~ 3

Author(s):

Natasa Popovic ◽

Snezana Pajovic

Keyword(s):

Blood Glucose ◽

Blood Glucose Level ◽

Chronic Stress ◽

Glucose Level ◽

Restraint Stress ◽

Elevated Serum ◽

Corticosterone Level ◽

Male Rats ◽

Chronic Restraint Stress ◽

Serum Corticosterone

In the present study we examined gross changes in the mass of whole adrenal glands and that of the adrenal cortex, as well as the serum corticosterone and glucose level of mature male Wistar rats subjected to three different treatments: animals subjected to chronic restraint-stress, animals injected with lithium (Li) and chronically stressed rats treated with Li. Under all three conditions we observed hypertrophy of whole adrenals, as well as the adrenal cortices. Chronic restraint stress, solely or in combination with Li treatment, significantly elevated the corticosterone level, but did not change the blood glucose level. Animals treated only with Li exhibited an elevated serum corticosterone level and blood glucose level. The aim of our study was to investigate the modulation of the chronic stress-induced effect on the blood glucose level by lithium, as a possible mechanism of avoiding the damage caused by chronic stress. Our results showed that lithium is an agent of choice which may help to reduce stress-elevated corticosterone and replenish exhausted glucose storages in an organism.

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Reduced anterior cingulate cortex volume induced by chronic stress correlates with increased behavioral emotionality and decreased synaptic puncta density

10.1101/2020.08.31.275750 ◽

2020 ◽

Author(s):

Keith A. Misquitta ◽

Amy Miles ◽

Thomas D. Prevot ◽

Jaime K. Knoch ◽

Corey Fee ◽

...

Keyword(s):

Nucleus Accumbens ◽

Anterior Cingulate Cortex ◽

Chronic Stress ◽

Restraint Stress ◽

Structural Changes ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

List Type ◽

Chronic Restraint Stress ◽

Structural Covariance

AbstractClinical and preclinical studies report that chronic stress induces behavioral deficits as well as volumetric changes and synaptic alterations in corticolimbic brain regions including the anterior cingulate cortex (ACC), amygdala (AMY), nucleus accumbens (NAc) and hippocampus (HPC). In this study, we aimed to investigate the structural changes associated with chronic restraint stress (CRS) exposure and determine the relation between these volumetric changes with behavioral and synaptic alterations. Mice exposed to 2 and 5 weeks of CRS exhibited a significant increase in behavioral emotionality. Macrostructural changes assessed via MRI identified a negative CRS effect on total brain volume, proportional to behavioral emotionality. Region-specific changes within corticolimbic brain structures identified that only the ACC showed significant decrease in volume following CRS exposure (p<0.05). Reduced ACC correlated with increased behavioral emotionality (r=−0.50; p=0.002). Although not significantly altered by CRS, AMY and NAc (but not the HPC) volumes were negatively correlated with behavioral emotionality. Structural covariance network analysis revealed progressive decreased ACC degree following CRS exposure. Finally, reduced ACC volume correlated with decreased PSD95 (but not VGLUT1) puncta density (r=0.35, p<0.05), which also correlated with increased behavioral emotionality (r=−0.36, p<0.05), together suggesting that altered synaptic strength is an underlying substrate of the volumetric and behavioral effects of CRS Our results demonstrate that chronic stress effects on ACC volume and synaptic density are linked to the expression of depressive-like deficits. Our findings highlight key structural and morphological alterations in the ACC relevant to stress-related illness including mood and anxiety disorders.HighlightsChronic restraint stress induces decreases in anterior cingulate volume at 2 and 5 weeks following stress exposureVolume of the anterior cingulate cortex, amygdala and nucleus accumbens negatively correlate with behavioral emotionalityChronic stress induces a progressive decrease in strength and degree in structural covariance network connectivity of the anterior cingulate cortexPuncta density in the anterior cingulate cortex of post-synaptic marker PSD95 negatively correlates with behavioral emotionality and positively correlates with anterior cingulate cortex volume.

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