Possible Involvement of the IL-6/JAK2/STAT3 Pathway in the Hypothalamus in Depressive-Like Behavior of Rats Exposed to Chronic Mild Stress

2020 ◽  
pp. 1-9
Author(s):  
Xiaofeng Guan ◽  
Qi Wang ◽  
Mengxi Liu ◽  
Anji Sun ◽  
Xiaobai Li
Keyword(s):  
Chronic Mild Stress ◽  
Janus Kinase ◽  
Mild Stress ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Stat3 Pathway ◽  
Sprague Dawley Rats ◽  
Treatment Of Depression ◽  
Immobility Time ◽  
Swimming Test

<b><i>Introduction:</i></b> The interleukin-6/janus kinase 2/signal transducer and activator of transcription 3 (IL-6/JAK2/STAT3) pathway plays an important role in immune function, but little research has focused on this pathway in depression. We sought to examine the relationship between the IL-6/JAK2/STAT3 pathway and depressive-like behavior. <b><i>Methods:</i></b> Using a chronic mild stress (CMS) paradigm, a total of 36 adult male Sprague-Dawley rats were divided into four matched groups: (1) control + vehicle, (2) CMS + vehicle, (3) control + paroxetine, and (4) CMS + paroxetine. We investigated the effects of CMS on depressive-like behavior by using the forced swimming test (FST). Subsequently, the mRNA levels of members of the IL-6/JAK2/STAT3 pathway were assessed by qRT-PCR. <b><i>Results:</i></b> We found that rats exposed to CMS displayed a significant increase in immobility time and a decrease in climbing time in the FST. Moreover, mRNA levels of IL-6, JAK2, and STAT3 in the hypothalamus were increased following CMS. We also found that mRNA levels of IL-6, JAK2, and STAT3 were normalized by paroxetine administration, which coincided with normalization of the depressive-like behavior. <b><i>Conclusions:</i></b> The IL-6/JAK2/STAT3 pathway may be activated in depression, and targeting this pathway may provide a novel effective therapeutic approach for the treatment of depression.

scholarly journals Aerobic Exercise Prevents Depression via Alleviating Hippocampus Injury in Chronic Stressed Depression Rats

2020 ◽  
Vol 11 (1) ◽  
pp. 9
Author(s):  
Jie Kang ◽  
Di Wang ◽  
Yongchang Duan ◽  
Lin Zhai ◽  
Lin Shi ◽  
...  
Keyword(s):  
Aerobic Exercise ◽  
Mild Stress ◽  
Glutamatergic System ◽  
Sprague Dawley ◽  
Bdnf Expression ◽  
Sprague Dawley Rats ◽  
Immobility Time ◽  
Neurotoxic Effects ◽  
Swimming Test ◽  
Underlying Mechanisms

(1) Background: Depression is one of the overwhelming public health problems. Alleviating hippocampus injury may prevent depression development. Herein, we established the chronic unpredictable mild stress (CUMS) model and aimed to investigate whether aerobic exercise (AE) could alleviate CUMS induced depression-like behaviors and hippocampus injury. (2) Methods: Forty-eight healthy male Sprague-Dawley rats (200 ± 20 g) were randomly divided into 4 groups (control, CUMS, CUMS + 7 days AE, CUMS + 14 days AE). Rats with AE treatments were subjected to 45 min treadmill per day. (3) Results: AE intervention significantly improved CUMS-induced depressive behaviors, e.g., running square numbers and immobility time assessed by the open field and forced swimming test, suppressed hippocampal neuron apoptosis, reduced levels of phosphorylation of NMDA receptor and homocysteine in hippocampus, as well as serum glucocorticoids, compared to the CUMS rats. In contrast, AE upregulated phosphorylation of AMPAR receptor and brain-derived neurotrophic factor (BDNF) hippocampus in CUMS depression rats. The 14 day-AE treatment exhibited better performance than 7 day-AE on the improvement of the hippocampal function. (4) Conclusion: AE might be an efficient strategy for prevention of CUMS-induced depression via ameliorating hippocampus functions. Underlying mechanisms may be related with glutamatergic system, the neurotoxic effects of homocysteine, and/or influences in glucocorticoids-BDNF expression interaction.

scholarly journals Effects of Electroacupuncture on Chronic Unpredictable Mild Stress Rats Depression-Like Behavior and Expression of p-ERK/ERK and p-P38/P38

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jian Xu ◽  
Yanling She ◽  
Ning Su ◽  
Ruixin Zhang ◽  
Lixing Lao ◽  
...  
Keyword(s):  
Forced Swimming Test ◽  
Sucrose Solution ◽  
Chronic Mild Stress ◽  
Forced Swimming ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Sprague Dawley ◽  
Unpredictable Chronic Mild Stress ◽  
Immobility Time ◽  
Swimming Test

We investigate the antidepressant-like effect and mechanism of electroacupuncture (EA) on a chronic unpredictable mild stress rats depression-like behavior. In our study, depression in rats was induced by unpredictable chronic mild stress (UCMS) and isolation for four weeks. Male Sprague-Dawley rats were randomly divided into four groups: Normal, Model, EA, and Sham EA. EA treatment was administered for two weeks, once a day for five days a week. Two acupoints, Yintang (EX-HN3) and Baihui (GV20), were selected. For sham EA, acupuncture needles were inserted shallowly into the acupoints: EX-HN3 and GV20. No electrostimulator was connected. The antidepressant-like effect of the electroacupuncture treatment was measured by sucrose intake test, open field test, and forced swimming test in rats. The protein levels of phosphorylated extracellular regulated protein kinases (p-ERK1/2)/ERK1/2 and p-P38/P38 in the hippocampus (HP) were examined by Western blot analysis. Our data demonstrate that EA treatment decreased the immobility time of forced swimming test and improved the sucrose solution intake in comparison to unpredictable chronic mild stress and placebo sham control. Electroacupuncture may act on depression by enhancing p-ERK1/2 and p-p38 in the hippocampus.

scholarly journals Food Enrichment with Glycyrrhiza glabra Extract Suppresses ACE2 mRNA and Protein Expression in Rats—Possible Implications for COVID-19

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2321
Author(s):  
Daniela Jezova ◽  
Peter Karailiev ◽  
Lucia Karailievova ◽  
Agnesa Puhova ◽  
Harald Murck
Keyword(s):  
Small Intestine ◽  
Chronic Mild Stress ◽  
Glycyrrhiza Glabra ◽  
Entry Point ◽  
Mild Stress ◽  
Sprague Dawley ◽  
Angiotensin Converting Enzyme 2 ◽  
Sprague Dawley Rats ◽  
Mrna And Protein Expression

Angiotensin converting enzyme 2 (ACE2) is a key entry point of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus known to induce Coronavirus disease 2019 (COVID-19). We have recently outlined a concept to reduce ACE2 expression by the administration of glycyrrhizin, a component of Glycyrrhiza glabra extract, via its inhibitory activity on 11beta hydroxysteroid dehydrogenase type 2 (11betaHSD2) and resulting activation of mineralocorticoid receptor (MR). We hypothesized that in organs such as the ileum, which co-express 11betaHSD2, MR and ACE2, the expression of ACE2 would be suppressed. We studied organ tissues from an experiment originally designed to address the effects of Glycyrrhiza glabra extract on stress response. Male Sprague Dawley rats were left undisturbed or exposed to chronic mild stress for five weeks. For the last two weeks, animals continued with a placebo diet or received a diet containing extract of Glycyrrhiza glabra root at a dose of 150 mg/kg of body weight/day. Quantitative PCR measurements showed a significant decrease in gene expression of ACE2 in the small intestine of rats fed with diet containing Glycyrrhiza glabra extract. This effect was independent of the stress condition and failed to be observed in non-target tissues, namely the heart and the brain cortex. In the small intestine we also confirmed the reduction of ACE2 at the protein level. Present findings provide evidence to support the hypothesis that Glycyrrhiza glabra extract may reduce an entry point of SARS-CoV-2. Whether this phenomenon, when confirmed in additional studies, is linked to the susceptibility of cells to the virus requires further studies.

scholarly journals Food Enrichment with Glycyrrhiza Glabra Extract Suppresses ACE2 mRNA and Protein Expression in Rats – Possible Implications for COVID-19

2021 ◽  
Author(s):  
Daniela Jezova ◽  
Peter Karailiev ◽  
Lucia Karailievova ◽  
Agnesa Puhova ◽  
Harald Murck
Keyword(s):  
Small Intestine ◽  
Chronic Mild Stress ◽  
Glycyrrhiza Glabra ◽  
Entry Point ◽  
Mild Stress ◽  
Sprague Dawley ◽  
Angiotensin Converting Enzyme 2 ◽  
Sprague Dawley Rats ◽  
Mrna And Protein Expression

Angiotensin converting enzyme 2 (ACE2) is a key entry point of SARS-CoV-2 virus known to induce COVID-19. We have recently outlined the concept to reduce ACE2 expression by the administration of glycyrrhizin, a component of Glycyrrhiza glabra extract, via its inhibitory activity on 11beta hydroxysteroid dehydrogenase type 2 (11betaHSD2) and resulting activation of mineralocorticoid receptor (MR). We hypothesized that in organs, such as the intestine, which co-express 11betaHSD2, MR and ACE2, the expression of ACE2 would be suppressed. We studied organ tissues from an experiment originally designed to address the effects of Glycyrrhiza glabra extract on the stress response. Male Sprague Dawley rats were left undisturbed or exposed to chronic mild stress for five weeks. For the last two weeks, animals continued with a placebo diet or received a diet containing extract of Glycyrrhiza glabra root at a dose of 150 mg/kg of body weight/day. Quantitative PCR measurements showed a significant decrease in gene expression of ACE2 in the small intestine of rats fed with diet containing Glycyrrhiza glabra extract. This effect was independent of the stress condition and failed to be observed in non-target tissues, namely the heart and the brain cortex. In the small intestine we confirmed the reduction of ACE2 also at the protein level. Present findings provide first evidence to support the hypothesis that Glycyrrhiza glabra extract may reduce an entry point of SARS-CoV-2. Whether this phenomenon, when confirmed in additional studies, is linked to the susceptibility of cells to the virus requires further studies.

scholarly journals Alteration of Behavioral Changes and Hippocampus Galanin Expression in Chronic Unpredictable Mild Stress-Induced Depression Rats and Effect of Electroacupuncture Treatment

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yuping Mo ◽  
Haijiang Yao ◽  
Hongtao Song ◽  
Xin Wang ◽  
Wanshun Chen ◽  
...  
Keyword(s):  
Treatment Options ◽  
Chronic Mild Stress ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Model Group ◽  
Sprague Dawley ◽  
Noninvasive Treatment ◽  
Crossing Numbers ◽  
Sprague Dawley Rats ◽  
Antidepressant Effects

To explore new noninvasive treatment options for depression, this study investigated the effects of electric acupuncture (EA) for depression rat models. Depression in rats was induced by unpredictable chronic mild stress (UCMS) combined with isolation for 21 days. Eighteen male Sprague-Dawley rats were randomly assigned into three groups: control, model, and EA groups. Rats were treated by EA once daily for 21 days. The results showed that body weight and sucrose consumption were significantly increased in EA group than in the model group. The crossing numbers and rearing numbers in the open field test significantly decreased in the model group but not in the EA group. And EA treatments upregulated levels of hippocampus galanin (Gal) in UCMS rats back to relative normal levels. The present study suggested that EA had antidepressant effects on UCMS model rats. The potential antidepressant effect may be related to upregulating Gal expression in hippocampus.

scholarly journals Skeletal Muscle Metabolomic Responses to Endurance and Resistance Training in Rats under Chronic Unpredictable Mild Stress

2021 ◽  
Vol 18 (4) ◽  
pp. 1645
Author(s):  
Xiangyu Liu ◽  
Xiong Xue ◽  
Junsheng Tian ◽  
Xuemei Qin ◽  
Shi Zhou ◽  
...  
Keyword(s):  
Resistance Exercise ◽  
Endurance Exercise ◽  
Field Tests ◽  
Treadmill Running ◽  
Control Group ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Sprague Dawley ◽  
Exercise Interventions ◽  
Sprague Dawley Rats

The objectives of this study were to compare the antidepressant effects between endurance and resistance exercise for optimizing interventions and examine the metabolomic changes in different types of skeletal muscles in response to the exercise, using a rat model of chronic unpredictable mild stress (CUMS)-induced depression. There were 32 male Sprague-Dawley rats randomly divided into a control group (C) and 3 experimental groups: CUMS control (D), endurance exercise (E), and resistance exercise (R). Group E underwent 30 min treadmill running, and group R performed 8 rounds of ladder climbing, 5 sessions per week for 4 weeks. Body weight, sucrose preference, and open field tests were performed pre and post the intervention period for changes in depressant symptoms, and the gastrocnemius and soleus muscles were sampled after the intervention for metabolomic analysis using the 1H-NMR technique. The results showed that both types of exercise effectively improved the depression-like symptoms, and the endurance exercise appeared to have a better effect. The levels of 10 metabolites from the gastrocnemius and 13 metabolites from the soleus of group D were found to be significantly different from that of group C, and both types of exercise had a callback effect on these metabolites, indicating that a number of metabolic pathways were involved in the depression and responded to the exercise interventions.

scholarly journals Antidepressant-Like Effect of Lipid Extract ofChanna striatusin Postpartum Model of Depression in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Mohamed Saleem Abdul Shukkoor ◽  
Mohamad Taufik Hidayat Bin Baharuldin ◽  
Abdul Manan Mat Jais ◽  
Mohamad Aris Mohamad Moklas ◽  
Sharida Fakurazi ◽  
...  
Keyword(s):  
Postpartum Period ◽  
Estradiol Benzoate ◽  
Plasma Corticosterone ◽  
Positive Control ◽  
Lipid Extract ◽  
High Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Malay Population ◽  
Swimming Test

Postpartum depression affects 15% of women.Channa striatus, a freshwater fish, is consumed in local Malay population as a rejuvenating diet during postpartum period. This study evaluated the antidepressant-like effect of lipid extract ofC. striatusfillet and its mechanism of action in female Sprague-Dawley rats in postpartum model of depression. The rats were ovariectomized and treated with high dose of progesterone and estradiol benzoate for 23 days to have hormone-simulated pregnancy. The day 24 and afterwards were considered as the postpartum period. During the postpartum period, lipid extract was administered at 125, 250, and 500 mg/kg through intraperitoneal route for 15 days. Fluoxetine (10 mg/kg) was used as the positive control. On postpartum day 15, the animals were tested in forced swimming test (FST) and open field test (OFT) followed by biochemical analysis. Withdrawal of hormone administration during the postpartum period induced depressive-like behavior in FST. Administration of lipid extract reversed that depressive-like behavior at 125, 250, and 500 mg/kg in FST. In OFT, it decreased the exploratory activity. The mechanism of the antidepressant-like effect may be mediated through the decrease in plasma corticosterone, increase in plasma oxytocin, and decrease in nuclear factor-kappa B in prefrontal cortex of rats.

scholarly journals Differential Effects of Refeeding on Melanocortin-Responsive Neurons in the Hypothalamic Paraventricular Nucleus

Endocrinology ◽  
2008 ◽  
Vol 149 (9) ◽  
pp. 4329-4335 ◽  
Author(s):  
Edith Sánchez ◽  
Praful S. Singru ◽  
Runa Acharya ◽  
Monica Bodria ◽  
Csaba Fekete ◽  
...  
Keyword(s):  
Gene Expression ◽  
Paraventricular Nucleus ◽  
Hypothalamic Paraventricular Nucleus ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Early Action ◽  
Sprague Dawley Rats ◽  
Melanocortin Signaling ◽  
Agouti Related Protein ◽  
Serum Tsh

To explore the effect of refeeding on recovery of TRH gene expression in the hypothalamic paraventricular nucleus (PVN) and its correlation with the feeding-related neuropeptides in the arcuate nucleus (ARC), c-fos immunoreactivity (IR) in the PVN and ARC 2 h after refeeding and hypothalamic TRH, neuropeptide Y (NPY) and agouti-related protein (AGRP) mRNA levels 4, 12, and 24 h after refeeding were studied in Sprague-Dawley rats subjected to prolonged fasting. Despite rapid reactivation of proopiomelanocortin neurons by refeeding as demonstrated by c-fos IR in ARC α-MSH-IR neurons and ventral parvocellular subdivision PVN neurons, c-fos IR was present in only 9.7 ± 1.1% hypophysiotropic TRH neurons. Serum TSH levels remained suppressed 4 and 12 h after the start of refeeding, returning to fed levels after 24 h. Fasting reduced TRH mRNA compared with fed animals, and similar to TSH, remained suppressed at 4 and 12 h after refeeding, returning toward normal at 24 h. AGRP and NPY gene expression in the ARC were markedly elevated in fasting rats, AGRP mRNA returning to baseline levels 12 h after refeeding and NPY mRNA remaining persistently elevated even at 24 h. These data raise the possibility that refeeding-induced activation of melanocortin signaling exerts differential actions on its target neurons in the PVN, an early action directed at neurons that may be involved in satiety, and a later action on hypophysiotropic TRH neurons involved in energy expenditure, potentially mediated by sustained elevations in AGRP and NPY. This response may be an important homeostatic mechanism to allow replenishment of depleted energy stores associated with fasting.

Chronic mild stress induces widespread decreases in thyroid hormone α1 receptor mRNA levels in brain—Reversal by imipramine

2009 ◽  
Vol 34 (2) ◽  
pp. 281-286 ◽  
Author(s):  
Edward J. Stein ◽  
Nylson G. da Silveira Filho ◽  
Danilo C. Machado ◽  
Débora C. Hipólide ◽  
Karen Barlow ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Mrna Levels ◽  
Receptor Mrna

Electroacupuncture Prevents the Depression-Like Behavior by Inhibiting the NF-κB/NLRP3 Inflammatory Pathway in Hippocampus of Mice Subjected to Chronic Mild Stress

2022 ◽  
pp. 1-9
Author(s):  
Qi Wang ◽  
Hongsheng Bi ◽  
Hongfei Huang ◽  
Yitong Wang ◽  
Lili Gong ◽  
...  
Keyword(s):  
Chronic Mild Stress ◽  
Preference Test ◽  
Underlying Mechanism ◽  
Sucrose Preference ◽  
Receptor Protein ◽  
Mild Stress ◽  
Inflammatory Pathway ◽  
Protein Levels ◽  
Tnf Α ◽  
Immobility Time

<b><i>Background:</i></b> The precise physiological mechanisms of acupuncture in the treatment of depression are still unknown. This study aimed to observe the effects of electroacupuncture (EA) on depression-like behavior of mouse in chronic mild stress (CMS) model and explore the underlying mechanism. <b><i>Methods:</i></b> The depression model was established by using CMS method for 6 weeks. After the third week of the CMS paradigm, EA treatment was performed daily for 15 min over a period of 3 weeks. The antidepressant-like effects of EA were evaluated using the sucrose preference test and the forced swimming test (FST). The protein levels of the nuclear factor-kappa B (NF-κB), p-NF-κB, inhibitor of NF-κB, p-IκBα, NOD-like receptor protein 3, interleukin (IL)-6, IL-1β, IL-18, and tumor necrosis factor-α (TNF-α) in hippocampus of mice were detected. <b><i>Results:</i></b> Sucrose preference was decreased after 6 weeks of CMS and the effects of CMS was reversed by EA. CMS increased immobility time and decreased latency to the first immobility in the FST test, but these effects were reversed by EA. CMS-induced nuclear entry of NF-κB (nuclear/cytoplasmic ratio of NF-κB) with an increase in protein levels of p-NF-κB and p-IκBα in the hippocampus. The CMS also increased NLRP3 levels in the hippocampus. However, these effects were reversed by EA. In addition, the levels of IL-6, IL-1β, IL-18, and TNF-α in the hippocampus were increased by CMS, and these effects of stress were reversed by EA. <b><i>Conclusion:</i></b> EA prevented CMS-induced depressive-like behaviors by inhibiting NF-κB/NLRP3 inflammatory pathway.

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