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1.
Phytother Res ; 37(5): 1850-1863, 2023 May.
Article in English | MEDLINE | ID: covidwho-20245354

ABSTRACT

Evidence exists suggesting the anti-depressive activities of geniposide (GP), a major compound in Gardenia jasminoides Ellis. Accordingly, the present study attempts to explore the anti-depressive mechanism of GP in chronic unpredictable mild stress (CUMS)-induced depression-like behaviors of mice. CUMS-induced mice were given GP daily and subjected to behavioral tests to observe the effect of GP on the depression-like behaviors. It was noted that GP administration reduced depression-like behaviors in CUMS mice. Transcriptome sequencing was conducted in three control and three CUMS mice. Differentially expressed circRNAs, lncRNAs and mRNAs were then screened by bioinformatics analyses. Intersection analysis of the transcriptome sequencing results with the bioinformatics analysis results was followed to identify the candidate targets. We found that Gata2 alleviated depression-like behaviors via the metabolism- and synapse-related pathways. Gata2 was a target of miR-25-3p, which had binding sites to circ_0008405 and Oip5os1. circ_0008405 and Oip5os1 competitively bound to miR-25-3p to release the expression of Gata2. GP administration ameliorated depression-like behaviors in CUMS mice through regulation of the circ_0008405/miR-25-3p/Gata2 and Oip5os1/miR-25-3p/Gata2 crosstalk networks. Taken together, GP may exert a potential antidepressant-like effect on CUMS mice, which is ascribed to regulation of the circ_0008405/miR-25-3p/Gata2 and Oip5os1/miR-25-3p/Gata2 crosstalk networks.


Subject(s)
Depressive Disorder , MicroRNAs , Mice , Animals , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Depressive Disorder/drug therapy , Depression/drug therapy , Depression/metabolism , MicroRNAs/metabolism , GATA2 Transcription Factor
2.
Psychoneuroendocrinology ; 143: 105847, 2022 09.
Article in English | MEDLINE | ID: covidwho-1907693

ABSTRACT

Determining pre-existing biological risk markers of incident depression and other mental health sequelae after exposure to a new stressor would help identify vulnerable individuals and mechanistic pathways. This study investigated primarily whether hair cortisol predicted elevated depressive symptoms in middle-aged and older adults during the COVID-19 pandemic, 6 years later. A secondary aim was to deduce whether any association differed by sex. METHODS: We studied 1025 adults aged 50 and older (75% female) as part of The Irish Longitudinal Study on Ageing. Hair cortisol samples were collected at 2014 (Wave 3) and depressive symptoms were assessed using the 8-item Center for Epidemiological Studies Depression Scale in 2014 (Wave 3), 2016 (Wave 4), 2018 (Wave 5) and again in 2020 as part of TILDA's COVID-19 Study. Hierarchical mixed effects logistic regression models were applied to investigate the association between cortisol levels and clinically significant depressive symptoms before and during the COVID-19 pandemic. RESULTS: In a full covariate adjusted model there was a significant interaction between cortisol and wave on depressive symptoms (χ2 = 8.5, p = .03). Cortisol was positively and significantly associated with elevated depressive symptoms during the COVID-19 Study (OR =1.3, 95% CI 1.11, 1.56, p = .003), and was associated with an increased likelihood of reporting clinically significant depressive symptoms during first year of the COVID-19 pandemic, when compared with before, OR = 1.4, 95% CI 1.05, 1.9, p = .015. There was no evidence of effect modification by sex. CONCLUSIONS: Higher hair cortisol, assessed 6 years previously, predicted clinically significant depressive symptoms among middle-aged and older adults during (but not before) the pandemic. Findings suggest a biological phenotype which denotes increased susceptibility to the negative impact of environmental stress on psychological health.


Subject(s)
COVID-19 , Hydrocortisone , Biomarkers , Depression/metabolism , Female , Hair/metabolism , Humans , Hydrocortisone/metabolism , Longitudinal Studies , Male , Pandemics
3.
Int J Mol Sci ; 23(4)2022 Feb 13.
Article in English | MEDLINE | ID: covidwho-1715398

ABSTRACT

The phenomenon of individual variability in susceptibility/resilience to stress and depression, in which the hippocampus plays a pivotal role, is attracting increasing attention. We investigated the potential role of hippocampal cyclooxygenase-2 (COX-2), which regulates plasticity, neuroimmune function, and stress responses that are all linked to this risk dichotomy. We used a four-week-long chronic mild stress (CMS) paradigm, in which mice could be stratified according to their susceptibility/resilience to anhedonia, a key feature of depression, to investigate hippocampal expression of COX-2, a marker of microglial activation Iba-1, and the proliferation marker Ki67. Rat exposure, social defeat, restraints, and tail suspension were used as stressors. We compared the effects of treatment with either the selective COX-2 inhibitor celecoxib (30 mg/kg/day) or citalopram (15 mg/kg/day). For the celecoxib and vehicle-treated mice, the Porsolt test was used. Anhedonic (susceptible) but not non-anhedonic (resilient) animals exhibited elevated COX-2 mRNA levels, increased numbers of COX-2 and Iba-1-positive cells in the dentate gyrus and the CA1 area, and decreased numbers of Ki67-positive cells in the subgranular zone of the hippocampus. Drug treatment decreased the percentage of anhedonic mice, normalized swimming activity, reduced behavioral despair, and improved conditioned fear memory. Hippocampal over-expression of COX-2 is associated with susceptibility to stress-induced anhedonia, and its pharmacological inhibition with celecoxib has antidepressant effects that are similar in size to those of citalopram.


Subject(s)
Anhedonia/physiology , Cyclooxygenase 2/metabolism , Hippocampus/metabolism , Stress, Psychological/metabolism , Anhedonia/drug effects , Animals , Antidepressive Agents/pharmacology , Celecoxib/pharmacology , Citalopram/pharmacology , Depression/drug therapy , Depression/metabolism , Hindlimb Suspension/physiology , Hippocampus/drug effects , Male , Mice , Mice, Inbred C57BL , Rats , Rats, Wistar , Selective Serotonin Reuptake Inhibitors/pharmacology , Stress, Psychological/drug therapy , Swimming/physiology
4.
Biomed Pharmacother ; 144: 112291, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1466070

ABSTRACT

BACKGROUND: Oxytocin (OXT), a neuropeptide involved in mammal reproductive and prosocial behaviors, has been reported to interact with various stressor-provoked neurobiological changes, including neuroendocrine, neurotransmitter, and inflammatory processes. In view of disturbances in psychosocial relationships due to social isolation and physical distancing measures amid the COVID-19 pandemic, being one of the triggering factors for the recent rise in depression and anxiety, OXT is a potential candidate for a new antidepressant. METHODS: In this present study, we have aimed to investigate the effects of oral administration of Rosmarinus officinalis extract (RE), extracted from distillation residue of rosemary essential oil, on central OXT level in the context of other stress biomarkers and neurotransmitter levels in mice models. Tail suspension test (TST) and elevated plus maze test (EPMT) following LPS injection were employed to assess depressive- and anxiety-like behavior in mice, respectively. FINDINGS: Pretreatment with RE for seven days significantly improved behavior in TST and EPMT. Whole-genome microarray analysis reveals that RE significantly reversed TST stress-induced alterations in gene expressions related to oxytocinergic and neurotransmitter pathways and inflammatory processes. In both models, RE significantly increased central Oxt and Oxtr expressions, as well as OXT protein levels. RE also significantly attenuated stress-induced changes in serum corticosterone, brain and serum BDNF levels, and brain neurotransmitters levels in both models. INTERPRETATION: Altogether, our study is the first to report antidepressant- and anxiolytic-like activities of RE through modulating oxytocinergic system in mice brain and thus highlights the prospects of RE in the treatment of depressive disorders of psychosocial nature.


Subject(s)
Anti-Anxiety Agents/therapeutic use , Antidepressive Agents/therapeutic use , Oxytocin/metabolism , Plant Extracts/therapeutic use , Receptors, Oxytocin/metabolism , Rosmarinus , Animals , Anti-Anxiety Agents/isolation & purification , Anti-Anxiety Agents/pharmacology , Antidepressive Agents/isolation & purification , Antidepressive Agents/pharmacology , Anxiety/drug therapy , Anxiety/metabolism , Brain/drug effects , Brain/metabolism , Depression/drug therapy , Depression/metabolism , Dose-Response Relationship, Drug , Inflammation Mediators/antagonists & inhibitors , Inflammation Mediators/metabolism , Male , Mice , Mice, Inbred ICR , Oxytocin/agonists , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Receptors, Oxytocin/agonists
5.
Immunopharmacol Immunotoxicol ; 43(3): 309-318, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1242073

ABSTRACT

BACKGROUND: Depression affects people feeling to be anxious, worried, and restless. They also lose interest in activities, concentrating and appetite, they finally may attempt suicide. Depression is the second chronic disease, as a source of the global burden of disease, after heart disease. Its prevalence elevated seven times during the COVID-19. AIM: The current study was designed to evaluate camphor neuroprotective role against rats' ciprofloxacin-induced depression. MATERIALS AND METHODS: Depression was induced by administration of ciprofloxacin (50 mg/kg; orally) for 21 days. Wister albino male rats were divided into five groups. Group I (normal control): rats were given normal saline. Group II: rats received camphor (10 mg/kg; i.p.) for 21 days. Group III (depression control): rats received ciprofloxacin only. Groups IV and V: rats received camphor (5 and 10 mg/kg; i.p.) for 21 days concurrent with ciprofloxacin. Behavior tests as forced swimming test, activity cage, and rotarod were estimated. Oxidative stress and antioxidant biomarkers as malondialdehyde (MDA), nitric oxide (NO), catalase, and nuclear factor erythroid 2-related factor 2 (Nrf-2) besides inflammatory biomarkers as Toll-like receptor 4 (TLR4) and tumor necrosis factor alpha (TNF-α) as well as neurotransmitters were determined. Finally, histopathological examination was done. RESULTS: Camphor increased catalase and Nrf-2 activities, decreased NO, MDA, TNF-α, TLR4 serum levels, and elevating brain contents of serotonin, dopamine, gamma-amino butyric acid (GABA) and P190-RHO GTP protein with normal neuronal cells of the frontal cortex. CONCLUSION: Camphor has neuroprotective effect via modulation of Nrf-2 and TLR4 against ciprofloxacin-induced depression in rats.


Subject(s)
Camphor/pharmacology , Ciprofloxacin/adverse effects , Depression , NF-E2-Related Factor 2/metabolism , Neuroprotective Agents/pharmacology , Toll-Like Receptor 4/metabolism , Animals , COVID-19/metabolism , COVID-19/pathology , Ciprofloxacin/pharmacology , Depression/chemically induced , Depression/drug therapy , Depression/metabolism , Male , Rats , Rats, Wistar , SARS-CoV-2/metabolism , COVID-19 Drug Treatment
6.
Pharmacopsychiatry ; 54(5): 215-223, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1217715

ABSTRACT

INTRODUCTION: Depression is responsible for 800 000 deaths worldwide, a number that will rise significantly due to the COVID-19 pandemic. Affordable novel drugs with less severe side effects are urgently required. We investigated the effect of withanone (WN) from Withania somnifera on the serotonin system of wild-type and knockout Caenorhabditis elegans strains using in silico, in vitro, and in vivo methods. METHODS: WN or fluoxetine (as positive control drug) was administered to wild-type (N2) and knockout C. elegans strains (AQ866, DA1814, DA2100, DA2109, and MT9772) to determine their effect on oxidative stress (Trolox, H2DCFDA, and juglone assays) on osmotic stress and heat stress and lifespan. Quantitative real-time RT-PCR was applied to investigate the effect of WN or fluoxetine on the expression of serotonin receptors (ser-1, ser-4, ser-7) and serotonin transporter (mod-5). The binding affinity of WN to serotonin receptors and transporter was analyzed in silico using AutoDock 4.2.6. RESULTS: WN scavenged ROS in wild-type and knockout C. elegans and prolonged their lifespan. WN upregulated the expression of serotonin receptor and transporter genes. In silico analyses revealed high binding affinities of WN to Ser-1, Ser-4, Ser-7, and Mod-5. LIMITATIONS: Further studies are needed to prove whether the results from C. elegans are transferrable to mammals and human beings. CONCLUSION: WN ameliorated depressive-associated stress symptoms by activating the serotonin system. WN may serve as potential candidate in developing new drugs to treat depression.


Subject(s)
Depression , Receptors, Serotonin/metabolism , Serotonin Plasma Membrane Transport Proteins/metabolism , Synaptic Transmission/drug effects , Withanolides/pharmacology , Animals , Animals, Genetically Modified , Antidepressive Agents/pharmacology , COVID-19/psychology , Caenorhabditis elegans , Depression/drug therapy , Depression/metabolism , Fluoxetine/pharmacology , Humans , Longevity/drug effects , Oxidative Stress/drug effects , SARS-CoV-2
7.
Curr Opin Lipidol ; 32(3): 167-174, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1189521

ABSTRACT

PURPOSE OF REVIEW: The purpose of this review is to outline the relationship between cardiovascular disease (CVD) and depression, both as a cause of and a result of CVD. RECENT FINDINGS: The prevalence of depression seems to be increasing in the general population.It is likely that depression will be even more of a problem for CVD patients in the post-COVID-19 pandemic era.New studies confirm the independent association of depression with later incident CVD, although perhaps not as strong as suggested by some previous studies.Depression seems to be becoming even more prevalent in CVD patients, with new data for stroke and peripheral arterial disease patients.Cardiologists rarely screen for depression and most do not believe that they have a responsibility for detecting or treating depression.There are new data suggesting that patients who are more in control of their lives have better outcomes and that change is possible. SUMMARY: Depression is preventable and treatable. It is imperative to detect and manage depression in CVD patients. Additional research is required to see whether or not comprehensive patient screening for depression translates into both better quality of life and improved clinical outcomes.


Subject(s)
Cardiovascular Diseases/complications , Depression/complications , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/physiopathology , Depression/metabolism , Depression/physiopathology , Disabled Persons , Humans , Lipid Metabolism , Prevalence
8.
Mol Psychiatry ; 26(9): 5087-5096, 2021 09.
Article in English | MEDLINE | ID: covidwho-1065838

ABSTRACT

The fine-tuning of neuroinflammation is crucial for brain homeostasis as well as its immune response. The transcription factor, nuclear factor-κ-B (NFκB) is a key inflammatory player that is antagonized via anti-inflammatory actions exerted by the glucocorticoid receptor (GR). However, technical limitations have restricted our understanding of how GR is involved in the dynamics of NFκB in vivo. In this study, we used an improved lentiviral-based reporter to elucidate the time course of NFκB and GR activities during behavioral changes from sickness to depression induced by a systemic lipopolysaccharide challenge. The trajectory of NFκB activity established a behavioral basis for the NFκB signal transition involved in three phases, sickness-early-phase, normal-middle-phase, and depressive-like-late-phase. The temporal shift in brain GR activity was differentially involved in the transition of NFκB signals during the normal and depressive-like phases. The middle-phase GR effectively inhibited NFκB in a glucocorticoid-dependent manner, but the late-phase GR had no inhibitory action. Furthermore, we revealed the cryptic role of basal GR activity in the early NFκB signal transition, as evidenced by the fact that blocking GR activity with RU486 led to early depressive-like episodes through the emergence of the brain NFκB activity. These results highlight the inhibitory action of GR on NFκB by the basal and activated hypothalamic-pituitary-adrenal (HPA)-axis during body-to-brain inflammatory spread, providing clues about molecular mechanisms underlying systemic inflammation caused by such as COVID-19 infection, leading to depression.


Subject(s)
Depression/metabolism , NF-kappa B , Receptors, Glucocorticoid , Animals , Brain/metabolism , Hypothalamo-Hypophyseal System/metabolism , Mice , NF-kappa B/metabolism , Pituitary-Adrenal System/metabolism , Receptors, Glucocorticoid/metabolism
9.
PLoS One ; 16(1): e0245190, 2021.
Article in English | MEDLINE | ID: covidwho-1021677

ABSTRACT

Social isolation has affected a large number of people and may lead to impairment of physical and mental health. Although stress resulting from social isolation may increase cancer progression, its interference on tumorigenesis is poorly known. In this study, we used a preclinical model to evaluate the effects of social isolation stress on chemically induced oral carcinogenesis. Sixty-two 21-day-old male Wistar rats were divided into isolated and grouped groups. After 90 days of age, the rats from both groups underwent oral carcinogenesis with 4-nitroquinoline 1-oxide (4NQO) for 20 weeks. All rats were assessed for depressive-like behavior and euthanized for oral squamous cell carcinoma (OSCC) diagnosis and measurement of inflammatory mediators in the tumor microenvironment. Social isolation stress increased the OSCC occurrence by 20.4% when compared to control. Isolated rats also showed higher tumor volume and cachexia than the grouped rats. Social isolation did not induce changes in the depressive-like behavior after carcinogenic induction. Tumors from stressed rats had increased levels of the inflammatory mediators, TNF-alpha, IL1-beta and MCP-1. The concentrations of TNF-alpha and MCP-1 were significantly increased in the large tumors from isolated animals. Higher tumor levels of TNF-alpha, IL-6, IL1-beta and MCP-1 were positively correlated with OSCC growth. This study provides the first evidence that social isolation stress may facilitate OSCC occurrence and tumor progression, an event accompanied by increased local levels of inflammatory mediators.


Subject(s)
4-Nitroquinoline-1-oxide/toxicity , Behavior, Animal , Depression , Head and Neck Neoplasms , Social Isolation , Squamous Cell Carcinoma of Head and Neck , Stress, Psychological , Animals , Cytokines/metabolism , Depression/metabolism , Depression/pathology , Depression/physiopathology , Head and Neck Neoplasms/chemically induced , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/physiopathology , Inflammation Mediators/metabolism , Male , Neoplasm Proteins/metabolism , Rats , Rats, Wistar , Squamous Cell Carcinoma of Head and Neck/chemically induced , Squamous Cell Carcinoma of Head and Neck/metabolism , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/physiopathology , Stress, Psychological/metabolism , Stress, Psychological/pathology , Stress, Psychological/physiopathology
10.
Prostaglandins Leukot Essent Fatty Acids ; 161: 102177, 2020 10.
Article in English | MEDLINE | ID: covidwho-796199

ABSTRACT

As the infected cases of COVID-19 reach more than 20 million with more than 778,000 deaths globally, an increase in psychiatric disorders including anxiety and depression has been reported. Scientists globally have been searching for novel therapies and vaccines to fight against COVID-19. Improving innate immunity has been suggested to block progression of COVID-19 at early stages, while omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to have immunomodulation effects. Moreover, n-3 PUFAs have also been shown to improve mood disorders, thus, future research is warranted to test if n-3 PUFAs may have the potential to improve our immunity to counteract both physical and mental impact of COVID-19.


Subject(s)
Anxiety/prevention & control , Coronavirus Infections/prevention & control , Depression/prevention & control , Dietary Supplements , Fatty Acids, Omega-3/administration & dosage , Immunologic Factors/administration & dosage , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Anxiety/immunology , Anxiety/metabolism , Anxiety/virology , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Cytokines/biosynthesis , Cytokines/immunology , Dendritic Cells/drug effects , Dendritic Cells/immunology , Dendritic Cells/virology , Depression/immunology , Depression/metabolism , Depression/virology , Epithelial Cells/drug effects , Epithelial Cells/immunology , Epithelial Cells/virology , Fatty Acids, Omega-3/immunology , Fatty Acids, Omega-3/metabolism , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/immunology , Humans , Immunity, Innate/drug effects , Immunologic Factors/immunology , Immunologic Factors/metabolism , Lymphocytes/drug effects , Lymphocytes/immunology , Lymphocytes/virology , Macrophages/drug effects , Macrophages/immunology , Macrophages/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , SARS-CoV-2
11.
Psychiatry Res ; 291: 113198, 2020 09.
Article in English | MEDLINE | ID: covidwho-548196

ABSTRACT

An option currently being explored for the treatment of COVID-19 is the use of interferons (INFs), either alone or in combination with other antiviral agents. INFs are known to shift the metabolism of tryptophan (TRP) away from its role as a precursor of serotonin. For some patients, reduction in TRP levels may either expose an underlying vulnerability to depression or trigger a de novo episode of depression. This Commentary discusses the pathway involved and recommends in-hospital augmentation with foods or supplements that increase TRP levels for COVID-19 patients treated with INFs. Selective serotonin reuptake inhibitors may also be tried if the depressive symptomatology is not short-lived.


Subject(s)
Betacoronavirus , Coronavirus Infections/metabolism , Coronavirus Infections/psychology , Depression/metabolism , Interferons/metabolism , Pneumonia, Viral/metabolism , Pneumonia, Viral/psychology , COVID-19 , Depression/psychology , Humans , Pandemics , SARS-CoV-2 , Serotonin/metabolism , Tryptophan/metabolism
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