scholarly journals Escitalopram Targets Oxidative Stress, Caspase-3, BDNF and MeCP2 in the Hippocampus and Frontal Cortex of a Rat Model of Depression Induced by Chronic Unpredictable Mild Stress

2021 ◽  
Vol 22 (14) ◽  
pp. 7483
Author(s):  
Vlad Dionisie ◽  
Adela Magdalena Ciobanu ◽  
Vlad Alexandru Toma ◽  
Mihnea Costin Manea ◽  
Ioana Baldea ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Frontal Lobe ◽  
Caspase 3 ◽  
Preference Test ◽  
Sucrose Preference ◽  
Fixed Dose ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Sucrose Preference Test

In recent years, escitalopram (ESC) has been suggested to have different mechanisms of action beyond its well known selective serotonin reuptake inhibition. The aim of this study is to investigate the effects of escitalopram on oxidative stress, apoptosis, brain-derived neurotrophic factor (BDNF), Methyl-CpG-binding protein 2 (MeCP2), and oligodendrocytes number in the brain of chronic unpredictable mild stress-induced depressed rats. The animals were randomised in four groups (8 in each group): control, stress, stress + ESC 5 and stress + ESC 5/10. ESC was administered for 42 days in a fixed dose (5 mg/kg b.w.) or in an up-titration regimen (21 days ESC 5 mg/kg b.w. then 21 days ESC 10 mg/kg b.w.). Sucrose preference test (SPT) and elevated plus maze (EPM) were also performed. ESC improved the percentage of sucrose preference, locomotion and anxiety. ESC5/10 reduced the oxidative damage in the hippocampus and improved the antioxidant defence in the hippocampus and frontal lobe. ESC5/10 lowered caspase 3 activity in the hippocampus. Escitalopram had a modulatory effect on BDNF and the number of oligodendrocytes in the hippocampus and frontal lobe and also improved the MeCP2 expressions. The results confirm the multiple pathways implicated in the pathogenesis of depression and suggest that escitalopram exerts an antidepressant effect via different intricate mechanisms.

scholarly journals The Antidepressant Effect ofAngelica sinensisExtracts on Chronic Unpredictable Mild Stress-Induced Depression Is Mediated via the Upregulation of the BDNF Signaling Pathway in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Jun Shen ◽  
Junjian Zhang ◽  
Min Deng ◽  
Yue Liu ◽  
Yuan Hu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Preference Test ◽  
Camp Response Element Binding ◽  
Sucrose Preference ◽  
Antidepressant Effect ◽  
Force Swim Test ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Traditional Chinese Herbal Medicine ◽  
Bdnf Signaling

Angelica sinensis(AS), a traditional Chinese herbal medicine, has pharmaceutical effects on menstrual illness, cerebrovascular diseases, cardiovascular diseases, and cognitive impairments. However, until recently, few studies had explored its antidepressant effect. The current study attempts to investigate the effect of AS extracts on chronic unpredictable mild stress- (CUMS-) induced depression in rats. Male SD rats were exposed to a CUMS-inducing procedure for 5 weeks, resulting in rodent depressive behaviors that included reduced sucrose consumption and lessened sucrose preference ratios in sucrose preference test, prolonged immobility times and decreased struggling time in force swim test, and decreased locomotor activity in open field test. Moreover, the expression of brain derived neurotrophic factor (BDNF) and the phosphorylation of cAMP-response element binding protein (CREB) and extracellular signal-regulated protein kinase (ERK 1/2) were markedly decreased in the hippocampus in depressed rats. However, chronically treating the depressed rats with AS (1 g/kg) normalized their depression-related behaviors and molecular profiles. In conclusion, in the present study, we show that AS extracts exerted antidepressant effects that were mediated by the BDNF signaling pathway: in AS-treated depressed rats, the expression of the BDNF protein and the phosphorylation of its downstream targets (ERK 1/2, CREB) were upregulated in the hippocampus.

scholarly journals Crassifoside H ameliorates depressant behavior in chronic unpredictable mild stress rats by improving HPA axis dysfunction and inhibiting inflammation in hippocampus

2020 ◽  
Vol 19 (8) ◽  
pp. 1693-1699
Author(s):  
Huina Li ◽  
Kefan Wu ◽  
Yue Zhang ◽  
Ning Li ◽  
Kaijin Wang
Keyword(s):  
Hpa Axis ◽  
Mechanism Of Action ◽  
Therapeutic Potential ◽  
Preference Test ◽  
Antidepressant Effect ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Tnf Α ◽  
Sucrose Preference Test

Purpose: To investigate the antidepressant mechanism of action of Crassifoside H (CH) from the rhizomes of Curculigo glabrescens (Hypoxidaceae) in chronic unpredictable mild stress (CUMS)-induced rats.Methods: CUMS-induced rat depressant model was established. Behavioral tests, viz, sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST) were applied to assess the antidepressant effect of CH. Enzyme linked immunosorbent assay (ELISA) was used to assess thelevels of corticosterone (CORT), TNF-α and IL-1β in serum. Protein expressions of TNF-α, IL-1β and NLRP3 in rat hippocampus were determined by Western blot.Results: Crassifoside H significantly ameliorated CUMS-induced depressant-like behavior as the serum CORT level of CUMS rats. CH remarkably decreased TNF-α and IL-1β levels in serum and hippocampus of CUMS rats. Moreover, Crassifoside H significantly inhibited NLRP3 activation inhippocampus.Conclusion: The findings demonstrate that Crassifoside H has antidepressant effect on CUMS rats. The mechanism of action of CH may be at least partly due to the improvement of hypothalamic-pituitaryadrenal (HPA) axis dysfunction by decreasing serum CORT. These findings suggest that Crassifoside H has a therapeutic potential for the management of depression. Keywords: Crassifoside H, Antidepression, Curculigo glabrescens, Hypoxidaceae, Hypothalamicpituitary- adrenal axis, Inflammation, Corticosterone

scholarly journals The Combination of Aquilaria sinensis (Lour.) Gilg and Aucklandia costus Falc. Volatile Oils Exerts Antidepressant Effects in a CUMS-Induced Rat Model by Regulating the HPA Axis and Levels of Neurotransmitters

2021 ◽  
Vol 11 ◽  
Author(s):  
Huiting Li ◽  
Yuanhui Li ◽  
Xiaofei Zhang ◽  
Guilin Ren ◽  
Liangfeng Wang ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Central Area ◽  
Preference Test ◽  
Volatile Oil ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Aquilaria Sinensis ◽  
Immobility Time ◽  
The Central Nervous System ◽  
Sucrose Preference Test

The Aquilaria sinensis (Lour.) Gilg (CX)–Aucklandia costus Falc. (MX) herbal pair is frequently used in traditional Chinese medicine prescriptions for treating depression. The volatile oil from CX and MX has been shown to have good pharmacological activities on the central nervous system, but its curative effect and mechanism in the treatment of depression are unclear. Therefore, the antidepressant effect of the volatile oil from CX–MX (CMVO) was studied in chronic unpredictable mild stress (CUMS) rats. The suppressive effects of CMVO (25, 50, 100 μL/kg) against CUMS-induced depression-like behavior were evaluated using the forced swimming test (FST), open field test (OFT) and sucrose preference test (SPT). The results showed that CMVO exhibited an antidepressant effect, reversed the decreased sugar preference in the SPT and prolongation of immobility time in the FST induced by CUMS, increased the average speed, time to enter the central area, total moving distance, and enhanced the willingness of rats to explore the environment in the OFT. Inhalational administration of CMVO decreased levels of adrenocorticotropic hormone and corticosterone in serum and the expression of corticotropin-releasing hormone mRNA in the hypothalamus, which indicated regulation of over-activation of the hypothalamic–pituitary–adrenal (HPA) axis. In addition, CMVO restored levels of 5-hydroxytryptamine (5-HT), dopamine, norepinephrine and acetylcholine in the hippocampus. The RT-PCR and immunohistochemistry results showed that CMVO up-regulated the expression of 5-HT1A mRNA. This study demonstrated the antidepressant effect of CMVO in CUMS rats, which was possibly mediated via modulation of monoamine and cholinergic neurotransmitters and regulation of the HPA axis.

scholarly journals NLRP1-Mediated Antidepressant Effect of Ketamine in Chronic Unpredictable Mild Stress Model in Rats

2020 ◽  
Vol 17 (4) ◽  
pp. 283-291 ◽  
Author(s):  
Feyza Aricioğlu ◽  
Canan Yalcinkaya ◽  
Ceren Sahin Ozkartal ◽  
Erdem Tuzun ◽  
Serap Sirvanci ◽  
...  
Keyword(s):  
Preference Test ◽  
Receptor Protein ◽  
Antidepressant Effect ◽  
Albino Rats ◽  
Depression Symptoms ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Nlrp1 Inflammasome ◽  
Immobility Time ◽  
Wistar Albino Rats

Objective NOD-like receptor protein 1 (NLRP1) inflammasome complex has been recently associated with chronic unpredictable mild stress (CUMS) model of depression. Our aim was to investigate whether ketamine-induced antidepressant effect is associated with suppression of NLRP1.Methods Wistar albino rats were divided into control, CUMS, CUMS+acute ketamine (a single 10 mg/kg dose) and CUMS+chronic ketamine (daily 10 mg/kg injections for 3 weeks) groups (n=10 for each group). Sucrose preference test and forced swimming test were performed to assess anhedonia and immobility time respectively for the severety of depression symptoms. Brain tissues were dissected and prefrontal cortex and hippocampus regions were used for real-time polymerase chain reaction (PCR) and immunohistochemical analysis.Results CUMS procedure significantly induced depressive-like symptoms whereas both acute and chronic ketamine treatment ameliorated them. mRNA expression levels of NLRP1, caspase 1, apoptosis-associated speck-like protein containing a CARD (ASC), NF-κB, endothelial nitric oxide synthase, IL-1β, IL-6, toll-like receptor 4 (TLR-4) and purinergic 2×7 receptor (P2X7R) and numbers of Iba- 1+and GFAP+glial cells were reduced by acute and/or chronic ketamine treatment.Conclusion In the present study for the first time upstream and downstream elements of the NLRP1 inflammasome complex are shown to be suppressed by ketamine thus reinforcing the involvement of NLRP1 in the physiopathology of depression.

scholarly journals ANTIDEPRESSANT-LIKE ACTIVITY OF TRANS-ANETHOLE IN UNSTRESSED MICE AND STRESSED MICE

2019 ◽  
pp. 121-127
Author(s):  
DINESH DHINGRA ◽  
SUDHA
Keyword(s):  
Preference Test ◽  
Tail Suspension Test ◽  
Plasma Corticosterone ◽  
Monoamine Oxidase A ◽  
Sucrose Preference ◽  
Mild Stress ◽  
Male Mice ◽  
Mao A ◽  
Sucrose Preference Test ◽  
Plasma Nitrite

Objectives: The present study was undertaken to investigate the antidepressant potential of trans-anethole in unstressed and stressed male mice. Methods: Swiss albino male mice were exposed to chronic unpredictable mild stress for 21 successive days. Simultaneously, trans-anethole (12.5 mg/kg, 25 mg/kg, and 50 mg/kg) and fluoxetine (20 mg/kg) per se were administered for 21 successive days to separate groups of unstressed and stressed mice. The effect of drugs on depressive-like behavior of mice was tested by tail suspension test (TST) and sucrose preference test. Results: Trans-anethole (25 mg/kg) and fluoxetine significantly decreased the immobility period of unstressed and stressed mice in TST as compared to their respective control. These drugs significantly restored the reduced sucrose preference (%) in stressed mice. Trans-anethole did not show any significant effect on locomotor activity of mice. Antidepressant-like activity of trans-anethole (25 mg/kg) was found to be comparable to fluoxetine. Trans-anethole and fluoxetine significantly inhibited brain monoamine oxidase-A (MAO-A) activity, decreased plasma nitrite, brain malondialdehyde, and increased brain reduced glutathione levels and catalase activity in unstressed and stressed mice. The drugs significantly reversed stress-induced increase in plasma corticosterone levels. Conclusion: Trans-anethole produced significant antidepressant-like activity in unstressed and stressed mice, possibly through inhibition of brain MAO-A activity and alleviation of oxidative stress. Reversal of stress-induced increase in plasma corticosterone levels might also be responsible for antidepressant-like activity of trans-anethole in stressed mice.

scholarly journals ANTIDEPRESSANT-LIKE ACTIVITY OF FLOWERS OF TECOMELLA UNDULATA IN MICE SUBJECTED TO CHRONIC UNPREDICTABLE MILD STRESS

2019 ◽  
Vol 12 (1) ◽  
pp. 130
Author(s):  
Dinesh Dhingra ◽  
Deepak Deepak
Keyword(s):  
Young Male ◽  
Ethanol Extract ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Plasma Corticosterone ◽  
Sucrose Preference ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Tecomella Undulata ◽  
Plasma Nitrite

Objective: Flowers of Tecomella undulata have been reported to be a rich source of flavonoids such as rutin and quercetin. The present study was designed to evaluate the effect of ethanol extract of flowers of T. undulata on chronic unpredictable mild stress (CUMS)-induced depression in Swiss young male albino mice.Methods: The mice were subjected to CUMS for 21 successive days. Ethanol extract of the flowers (50, 100, and 200 mg/kg, p.o.) and fluoxetine (20 mg/kg, p.o.) per se was administered for 21 successive days to separate groups of unstressed and stressed mice. Tail suspension test (TST) and sucrose preference test were used to evaluate the effect of the extract on depression-like behavior in mice.Results: Extract of flowers of T. undulata (100 and 200 mg/kg) significantly decreased immobility period of stressed mice in TST, indicating significant antidepressant-like activity of the extract. Stress-induced reduced sucrose preference was significantly restored by the extract. There was no significant effect on locomotor activity of mice by the extract and fluoxetine. The extract significantly reversed stress-induced increase in brain malondialdehyde levels; plasma nitrite and corticosterone levels; and also significantly reversed the stress-induced decrease in reduced glutathione and catalase levels. There was no significant effect of the extract on brain MAO-A activity in both unstressed and stressed mice.Conclusion: These results indicated that ethanol extract of flowers of T. undulata showed significant antidepressant-like activity in mice subjected to CUMS, probably through alleviation of oxidative stress and decrease in plasma corticosterone levels.

scholarly journals The Antidepressant-Like Effects of Shen Yuan in a Chronic Unpredictable Mild Stress Rat Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Ning Jiang ◽  
Haixia Wang ◽  
Hong Huang ◽  
Jingwei Lv ◽  
Guirong Zeng ◽  
...  
Keyword(s):  
Panax Ginseng ◽  
Forced Swim Test ◽  
Preference Test ◽  
Underlying Mechanism ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Oxidative Markers ◽  
Immobility Time ◽  
Polygala Tenuifolia ◽  
Sucrose Preference Test

Depression is a common yet severe neuropsychiatric condition that causes imposes considerable personal, economic, and social burdens worldwide. Medicinal plant species (e.g., Panax ginseng and Polygala tenuifolia) demonstrate potent antidepressant-like effects with less toxicity and other side effects. Shen yuan prescription (SY), composed of Panax ginseng (GT) and Polygala tenuifolia (YT). The present study aimed to elucidate the effects of SY treatment on chronic unpredictable mild stress (CUMS) rats and study the underlying mechanism. Our results indicated that SY (67.5, 135, or 270 mg/kg) significantly reverses the depressive-like behaviors in rats with a 5-week CUMS exposure, as demonstrated by increased sucrose consumption in the sucrose preference test, and decreased immobility time in the tail suspension and forced swim test. Moreover, SY altered serum corticosterone levels, pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), and oxidative markers (SOD, CAT, and MDA), and increased the levels of hippocampal neurotransmitters (5-HT, DA, and NE) in rats exposed to CUMS. Furthermore, rats treated with SY showed a reduction in the protein expression of BDNF, p-TrkB, p-Akt, and p-mTOR proteins induced by CUMS exposure in the hippocampus. In conclusion, SY prevented depressive-like behaviors in CUMS-exposed rats by preventing hypothalamus-pituitary-adrenal axis dysfunction, decreasing the levels of the neurotransmitters, minimizing oxidative stress, suppressing neuroinflammation, and activating the PI3K/Akt/mTOR-mediated BDNF/TrkB pathway, all of which are the key players in the pathological basis of depression.

scholarly journals Curcumin Attenuates Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors via Restoring Changes in Oxidative Stress and the Activation of Nrf2 Signaling Pathway in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Dehua Liao ◽  
Chuanfeng Lv ◽  
Lizhi Cao ◽  
Dunwu Yao ◽  
Yi Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Spine Density ◽  
Related Protein ◽  
Stress Markers ◽  
Dendritic Length ◽  
Nrf2 Signaling Pathway

Accumulating evidence has demonstrated that oxidative stress is associated with depression. Our present study aimed at investigating the antidepressant effect and the possible mechanisms of curcumin (CUR) in chronic unpredictable mild stress- (CUMS-) induced depression model in rats. After exposure to CUMS for four weeks, the rats showed depressive-like behavior, and the depressive-like behaviors in CUMS-treated rats were successfully corrected after administration of CUR. In addition, CUR could effectively decrease protein expression of oxidative stress markers (Nox2, 4-HNE, and MDA) and increase the activity of CAT. CUR treatment also reversed CUMS-induced inhibition of Nrf2-ARE signaling pathway, along with increasing the mRNA expression of NQO-1 and HO-1. Furthermore, the supplementation of CUR also increased the ratio of pCREB/CREB and synaptic-related protein (BDNF, PSD-95, and synaptophysin). In addition, CUR could effectively reverse CUMS-induced reduction of spine density and total dendritic length. In conclusion, the study revealed that CUR relieves depressive-like state through the mitigation of oxidative stress and the activation of Nrf2-ARE signaling pathway.

scholarly journals The Antidepressant Effect of Chlorella vulgaris on Female Wistar Rats (Rattus norvegicus Berkenhout, 1769) with Chronic Unpredictable Mild Stress Treatment

2019 ◽  
Vol 4 (2) ◽  
pp. 72
Author(s):  
Gisella Intan Soetantyo ◽  
Mulyati Sarto
Keyword(s):  
Chlorella Vulgaris ◽  
Adrenal Glands ◽  
Forced Swim Test ◽  
Female Rats ◽  
Sucrose Preference ◽  
World Health ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Duration Of Treatment

Depression is a disabling mental disorder, predicted to become the world's number 2 disability by 2020 by the World Health Organization (WHO, 2018). Chronic stress is one of the triggers for depression, causing an imbalance in brain chemicals and antioxidants levels. Although antidepressant is a common treatment, discomforting side effects has compromised its efficacy, prompting the search for alternative medicines. Chlorella vulgaris is a microalgae famous for its excellent protein and antioxidant content. In this study, C. vulgaris (360 mg/kg p.o.) potency of antidepressant in chronic unpredictable mild stress (CUMS) model of depression in female rats was evaluated compared to amitriptyline (2,25 mg/kg p.o.) for 14 days. Two types of C. vulgaris namely cultivation sourced and commercially-sold, were used. Sucrose preference test, forced swim test (FST) and open field test (OFT) were used as depression-like behaviour test to validate C. vulgaris effect. Adrenal glands were observed to further understand its effect on the stress organ. The CUMS method produced rats with depressive-like behaviour evidently by reduced body weight, sucrose preference, exploring behaviour in OFT, and increased immobility duration in FST. Furthermore, an increase in adrenal weight, fasciculata zone, and reticularis zone was observed. Both C. vulgaris significantly (p<0,05) reversed depressive-like behaviour in rats subjected to CUMS, but not the size of adrenal glands. This finding indicated both types of C. vulgaris has the potential to be an alternative antidepressant but because of the short duration of treatment, it’s speculated that C. vulgaris may not have exhibited enough difference structurally yet. 

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