scholarly journals Chronic restraint stress impairs cognition via modulating HDAC2 expression

2021 ◽  
Vol 12 (1) ◽  
pp. 154-163
Author(s):  
Jie Wu ◽  
Cui Liu ◽  
Ling Zhang ◽  
Bing He ◽  
Wei-Ping Shi ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Hippocampal Neurons ◽  
Restraint Stress ◽  
Glucocorticoid Receptors ◽  
Chronic Restraint Stress ◽  
Akt Signaling Pathway ◽  
Object Recognition Test ◽  
Protein Levels ◽  
Synaptic Functions ◽  
Plus Maze

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.

Antidepressant-Like Effects of Vaccinium bracteatum in Chronic Restraint Stress Mice: Functional Actions and Mechanism Explorations

2018 ◽  
Vol 46 (02) ◽  
pp. 357-387 ◽  
Author(s):  
Dool-Ri Oh ◽  
Yujin Kim ◽  
Eun-Jin Choi ◽  
Myung-A Jung ◽  
Kyo-Nyeo Oh ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Signaling Pathway ◽  
Restraint Stress ◽  
Forced Swim Test ◽  
Akt Signaling ◽  
Antagonistic Effect ◽  
Chronic Restraint Stress ◽  
Akt Signaling Pathway ◽  
Neuroprotective Effects ◽  
Immobility Time

The fruit of Vaccinium bracteatum Thunb. (VBF) is commonly known as the oriental blueberry in Korea. The aim of this study was to evaluate the antidepressant-like effects of water VBF extract (VBFW) in a mouse model of chronic restraint stress (CRS) and to identify the underlying mechanisms of its action. The behavioral effects of VBFW were assessed in the forced swim test (FST) and open field test (OFT). The levels of serum corticosterone (CORT), brain monoamines, in addition to the extracellular signal-regulated kinases (ERKs)/protein kinase B (Akt) signaling pathway were evaluated. VBFW treatment significantly reduced the immobility time and increased swimming time in FST without altering the locomotor activity in unstressed mice. Furthermore, CRS mice treated with VBFW exhibited a significantly decreased immobility time in FST and serum CORT, increased locomotor activity in OFT, and enhanced brain monoamine neurotransmitters. Similarly, VBFW significantly upregulated the ERKs/Akt signaling pathway in the hippocampus and PFC. In addition, VBFW may reverse CORT-induced cell death by enhancing cyclic AMP-responsive element-binding protein expression through the up-regulation of ERKs/Akt signaling pathways. In addition, VBFW showed the strong antagonistic effect of the 5-HT[Formula: see text] receptor by inhibiting 5-HT-induced intracellular Ca[Formula: see text] and ERK1/2 phosphorylation. Our study provides evidence that antidepressant-like effects of VBFW might be mediated by the regulation of monoaminergic systems and glucocorticoids, which is possibly associated with neuroprotective effects and antagonism of 5-HT[Formula: see text] receptor.

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

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.

scholarly journals Therapeutic STING activation boosts microglia phagocytosis and ameliorates depression-like behaviors during chronic restraint stress

2021 ◽  
Author(s):  
Qian Zhai ◽  
Yanpeng Zhang ◽  
Shuwen Tan ◽  
Jianyu Sun ◽  
Mao Ye ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Restraint Stress ◽  
Potential Role ◽  
Therapeutic Potential ◽  
Chronic Restraint Stress ◽  
Expression Levels ◽  
Cell Counts ◽  
Latex Beads ◽  
Plus Maze

Abstract Background The STING-TBK1-IRF3 signaling pathway involves in modulating host innate immunity, however, the potential role of STING signaling pathway in chronic restraint stress model has not been determined. The aim of this study is to explore the underlying role of STING signaling pathway in regulating neuroinflammation, as well as to evaluate the therapeutic potential of STING agonist during chronic restraint stress. Methods C57BL/6 mice were subject to 14-day intermittent restraint stress. Sucrose preference, elevated plus maze and tail suspension tests were measured in chronic restraint stress mice. Expression levels of proinflammatory cytokines were tested by QT-PCR and Luminex cytokine assays. The fluorescence-labeled latex beads, flow cytometry and CD68 positive cell counts were utilized to evaluate phagocytic abilities of microglia. Then, the ability of intracerebroventricular injection of STING agonist, 2’3-cGAMP, to reverse the depression-like behaviors and inflammatory cytokines was examined. Results We found that the expression levels of STING, p-TBK1, and p-IRF3 were remarkably decreased in chronic restraint stress mice, which was associated with decreased IFN-β secretion. Moreover, the STING agonist, 2’3-cGAMP, significantly alleviated the neuroinflammation and ameliorated depression-like behavior which depends on the functional STING activation. Furthermore, 2’3-cGAMP promoted microglia phagocytosis through cGAMP-STING-dependent IFN-β release, which was essential for recovery from neuroinflammation during chronic restraint stress. Conclusions These findings demonstrate that STING signaling pathway is a critical mediator in regulating microglia phagocytosis and may serve as a novel therapeutic target for chronic stress-related psychiatric diseases.

scholarly journals Vitamin D Regulatory Effect on Restraint Stress-Induced Changes on Serum Corticosterone and Hippocampus BDNF Levels in Male Rats

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Katayoun Sedaghat ◽  
Sara Choobdar ◽  
Ahmad Reza Bandegi ◽  
Zahra Ghods
Keyword(s):  
Vitamin D ◽  
Chronic Stress ◽  
Restraint Stress ◽  
Male Rats ◽  
Negative Effects ◽  
Bdnf Level ◽  
Serum Corticosterone ◽  
Protein Levels ◽  
Induced Changes ◽  
The Impact

Background: Chronic stress exerts negative effects on cognitive functions through inducing changes in the hippocampus. Brain-derived neurotrophic factor (BDNF) is an essential factor in cognitive activities, which is considerably reduced under chronic stress. 1,25(OH)2 vitamin D plays neuroprotective roles partially by regulating the expression of various neurotrophic factors. Objectives: Since few studies have studied the impact of vitamin D on BDNF level, we conducted this brief experiment to understand the role of vitamin D in maintaining hippocampal BDNF protein levels by using restraint as a model of chronic stress in rats. Methods: Rats underwent restraint stress 3 h/day for 28 days, during which they received vitamin D (5, 10 μg/kg) or its vehicle (IP, twice weekly). After the stress period, serum corticosterone (CORT) and hippocampus BDNF protein levels were measured. Results: Restraint stress increased serum CORT (P < 0.001) and reduced BDNF protein levels (P < 0.001) as compared to the non-stress group. Vitamin D markedly maintained BDNF level close to normal (P < 0.001), but did not change CORT level significantly. Conclusions: This study demonstrated that 3h/day of chronic restraint stress for 28 days boosted serum CORT and declined hippocampal BDNF levels, similar to stronger restraint stress models. Vitamin D maintained BDNF level close to normal in the hippocampus, but it did not affect CORT level significantly.

Mice cohabiting with familiar conspecific in chronic stress condition exhibit methamphetamine-induced locomotor sensitization and augmented consolation behavior.

2021 ◽  
Author(s):  
Paulo Eduardo Carneiro de Oliveira ◽  
Isabela Miranda Carmona ◽  
Mariana Casarotto ◽  
Lara Maria Silveira ◽  
Anna Cecília Bezerra de Oliveira ◽  
...  
Keyword(s):  
Open Field ◽  
Chronic Stress ◽  
Restraint Stress ◽  
Emotional Contagion ◽  
Locomotor Sensitization ◽  
Emotional States ◽  
Species Survival ◽  
Plus Maze ◽  
Repeated Restraint Stress ◽  
Affective Behaviors

Abstract Recognize and share emotions are essential for species survival, but in some cases, living with a conspecific in distress condition may induce negative emotional states through empathy-like processes. Studies have reported that stressors promote psychiatric disorders in both, who suffers directly and who witness these aversive episodes, principally whether social proximity is involved. However, the mechanisms underlying the harmful outcomes of emotional contagion needs more studies, mainly in the drug addiction-related behaviors. Here, we investigated the relevance of familiarity and the effects of cohabitation with a partner submitted to chronic stress in the anxiety-like, locomotor sensitization and consolation behaviors. Male swiss mice were housed in pairs during different periods to test the establishment of familiarity and the stress-induced anxiety behavior in the elevated plus maze. Another cohort was housed with a conspecific subjected to repeated restraint stress (1h/day) for 14 days. During chronic restraint the allogrooming was measured and after the stress period mice were tested in the open field for evaluation of anxiety and locomotor cross-sensitization induced by methamphetamine. We found that familiarity was established after 14 days of cohabitation and the anxiogenic behavior appeared after 14 days of stress. Repeated restraint stress also increased anxiety in the open field test and induced locomotor cross-sensitization in the stressed mice and their cagemates. Cagemates also exhibited increase in consolation behavior after stress sessions when compared to control mice. These results indicate that changes in drug abuse-related, consolation and affective behaviors may be precipitate through emotional contagion in familiar conspecifics.

scholarly journals Housing in Pyramid Counteracts Neuroendocrine and Oxidative Stress Caused by Chronic Restraint in Rats

2007 ◽  
Vol 4 (1) ◽  
pp. 35-42 ◽  
Author(s):  
M. Surekha Bhat ◽  
Guruprasad Rao ◽  
K. Dilip Murthy ◽  
P. Gopalakrishna Bhat
Keyword(s):  
Oxidative Stress ◽  
Hippocampal Neurons ◽  
Plasma Cortisol ◽  
Restraint Stress ◽  
Wire Mesh ◽  
Chronic Restraint Stress ◽  
Energy Field ◽  
The Status ◽  
And Oxidative Stress ◽  
Square Box

The space within the great pyramid and its smaller replicas is believed to have an antistress effect. Research has shown that the energy field within the pyramid can protect the hippocampal neurons of mice from stress-induced atrophy and also reduce neuroendocrine stress, oxidative stress and increase antioxidant defence in rats. In this study, we have, for the first time, attempted to study the antistress effects of pyramid exposure on the status of cortisol level, oxidative damage and antioxidant status in rats during chronic restraint stress. Adult female Wistar rats were divided into four groups as follows: normal controls (NC) housed in home cage and left in the laboratory; restrained rats (with three subgroups) subject to chronic restraint stress by placing in a wire mesh restrainer for 6 h per day for 14 days, the restrained controls (RC) having their restrainers kept in the laboratory; restrained pyramid rats (RP) being kept in the pyramid; and restrained square box rats (RS) in the square box during the period of restraint stress everyday. Erythrocyte malondialdehyde (MDA) and plasma cortisol levels were significantly increased and erythrocyte-reduced glutathione (GSH) levels, erythrocyte glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were significantly decreased in RC and RS rats as compared to NC. However, these parameters were maintained to near normal levels in RP rats which showed significantly decreased erythrocyte MDA and plasma cortisol and significantly increased erythrocyte GSH levels, erythrocyte GSH-Px and SOD activities when compared with RS rats. The results showed that housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats.

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

2016 ◽  
Vol 51 ◽  
pp. 39-46 ◽  
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

Changes in Ribosomal Protein S3 Immunoreactivity and its Protein Levels in the Gerbil Hippocampus Following Subacute and Chronic Restraint Stress

2012 ◽  
Vol 37 (7) ◽  
pp. 1428-1435 ◽  
Author(s):  
Joon Ha Park ◽  
Choong Hyun Lee ◽  
Bing Chun Yan ◽  
Ji Hyeon Ahn ◽  
Young Joo Lee ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Restraint Stress ◽  
Chronic Restraint Stress ◽  
Protein Levels ◽  
Ribosomal Protein S3

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

2021 ◽  
pp. 105083
Author(s):  
Wilasinee Suwanjang ◽  
Waralee Ruankham ◽  
Banthit Chetsawang ◽  
Sujira Mukda ◽  
Sukhonthar Ngampramuan ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Mitochondrial Function ◽  
Restraint Stress ◽  
Chronic Restraint Stress ◽  
Spilanthes Acmella

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

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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