scholarly journals Antidepressant-like Effects of Combined Fluoxetine and Zinc Treatment in Mice Exposed to Chronic Restraint Stress Are Related to Modulation of Histone Deacetylase

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 22
Author(s):  
Paulina Misztak ◽  
Magdalena Sowa-Kućma ◽  
Patrycja Pańczyszyn-Trzewik ◽  
Bernadeta Szewczyk ◽  
Gabriel Nowak
Keyword(s):  
Depressive Symptoms ◽  
Histone Deacetylase ◽  
Restraint Stress ◽  
Behavioral Assessment ◽  
Combined Treatment ◽  
Brain Structures ◽  
Chronic Restraint Stress ◽  
Immobility Time ◽  
Key Factor ◽  
Inflammatory Processes

Chronic stress is the key factor contributing to the development of depressive symptoms. Chronic restraint stress (CRS) is well validated and is one of the most commonly used models to induce depressive-like behavior in rodents. The present study aimed to evaluate whether fluoxetine (FLU 5 mg/kg) and zinc (Zn 10mg/kg) given simultaneously induce a more pronounced antidepressant-like effect in the CRS model than both those compounds given alone. Behavioral assessment was performed using the tail suspension and splash tests (TST and ST, respectively). Furthermore, the effects of CRS, FLU and Zn given alone and combined treatment with FLU + Zn on the expression of proteins involved in the apoptotic, inflammatory, and epigenetic processes were evaluated in selected brain structures (prefrontal cortex, PFC; and hippocampus, Hp) using Western blot analysis or enzyme-linked immunosorbent assays (ELISA). The results obtained indicated that three hours (per day) of immobilization for 4 weeks induced prominent depressive symptoms that manifested as increased immobility time in the TST, as well as decreased number and grooming time in the ST. Behavioral changes induced by CRS were reversed by both FLU (5 and 10 mg/kg) or Zn (10 mg/kg). Zinc supplementation (10 mg/kg) slightly increases the effectiveness of FLU (5 mg/kg) in the TST. However, it significantly increased the activity of FLU in the ST compared to the effect induced by FLU and Zn alone. Biochemical studies revealed that neither CRS nor FLU and Zn given alone or in combined treatment alter the expression of proteins involved in apoptotic or inflammatory processes. CRS induced major alterations in histone deacetylase (HDAC) levels by increasing the level of HADC1 and decreasing the level of HADC4 in the PFC and Hp, decreasing the level of HADC6 in the PFC but increasing it in Hp. Interestingly, FLU + Zn treatment reversed CRS-induced changes in HDAC levels in the Hp, indicating that HDAC modulation is linked to FLU + Zn treatment and this effect is structure-specific.

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.

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

2018 ◽  
Vol 17 (5) ◽  
pp. 361-369 ◽  
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.

scholarly journals Rubrofusarin Attenuates Chronic Restraint Stress-Induced Depressive Symptoms

2020 ◽  
Vol 21 (10) ◽  
pp. 3454
Author(s):  
Jee Hyun Yi ◽  
Jieun Jeon ◽  
Huiyoung Kwon ◽  
Eunbi Cho ◽  
Jeanho Yun ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Restraint Stress ◽  
Glycogen Synthase ◽  
Adaptor Protein ◽  
Long Term Potentiation ◽  
Chronic Restraint Stress ◽  
Akt Inhibitor ◽  
Pyrin Domain ◽  
Fluoro Jade B

The aim of this study was to examine whether rubrofusarin, an active ingredient of the Cassia species, has an antidepressive effect in chronic restraint stress (CRS) mouse model. Although acute treatment using rubrofusarin failed, chronic treatment using rubrofusarin ameliorated CRS-induced depressive symptoms. Rubrofusarin treatment significantly reduced the number of Fluoro-Jade B-positive cells and caspase-3 activation within the hippocampus of CRS-treated mice. Moreover, rubrofusarin treatment significantly increased the number of newborn neurons in the hippocampus of CRS-treated mice. CRS induced activation of glycogen synthase kinase-3β and regulated development and DNA damage responses, and reductions in the extracellular-signal-regulated kinase pathway activity were also reversed by rubrofusarin treatment. Microglial activation and inflammasome markers, including nod-like receptor family pyrin domain containing 3 and adaptor protein apoptosis-associated speck-like protein containing CARD, which were induced by CRS, were ameliorated by rubrofusarin. Synaptic plasticity dysfunction within the hippocampus was also rescued by rubrofusarin treatment. Within in vitro experiments, rubrofusarin blocked corticosterone-induced long-term potentiation impairments. These were blocked by LY294002, which is an Akt inhibitor. Finally, we found that the antidepressant effects of rubrofusarin were blocked by an intracerebroventricular injection of LY294002. These results suggest that rubrofusarin ameliorated CRS-induced depressive symptoms through PI3K/Akt signaling.

scholarly journals Preliminary behavioral assessment of cagemates living with conspecifics submitted to chronic restraint stress in mice

2017 ◽  
Vol 657 ◽  
pp. 204-210 ◽  
Author(s):  
P.E. Carneiro de Oliveira ◽  
Caroline R. Zaniboni ◽  
Isabela M. Carmona ◽  
Aura R. Fonseca ◽  
Azair Canto-de-Souza
Keyword(s):  
Restraint Stress ◽  
Behavioral Assessment ◽  
Chronic Restraint Stress

Behavioral effects and CRF expression in brain structures of high- and low-anxiety rats after chronic restraint stress

2016 ◽  
Vol 310 ◽  
pp. 26-35 ◽  
Author(s):  
Aleksandra Wisłowska-Stanek ◽  
Małgorzata Lehner ◽  
Anna Skórzewska ◽  
Paweł Krząścik ◽  
Adam Płaźnik
Keyword(s):  
Restraint Stress ◽  
Brain Structures ◽  
Behavioral Effects ◽  
Chronic Restraint Stress

scholarly journals The Alterations of IL-1Beta, IL-6, and TGF-Beta Levels in Hippocampal CA3 Region of Chronic Restraint Stress Rats after Electroacupuncture (EA) Pretreatment

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Tianwei Guo ◽  
Zhuo Guo ◽  
Xinjing Yang ◽  
Lan Sun ◽  
Sihan Wang ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Restraint Stress ◽  
Depressive Disorders ◽  
Open Field Test ◽  
Underlying Mechanism ◽  
Chronic Restraint Stress ◽  
Tgf Beta ◽  
Hippocampal Ca3 ◽  
Immunological Reactions ◽  
Ca3 Region

Immunological reactions induced by proinflammatory cytokines have been involved in the pathogenesis of depressive disorders. Recent studies showed that Electroacupuncture (EA) was able to reduce depressive symptoms; however, the underlying mechanism and its potential targets remain unknown. In the present study, we used a 21-day chronic restraint stress rats as a model to investigate how EA could alleviate depression. Open field test was carried out to evaluate the depressive symptoms at selected time points. At the end of study, immunohistochemistry (IHC) was performed to detect the expressions of IL-1beta, IL-6, and TGF-beta in hippocampal CA3 region. We found that chronic restraint stress significantly decreased behavioral activities, whereas EA stimulation at points Baihui (GV 20) and Yintang (GV 29) showed protective effect during the test period. In addition, the IL-1beta, IL-6, and TGF-beta increased in rats exposed to chronic restraint stress, while EA downregulated the levels of IL-1beta and IL-6. These findings implied that EA pretreatment could alleviate depression through modulating IL-1beta and IL-6 expression levels in hippocampal CA3 region.

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.

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