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

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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Protective Effects of Carvacrol against Oxidative Stress Induced by Chronic Stress in Rat’s Brain, Liver, and Kidney

Biochemistry Research International ◽

10.1155/2016/2645237 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 41

Author(s):

Saeed Samarghandian ◽

Tahereh Farkhondeh ◽

Fariborz Samini ◽

Abasalt Borji

Keyword(s):

Oxidative Stress ◽

Restraint Stress ◽

Reduced Glutathione ◽

Control Group ◽

Protective Effects ◽

Chronic Restraint Stress ◽

Oxidative Stress Parameters ◽

Liver And Kidney ◽

Stress Damage ◽

The Brain

Restraint stress may be associated with elevated free radicals, and thus, chronic exposure to oxidative stress may cause tissue damage. Several studies have reported that carvacrol (CAR) has a protective effect against oxidative stress. The present study was designed to investigate the protective effects of CAR on restraint stress induced oxidative stress damage in the brain, liver, and kidney. For chronic restraint stress, rats were kept in the restrainers for 6 h every day, for 21 consecutive days. The animals received systemic administrations of CAR daily for 21 days. To evaluate the changes of the oxidative stress parameters following restraint stress, the levels of malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT) activities were measured in the brain, liver, and kidney. In the stressed animals that received vehicle, the MDA level was significantly higher (P<0.001) and the levels of GSH and antioxidant enzymes were significantly lower than the nonstressed animals (P<0.001). CAR ameliorated the changes in the stressed animals as compared with the control group (P<0.001). This study indicates that CAR can prevent restraint stress induced oxidative damage.

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Chronic restraint stress impairs cognition via modulating HDAC2 expression

Translational Neuroscience ◽

10.1515/tnsci-2020-0168 ◽

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.

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

The American Journal of Chinese Medicine ◽

10.1142/s0192415x18500180 ◽

2018 ◽

Vol 46 (02) ◽

pp. 357-387 ◽

Cited By ~ 8

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.

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Mustard Leaf Extract Suppresses Psychological Stress in Chronic Restraint Stress-Subjected Mice by Regulation of Stress Hormone, Neurotransmitters, and Apoptosis

Nutrients ◽

10.3390/nu12123640 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3640

Author(s):

Kyung-A. Hwang ◽

Hye-Jeong Hwang ◽

Yu Jin Hwang ◽

Young Jun Kim

Keyword(s):

Restraint Stress ◽

Leaf Extract ◽

Caspase 3 ◽

Chronic Restraint Stress ◽

Stress Hormone ◽

Induce Stress ◽

Bdnf Expression ◽

Stress Effects ◽

Cytokine Levels ◽

The Brain

Mustard leaf (Brassica juncea var. crispifolia L. H. Bailey) has been reported to have psychological properties such as anti-depressant activities. However, studies on chronic stress and depression caused by restraint have not been conducted. Therefore, this study aimed to evaluate the effects of a mustard leaf (ML) extract on chronic restraint stress (CRS) in mice. Male mice were subjected to a CRS protocol for a period of four weeks to induce stress. The results showed that the ML extract (100 and 500 mg/kg/perorally administered for four weeks) significantly decreased corticosterone levels and increased neurotransmitters levels in stressed mice. Apoptosis by CRS exposure was induced by Bcl-2 and Bax expression regulation and was suppressed by reducing caspase-3 and poly (ADP-ribose) polymerase expression after treatment with the ML extract. Our results confirmed that apoptosis was regulated by increased expression of brain-derived neurotrophic factor (BDNF). Additionally, cytokine levels were regulated by the ML extract. In conclusion, our results showed that the ML extract relieved stress effects by regulating hormones and neurotransmitters in CRS mice, BDNF expression, and apoptosis in the brain. Thus, it can be suggested that the studied ML extract is an agonist that can help relieve stress and depression.

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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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Protective effects of S-allyl cysteine on behavioral, morphological and biochemical alterations in rats subjected to chronic restraint stress: Antioxidant and anxiolytic effects

Journal of Functional Foods ◽

10.1016/j.jff.2017.05.034 ◽

2017 ◽

Vol 35 ◽

pp. 105-114 ◽

Cited By ~ 3

Author(s):

Hugo Becerril-Chávez ◽

Ana Laura Colín-González ◽

Juana Villeda-Hernández ◽

Sonia Galván-Arzate ◽

Anahí Chavarría ◽

...

Keyword(s):

Restraint Stress ◽

Protective Effects ◽

Chronic Restraint Stress ◽

Biochemical Alterations

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Protection Against Blood-brain Barrier Permeability as a Possible Mechanism for Protective Effects of Thymoquinone Against Sickness Behaviors Induced by Lipopolysaccharide in Rats

Jundishapur Journal of Natural Pharmaceutical Products ◽

10.5812/jjnpp.67765 ◽

2021 ◽

Vol 16 (2) ◽

Author(s):

Rahimeh Bargi ◽

Mahmoud Hosseini ◽

Fereshteh Asgharzadeh ◽

Majid Khazaei ◽

Mohammad Naser Shafei ◽

...

Keyword(s):

Blood Brain Barrier ◽

Active Role ◽

Brain Barrier ◽

Control Group ◽

Protective Effects ◽

Blood Brain ◽

Immobility Time ◽

Sickness Behaviors ◽

Bbb Permeability ◽

The Brain

Background: Blood-brain barrier (BBB), as well-known protection for the brain, plays an active role in normal homeostasis. It might be changed by a range of inflammatory mediators to have a role in sickness behaviors. Objectives: Regarding the anti-inflammatory effects of thymoquinone (TQ), its protection against BBB permeability, as a possible mechanism for protective effects against sickness behaviors elicited by lipopolysaccharide (LPS), was evaluated in rats. Methods: The animals were grouped as follows and treated (n = 10 in each): (1) control (saline); (2) LPS 1 mg/kg, was injected two hours before behavioral tests for two weeks; (3-5) 2, 5, and 10 mg/kg TQ, respectively was injected 30 min before LPS injection. Open-field (OF), elevated plus-maze (EPM) and Forced Swimming test (FST) were done. Finally, the animals were anesthetized to evaluate for BBB permeability using Evans blue (EB) dye method. Results: Compared with control, LPS decreased the peripheral distance and crossing and also total crossing and distance in OF, (P < 0.01 - P < 0.001). The central crossing and distance and central time in all three treatment groups were more than LPS (P < 0.05 - P < 0.001). LPS also reduced the entries and the time spent in the open arm while increased the time spent in the closed arm in EPM (P < 0.05 - P < 0.001). The effects of LPS were reversed by TQ (P < 0.05 - P < 0.001). In FST, the immobility time and active time were increased and decreased by LPS compared with control (P < 0.001), respectively. In all three TQ-treated groups, the active and climbing times were more while the immobility time was fewer than the LPS (P < 0.05 - P < 0.001). The animals of the LPS group showed more EB dye content in their brain tissue than the control group (P < 0.05 - P < 0.001). TQ significantly reduced EB dye content of the brain tissues (P < 0.05 - P < 0.001). Conclusions: According to this study, protection against BBB permeability as a possible mechanism for the protective effects of TQ against sickness behaviors induced by LPS might be suggested.

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