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  1. Fulltext The association between polyunsaturated fatty acids and depression among Iranian postgraduate students in Malaysia
    Yary T, Aazami S
    Lipids Health Dis, 2011;10:151.
    PMID: 21864357 DOI: 10.1186/1476-511X-10-151
    The incidence of depression is expected to increase over the next 20 years, and many people will have to deal with it. It has been reported that up to 40% of university students experience levels of depression. Several negative consequences are associated with depression symptoms, such as memory impairment, suicide, and substance abuse. Recently, researchers have been studying possible associations between depression and polyunsaturated fatty acids (PUFAs), which may modify depression symptoms. The aim of the present study was to find an association between PUFA levels and depression among Iranian postgraduate students in Malaysia.
    Matched MeSH terms: Depression/metabolism
  2. Fulltext Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms
    Lim LW, Prickaerts J, Huguet G, Kadar E, Hartung H, Sharp T, et al.
    Transl Psychiatry, 2015;5:e535.
    PMID: 25826110 DOI: 10.1038/tp.2015.24
    Deep brain stimulation (DBS) is a promising therapy for patients with refractory depression. However, key questions remain with regard to which brain target(s) should be used for stimulation, and which mechanisms underlie the therapeutic effects. Here, we investigated the effect of DBS, with low- and high-frequency stimulation (LFS, HFS), in different brain regions (ventromedial prefrontal cortex, vmPFC; cingulate cortex, Cg; nucleus accumbens (NAc) core or shell; lateral habenula, LHb; and ventral tegmental area) on a variety of depressive-like behaviors using rat models. In the naive animal study, we found that HFS of the Cg, vmPFC, NAc core and LHb reduced anxiety levels and increased motivation for food. In the chronic unpredictable stress model, there was a robust depressive-like behavioral phenotype. Moreover, vmPFC HFS, in a comparison of all stimulated targets, produced the most profound antidepressant effects with enhanced hedonia, reduced anxiety and decreased forced-swim immobility. In the following set of electrophysiological and histochemical experiments designed to unravel some of the underlying mechanisms, we found that vmPFC HFS evoked a specific modulation of the serotonergic neurons in the dorsal raphe nucleus (DRN), which have long been linked to mood. Finally, using a neuronal mapping approach by means of c-Fos expression, we found that vmPFC HFS modulated a brain circuit linked to the DRN and known to be involved in affect. In conclusion, HFS of the vmPFC produced the most potent antidepressant effects in naive rats and rats subjected to stress by mechanisms also including the DRN.
    Matched MeSH terms: Depression/metabolism
  3. Repressor element 1 silencing transcription factor /neuron-restrictive silencing factor (REST/NRSF) in social stress and depression
    Soga T, Nakajima S, Kawaguchi M, Parhar IS
    Prog Neuropsychopharmacol Biol Psychiatry, 2021 01 10;104:110053.
    PMID: 32739332 DOI: 10.1016/j.pnpbp.2020.110053
    Extreme stress is closely linked with symptoms of depression. Chronic social stress can cause structural and functional changes in the brain. These changes are associated with dysfunction of neuroprotective signalling that is necessary for cell survival, growth, and maturation. Reduced neuronal numbers and volume of brain regions have been found in depressed patients, which may be caused by decreased cell survival and increased cell death. Elucidating the mechanism underlying the degeneration of the neuroprotective system in social stress-induced depression is important for developing neuroprotective measures. The Repressor Element 1 Silencing Transcription Factor (REST) also known as Neuron-Restrictive Silencing Factor (NRSF) has been reported as a neuroprotective molecule in certain neurological disorders. Decreased expression levels of REST/NRSF in the nucleus can induce death-related gene expression, leading to neuronal death. Under physiological stress conditions, REST/NRSF over expression is known to activate neuronal survival in the brain. Alterations in REST/NRSF expression in the brain has been reported in stressed animal models and in the post-mortem brain of patients with depression. Here, we highlight the neuroprotective function of REST/NRSF and discuss dysregulation of REST/NRSF and neuronal damage during social stress and depression.
    Matched MeSH terms: Depression/metabolism*
  4. Fulltext Acupuncture Alleviates CUMS-Induced Depression-Like Behaviors by Restoring Prefrontal Cortex Neuroplasticity
    Li P, Huang W, Chen Y, Aslam MS, Cheng W, Huang Y, et al.
    Neural Plast, 2023;2023:1474841.
    PMID: 37179843 DOI: 10.1155/2023/1474841
    PURPOSE: To explore the therapeutic efficiency of acupuncture and the related molecular mechanism of neural plasticity in depression.

    METHODS: Chronic unpredictable mild stress- (CUMS-) induced rats were established for the depression animal model. There were a total of four rat groups, including the control group, the CUMS group, the CUMS+acupuncture group, and the CUMS+fluoxetine group. The acupuncture group and the fluoxetine group were given a 3-week treatment after the modeling intervention. The researcher performed the open-field, elevated plus maze, and sucrose preference tests to evaluate depressive behaviors. The number of nerve cells, dendrites' length, and the prefrontal cortex's spine density were detected using Golgi staining. The prefrontal cortex expression, such as BDNF, PSD95, SYN, and PKMZ protein, was detected using the western blot and RT-PCR.

    RESULTS: Acupuncture could alleviate depressive-like behaviors and promote the recovery of the neural plasticity functions in the prefrontal cortex, showing the increasing cell numbers, prolonging the length of the dendrites, and enhancing the spine density. The neural plasticity-related proteins in the prefrontal cortex, including BDNF, PSD95, SYN, and PKMZ, were all downregulated in the CUMS-induced group; however, these effects could be partly reversed after being treated by acupuncture and fluoxetine (P < 0.05).

    CONCLUSION: Acupuncture can ameliorate depressive-like behaviors by promoting the recovery of neural plasticity functions and neural plasticity-related protein upregulation in the prefrontal cortex of CUMS-induced depressed rats. Our study provides new insights into the antidepressant approach, and further studies are warranted to elucidate the mechanisms of acupuncture involved in depression treatment.

    Matched MeSH terms: Depression/metabolism
  5. Fulltext A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank
    Shen X, Howard DM, Adams MJ, Hill WD, Clarke TK, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, et al.
    Nat Commun, 2020 05 08;11(1):2301.
    PMID: 32385265 DOI: 10.1038/s41467-020-16022-0
    Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, pFDR 
    Matched MeSH terms: Depression/metabolism
  6. The effect of nitrazepam on depression and curiosity in behavioral tests in mice: The role of potassium channels
    Nikoui V, Ostadhadi S, Azhand P, Zolfaghari S, Amiri S, Foroohandeh M, et al.
    Eur J Pharmacol, 2016 Nov 15;791:369-376.
    PMID: 27615446 DOI: 10.1016/j.ejphar.2016.09.017
    Evidence show that gamma-aminobutyric acid (GABA) receptors are involved in depression, so the aim of this study was to investigate the effect of nitrazepam as agonist of GABAA receptors on depression and curiosity in male mice and the role of potassium channel in antidepressant-like response. For this purpose, we studied the antidepressant-like properties of fluoxetine, nitrazepam, glibenclamide, and cromakalim by both forced swimming test (FST) and tail suspension test (TST). Animals were injected by various doses of nitrazepam (0.05, 0.1, and 0.5mg/kg). Nitrazepam at dose of 0.5mg/kg significantly decreased the immobility time compared to control group in both FST and TST. Fluoxetine also showed such a response. Co-administration of nitrazepam (0.05mg/kg) with glibenclamide in TST (1mg/kg) and in FST (0.3, 1mg/kg) also showed antidepressant-like response. Beside, cromakalim (0.1mg/kg) could reverse the antidepressant-like effect of nitrazepam (0.5mg/kg) in both FST and TST, while cromakalim and glibenclamide alone could not change the immobility time compared to control group (P>0.05). The hole-board test revealed that nitrazepam at doses of 0.5 and 0.1mg/kg could increase the activity of the animal's head-dipping and boost the curiosity and exploration behavior of mice. The results of this study revealed that nitrazepam may possess antidepressant-like properties and this effect is dependent to potassium channels in both FST and TST.
    Matched MeSH terms: Depression/metabolism*
  7. Fulltext Acupuncture alleviates CUMS-induced depression-like behaviors of rats by regulating oxidative stress, neuroinflammation and ferroptosis
    Shen J, Hao C, Yuan S, Chen W, Tong T, Chen Y, et al.
    Brain Res, 2024 Mar 01;1826:148715.
    PMID: 38142722 DOI: 10.1016/j.brainres.2023.148715
    BACKGROUND: The treatment of depression with acupuncture has been documented. The mechanism behind acupuncture's curative and preventative effects is still unknown.

    METHODS: The current study examined the effects of acupuncture on depression-like behaviors in a rat model of chronic unpredictable mild stress (CUMS), while also exploring its potential mechanisms. A total of six groups of rats were randomly assigned: control, CUMS, acupuncture, fluoxetine, acupoint catgut embedding and sham acupoint catgut embedding. Fluoxetine (2.1 mg/kg) and acupoint catgut embedding were used for comparative research to acupuncture. The modelling evaluation is measured by body weight and behavior tests. Western blotting and reverse transcription-polymerase chain reaction were used to detect the proteins and mRNA expression of Silent information regulator 1 (Sirt1)/ nuclear factor-erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1)/ Glutathione peroxidase 4 (GPX4) pathway in the hippocampus. The expression of oxidative stress (OS)-related proteins and inflammatory cytokines in the serum was detected with ELISA. Immunofluorescence showed microglia and astrocytes activity in the hippocampus.

    RESULTS: Acupuncture and fluoxetine could alleviate CUMS-induced depression-like behaviors. Acupuncture was also found to effectively reverse the levels of MDA, SOD, GSH, GSH-PX and T-AOC, IL-1β, IL-6 and TNF-α in the serum of CUMS-induced rats. Rats with CUMS showed decreased levels of Sirt1, Nrf2, HO-1 and GPX4 in the hippocampus, while acupuncture treatment could partly reverse the diminished effects. In addition, acupuncture treatment significantly reduced the activation of hippocampal microglia and astrocytes in CUMS-induced rats.

    CONCLUSION: The study's findings indicate that acupuncture has the potential to mitigate depression-like behaviors in rats induced with CUMS by mitigating OS and reducing neuroinflammation.

    Matched MeSH terms: Depression/metabolism
  8. Fulltext Enhancement of BDNF concentration and restoration of the hypothalamic-pituitary-adrenal axis accompany reduced depressive-like behaviour in stressed ovariectomised rats treated with either Tualang honey or estrogen
    Al-Rahbi B, Zakaria R, Othman Z, Hassan A, Ahmad AH
    ScientificWorldJournal, 2014;2014:310821.
    PMID: 24550703 DOI: 10.1155/2014/310821
    A possible interaction between glucocorticoids and estrogen-induced increases in brain-derived-neurotrophic factor (BDNF) expression in enhancing depressive-like behaviour has been documented. Here we evaluated the effects of Tualang honey, a phytoestrogen, and 17 β -estradiol (E2) on the depressive-like behaviour, stress hormones, and BDNF concentration in stressed ovariectomised (OVX) rats. The animals were divided into six groups: (i) nonstressed sham-operated control, (ii) stressed sham-operated control, (iii) nonstressed OVX, (iv) stressed OVX, (v) stressed OVX treated with E2 (20  μg daily, sc), and (vi) stressed OVX treated with Tualang honey (0.2 g/kg body weight daily, orally). Two months after surgery, the animals were subjected to social instability stress procedure followed by forced swimming test. Struggling time, immobility time, and swimming time were scored. Serum adrenocorticotropic hormone (ACTH) and corticosterone levels, and the BDNF concentration were determined using commercially available ELISA kits. Stressed OVX rats displayed increased depressive-like behaviour with significantly increased serum ACTH and corticosterone levels, while the BDNF concentration was significantly decreased compared to other experimental groups. These changes were notably reversed by both E2 and Tualang honey. In conclusion, both Tualang honey and E2 mediate antidepressive-like effects in stressed OVX rats, possibly acting via restoration of hypothalamic-pituitary-adrenal axis and enhancement of the BDNF concentration.
    Matched MeSH terms: Depression/metabolism*
  9. Anxiolytic- and antidepressant-like activities of a methanolic extract of Morinda citrifolia Linn. (noni) fruit in mice: Involvement of benzodiazepine-GABAAergic, serotonergic and adrenergic systems
    Narasingam M, Vijeepallam K, Mohamed Z, Pandy V
    Biomed Pharmacother, 2017 Dec;96:944-952.
    PMID: 29217165 DOI: 10.1016/j.biopha.2017.11.148
    This study presents anxiolytic- and antidepressant-like effects of a methanolic extract of Morinda citrifolia Linn. (noni) fruit (MMC) in well-established mouse models of anxiety and depression. The administration of MMC (1 g/kg, p.o.) and diazepam (1 mg/kg, i.p.) significantly attenuated anxiety-like behaviour in mice by increasing the percentage of time spent and number of entries in the open arms in the elevated plus maze (EPM), and significantly enhanced the exploration in the light box in the light/dark test (LDT). The pre-treatment with flumazenil (6 mg/kg, i.p.) or bicuculline (3 mg/kg, i.p.) or WAY 100635 (1 mg/kg, i.p.) antagonized the anxiolytic-like effect elicited by MMC (1 g/kg, p.o.). These results suggest the possible involvement of benzodiazepine-GABAAergic and serotonergic mechanisms in the anxiolytic-like effect of noni fruit. Meanwhile, in the antidepressant study, the administration of MMC (0.5 and 0.75 g/kg, p.o.) and desipramine (30 mg/kg, i.p.) significantly reduced the duration of immobility in the tail suspension test (TST). Furthermore, pre-treatment of mice with 4-chloro-DL-phenylalanine methyl ester hydrochloride (PCPA; 100 mg/kg, i.p., an inhibitor of serotonin synthesis) for four consecutive days or a single dose of WAY 100635 (1 mg/kg, i.p., 5HT1A receptor antagonist) or α-methyl-DL-tyrosine (AMPT; 100 mg/kg, i.p., an inhibitor of noradrenaline synthesis) significantly reversed the anti-immobility effect of MMC (0.5 g/kg, p.o.) in TST by indicating the specific involvement of the serotonergic and noradrenergic systems in the antidepressant-like effect of noni fruit. Taken together, these findings suggest that MMC has both anxiolytic- and antidepressant-like activities to be resorted as a valuable alternative therapy for comorbid anxiety and depressive conditions.
    Matched MeSH terms: Depression/metabolism
  10. Fulltext Antidepressant-like effects of fish, krill oils and Vit B12 against exposure to stress environment in mice models: current status and pilot study
    Zadeh-Ardabili PM, Rad SK, Rad SK, Movafagh A
    Sci Rep, 2019 Dec 27;9(1):19953.
    PMID: 31882885 DOI: 10.1038/s41598-019-56360-8
    Oxidative stress has significant role in pathophysiology of any kind of depression through actions of free radicals, non-radical molecules, and unbalancing antioxidant systems in body. In the current study, antidepressant responses of fish oil (FO), Neptune krill oil (NKO), vitamin B12 (Vit B12), and also imipramine (IMP) as the reference were studied. Natural light was employed to induce stress in the animals followed by oral administration of the drugs for 14 days. The antidepressant effect was assessed by tail suspension test (TST) and forced swimming test (FST), antioxidant enzymes and oxidative stress markers were then measured in the brain tissue of the animals. The administration of FO and NKO could significantly reduce the immobility of the animals; while, increasing climbing and swimming time compared to the normal saline in CUS-control group in TST and FST, similarly to IMP but not with Vit B12. Vit B12 could not effect on SOD activity and H2O2 level, but, cause decrease of the malondialdihydric (MDA) level and CAT activity, as well as increased the GPx and GSH activities. The rest treatments led to decrease of MDA, H2O2 levels and CAT activity and increase of GPx, SOD, GSH activities.
    Matched MeSH terms: Depression/metabolism*
  11. Fulltext Involvement of monoaminergic system in the antidepressant-like effect of aqueous extract of Channa striatus in mice
    Saleem AM, Taufik Hidayat M, Jais AM, Fakurazi S, Moklas MA, Sulaiman MR, et al.
    Eur Rev Med Pharmacol Sci, 2013;17(15):2019-22.
    PMID: 23884821
    BACKGROUND: In our previous study, the aqueous extract of Channa striatus (family: Channidae) fillet (AECSF) showed an antidepressant-like effect in mice. However, the mechanism of the antidepressant-like effect is unknown.
    AIM: The objective of this study was to explore the involvement of monoamines in the antidepressant-like effect of AECSF in mice.
    MATERIALS AND METHODS: AECSF was prepared by steaming the fillets of C. striatus. The male ICR mice were pretreated with various monoaminergic antagonists viz., p-chlorophenylalanine (100 mg/kg, i.p.), prazosin (1 mg/kg, i.p.) and yohimbine (1 mg/kg, i.p.), SCH23390 (0.05 mg/kg, s.c.) and sulpiride (50 mg/kg, i.p.) followed by treatment with AECSF and tested in tail suspension test (TST). Two-way ANOVA with Tukey test were used at p < 0.05 for significance.
    RESULTS: The pretreatments with p-chlorophenylalanine, prazosin and yohimbine, but not with SCH23390 and sulpiride, were able to reverse the antidepressant-like effect of AECSF in TST.
    CONCLUSIONS: The antidepressant-like effect of AECSF may be mediated through the serotonergic and noradrenergic systems and not through the dopaminergic system.
    Matched MeSH terms: Depression/metabolism
  12. Alpha-asarone attenuates depression-like behavior in nicotine-withdrawn mice: Evidence for the modulation of hippocampal pCREB levels during nicotine-withdrawal
    Chellian R, Pandy V, Mohamed Z
    Eur J Pharmacol, 2018 Jan 05;818:10-16.
    PMID: 29042206 DOI: 10.1016/j.ejphar.2017.10.025
    In the present study, the effect α-asarone on nicotine withdrawal-induced depression-like behavior in mice was investigated. In this study, mice were exposed to drinking water or nicotine solution (10-200µg/ml) as a source of drinking for forty days. During this period, daily fluid consumption, food intake and body weight were recorded. The serum cotinine level was estimated before nicotine withdrawal. Naïve mice or nicotine-withdrawn mice were treated with α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) for eight consecutive days and the forced swim test (FST) or locomotor activity test was conducted. In addition, the effect of α-asarone or bupropion on the hippocampal pCREB, CREB and BDNF levels during nicotine-withdrawal were measured. Results indicated that α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment did not significantly alter the immobility time in the FST or spontaneous locomotor activity in naïve mice. However, the immobility time of nicotine-withdrawn mice was significantly attenuated with α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment in the FST. Besides, α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment significantly attenuated the hippocampal pCREB levels in nicotine-withdrawn mice. Overall, the present results indicate that α-asarone treatment attenuated the depression-like behavior through the modulation of hippocampal pCREB levels during nicotine-withdrawal in mice.
    Matched MeSH terms: Depression/metabolism
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