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1.
Adv Exp Med Biol ; 1264: 67-80, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33332004

RESUMO

There is a growing body of evidence pointing to the co-occurrence of cannabis use and depression. There is also some evidence that the use of cannabis may lead to the onset of depression; however, strong evidence points to the inverse association; i.e. that depression may lead to the onset or increase in cannabis use frequency. Observational and epidemiological studies have not indicated a positive long-term effect of cannabis use on the course and outcome of depression. The association between cannabis use and depression may be stronger among men during adolescence and emerging adulthood and stronger in women during midlife. There is an indication for potential genetic correlation contributing to the comorbidity of cannabis dependence and major depression, namely that serotonin (5-HT) may mediate such association and there is also evidence for specific risk alleles for cannabis addiction. There is preclinical evidence that alteration in the endocannabinoid system could potentially benefit patients suffering from depression. However, the issue of using cannabis as an anti-depressant is at an early stage of examination and there is little evidence to support it. Finally, there has been little support to the notion that selective serotonin reuptake inhibitors (SSRIs) may be effective in decreasing depressive symptoms or rates of substance use in adolescents treated for depression and a co-occurring substance use disorder. In conclusion, despite methodological limitations, research in the past decades has broadened our knowledge on the association between cannabis use and depression from epidemiological, neurological, genetic, and pharmacological perspectives.


Assuntos
Cannabis/efeitos adversos , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Transtorno Depressivo Maior/induzido quimicamente , Transtorno Depressivo Maior/tratamento farmacológico , Comorbidade , Depressão/epidemiologia , Depressão/genética , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/genética , Humanos , Abuso de Maconha/epidemiologia
2.
Rev Saude Publica ; 54: 133, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33331527

RESUMO

OBJECTIVE: To explore the association of occupational pesticide exposure with acute and mental health symptoms. METHODS: Cross-sectional survey carried out with 78 Brazilian family farmers, who were pesticide applicators and helpers conveniently selected. Symptoms and exposure data were collected by interviews, and mental health outcomes by the Self-Reporting Questionnaire. Blood samples were analyzed to assess cholinesterase levels. Exposure indicators and symptoms were compared between applicators and helpers, and Poisson regression was performed to estimate prevalence ratios. RESULTS: Farmers reported exposure to multiple pesticides from early ages; they worked without safety training, technical support, and full protective equipment, and they had a high prevalence of acute and mental health symptoms (e.g., headache, mucosal irritation, tachycardia, and depressive signs). Applicators had more cholinesterase changes than helpers, but less symptoms. Helpers used less personal protection and had significantly higher prevalence ratio of headache, dyspnea, wheezing, cough, poor digestion, tiredness, and feeling worthless, after adjustment. CONCLUSIONS: Acute and mental health symptoms were observed, both among farmers and helpers. Thus, surveillance actions must be reinforced in Brazil, technical support and safety training improved, focused on applicators and helpers, who are occupationally and environmentally exposed to pesticides. Agricultural practices of these groups with less pesticide use should receive incentive.


Assuntos
Depressão/induzido quimicamente , Fazendeiros , Cefaleia/induzido quimicamente , Exposição Ocupacional/estatística & dados numéricos , Praguicidas/envenenamento , Praguicidas/toxicidade , Envenenamento/epidemiologia , Doenças Respiratórias/induzido quimicamente , Taquicardia/induzido quimicamente , Adolescente , Adulto , Agricultura , Brasil/epidemiologia , Criança , Estudos Transversais , Depressão/epidemiologia , Família , Feminino , Cefaleia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Prevalência , Doenças Respiratórias/diagnóstico , Doenças Respiratórias/epidemiologia , Taquicardia/epidemiologia , Adulto Jovem
3.
Nutrients ; 12(12)2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33322645

RESUMO

Neuroinflammation is associated with an increased risk of depression. Lipopolysaccharide (LPS) treatment is known to induce pro-inflammatory cytokine secretion and a depressive-like phenotype in mice. Although Erythronium japonicum exhibits various health benefits, the role of E. japonicum extract (EJE) in inflammation-associated depression is unknown. This study aimed to explore the anti-inflammatory effect of EJE on LPS-induced depressive symptoms in mice using the open field test (OFT), passive avoidance test (PAT), tail suspension test (TST), and forced swim test (FST). LPS-treated mice had significantly increased immobility time in the TST and FST, decreased step-through latency time in the PAT, and decreased locomotor activity in the OFT. However, administration of 100 and 300 mg/kg of EJE significantly improved these depressive-like behaviors. EJE also prevented the increase in mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, and monocyte chemoattractant protein-1 (MCP-1), and the decrease in IL-10 levels by inhibiting nuclear factor-κB (NF-κB) subunit p65 phosphorylation. Additionally, LPS-treated mice showed markedly decreased brain-derived neurotrophic factor (BDNF) levels and phosphorylation of phosphoinositide 3-kinase (PI3K) and Akt, while EJE treatment significantly increased these levels in the hippocampus. These results suggest that EJE ameliorated LPS-induced depressive-like behavior by reducing LPS-induced neuroinflammation and activating the BDNF-PI3K/Akt pathway.


Assuntos
Anti-Inflamatórios/farmacologia , Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Liliaceae , Extratos Vegetais/farmacologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/induzido quimicamente , Modelos Animais de Doenças , Elevação dos Membros Posteriores , Lipopolissacarídeos , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Natação
4.
Artigo em Inglês | MEDLINE | ID: mdl-33327373

RESUMO

Depression is a risk factor for nicotine use and withdrawal. Population level epidemiologic studies that include users of either combustible or electronic cigarette (NICUSER) could inform interventions to reduce nicotine dependence in vulnerable populations. The current study examined the relationship between depression diagnosis (DEPDX), NICUSER, and lifetime rates of DSM-V nicotine withdrawal (NW) symptoms in a nationally representative sample of US adults (N = 979), who answered related questions in surveys administered through GfK's KnowledgePanel. Over 42% of the sample reported lifetime ever combustible cigarette use, 15.6% electronic-cigarette use, and 45.9% either (NICUSER). Weighted logistic regression analyses (controlling for age and gender) found that DEPDX was associated with 2.3 times increased odds (ratio (OR); 95% Confidence Interval (CI): 1.5-3.5) of being a NICUSER. Regarding risks of NW symptoms among NICUSER, models that additionally controlled for frequency of nicotine use found that DEPDX was significantly associated with increased odds of concentration problems (OR = 2.4; 95% CI: 1.3-4.5) and depressed mood (OR = 2.2; 95% CI: 1.1-4.1) when quitting or cutting down on nicotine use. Results highlight the consistent comorbidity between depression, nicotine use, and symptomatic nicotine withdrawal in a population-based sample of combustible and electronic cigarette users.


Assuntos
Fumar Cigarros , Depressão , Nicotina , Síndrome de Abstinência a Substâncias , Vaping , Adulto , Fumar Cigarros/efeitos adversos , Fumar Cigarros/epidemiologia , Estudos Transversais , Depressão/induzido quimicamente , Depressão/epidemiologia , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nicotina/efeitos adversos , Síndrome de Abstinência a Substâncias/epidemiologia , Vaping/efeitos adversos
5.
Psychopharmacology (Berl) ; 237(8): 2531-2545, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32488348

RESUMO

AIM: Indoleamine 2,3-dioxygenase 1 (IDO) is responsible for the progression of the kynurenine pathway, which has been implicated in the pathophysiology of inflammation-induced depression. It has been reported that asperosaponin VI (ASA VI) could play a neuroprotective role through anti-inflammatory and antioxidant. In this study, we examined the antidepressant effect of ASA VI in lipopolysaccharide (LPS)-treated mice and further explored its molecular mechanism by looking into the microglial kynurenine pathway. METHODS: To generate the model, LPS (0.83 mg/kg) was administered intraperitoneally to mice. The mice received ASA VI (10 mg/kg, 20 mg/kg, 40 mg/kg, and 80 mg/kg, i.p.) 30 min before LPS injection. Depressive-like behaviors were evaluated based on the duration of immobility in the forced swim test. Microglial activation and inflammatory cytokines were detected by immunohistochemistry, real-time PCR, and ELISA. The TLR4/NF-κB signaling pathway and the expression of IDO, GluA2, and CamKIIß were also measured by western blotting. RESULTS: ASA VI exhibited significant antidepressant activity in the presence of LPS on immobility and latency times in the forced swim test. The LPS-induced activation of microglia and inflammatory response were inhibited by ASA VI, which showed a dose-dependent pattern. TLR4/NF-κB signaling pathway also was suppressed by ASA VI in the hippocampus and prefrontal cortex of LPS-treated mice. Furthermore, ASA VI inhibited the increase in IDO protein expression and normalized the aberrant glutamate transmission in the hippocampus and prefrontal cortex caused by LPS administration. CONCLUSION: Our results propose a promising antidepressant effect for ASA VI possibly through the downregulation of IDO expression and normalization of the aberrant glutamate transmission. This remedying effect of ASA VI could be attributed to suppress microglia-mediated neuroinflammatory response via inhibiting the TLR4/NF-κB signaling pathway.


Assuntos
Antidepressivos/farmacologia , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Microglia/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Saponinas/farmacologia , Receptor 4 Toll-Like/antagonistas & inibidores , Animais , Anti-Inflamatórios/farmacologia , Antidepressivos/uso terapêutico , Células Cultivadas , Depressão/induzido quimicamente , Depressão/metabolismo , Depressão/psicologia , Expressão Gênica , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/biossíntese , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , NF-kappa B/metabolismo , Saponinas/uso terapêutico , Receptor 4 Toll-Like/metabolismo
6.
Environ Res ; 188: 109760, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32534257

RESUMO

BACKGROUND: The effect of household pesticide exposure on depressive symptoms in the general population is underexplored, and the role of exercise in the association between pesticide exposure and depressive symptoms is unclear. OBJECTIVE: The goals of this study are to examine whether the associations between household pesticide exposure and depressive symptoms exist in the general population, and whether exercise can attenuate these associations. METHODS: We used data from the 2005-2014 National Health and Nutrition Examination Surveys (NHANES), including a total of 14708 US adult participants who were 20 years or older. Depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9). Exercise information on the recreational physical activity (RPA) and pesticide exposure were self-reported in an interview. RESULTS: Participants with exposure of household pesticide had a higher odds ratio ([OR]; OR = 1.32, 95% confidence intervals [CI]: 1.12-1.56) for depressive symptoms, compared to those who had not been unexposed. A significant interaction between exercise and pesticide exposure on depressive symptoms was observed (P = 0.038). Stratified analysis showed that household pesticide exposure was associated with a 50% higher risk of depressive symptoms (OR = 1.50, 95% CI: 1.20-1.86) in the population with light RPA. However, we did not find a significant association in the group with moderate + vigorous RPA (P = 0.305). CONCLUSION: This study further confirms that household pesticide exposure is associated with an elevated risk of depressive symptoms in the general population. More importantly, we for the first time reports that moderate + vigorous RPA attenuates the positive association between household pesticide exposure and depressive symptoms.


Assuntos
Inquéritos Nutricionais , Praguicidas , Adulto , Depressão/induzido quimicamente , Depressão/epidemiologia , Exercício Físico , Humanos , Razão de Chances , Praguicidas/toxicidade , Autorrelato
7.
Psychopharmacology (Berl) ; 237(8): 2517-2530, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32445053

RESUMO

RATIONALE: Major depression is a serious, but common, psychological disorder, which consists of a long-lasting depressive mood, feelings of helplessness, anhedonia, and sleep disturbances. It has been reported that rats with bilateral olfactory bulbectomies (OBXs) exhibit depressive-like behaviors which indicates that the olfactory bulb (OB) plays an important role in the formation of depression. However, which type of OB neurons plays an important role in the formation of depression remains unclear. OBJECTIVE: To determine the role of OB neuronal types in depression and related sleep-wake dysfunction. METHODS: Firstly, we established and evaluated a conventional physical bilateral OBX depression model. Secondly, we used chemical methods to ablate OB neurons, while maintaining the original shape, and evaluated depressive-like behaviors. Thirdly, we utilized AAV-flex-taCasp3-TEVp and transgenetic mice to specifically ablate the OB GABAergic or glutamatergic neurons, then evaluated depressive-like behaviors. RESULTS: Compared with measured parameters in sham mice, mice with OBXs or ibotenic acid-induced OB lesions exhibited depressive-like behaviors and sleep disturbances, as demonstrated by results of depressive-like behavior tests and sleep recordings. Selective lesioning of OB glutamatergic neurons, but not GABAergic neurons induced depressive-like behaviors and increased rapid eye movement sleep during the light phase of the circadian cycle. CONCLUSIONS: These results indicate that OB glutamatergic neurons play a key role in olfactory-related depression and sleep disturbance.


Assuntos
Depressão/metabolismo , Ácido Glutâmico/metabolismo , Neurônios/metabolismo , Bulbo Olfatório/metabolismo , Bulbo Olfatório/cirurgia , Transtornos do Sono-Vigília/metabolismo , Técnicas de Ablação/métodos , Animais , Depressão/induzido quimicamente , Depressão/psicologia , Agonistas de Aminoácidos Excitatórios/toxicidade , Ácido Ibotênico/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Distribuição Aleatória , Sono/efeitos dos fármacos , Sono/fisiologia , Transtornos do Sono-Vigília/induzido quimicamente
8.
J Urol ; 204(4): 793-798, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32294395

RESUMO

PURPOSE: Depressed mood and suicidality reported with 5α-reductase inhibitors (finasteride and dutasteride) during post-marketing surveillance resulted in the addition of depression risk to finasteride labeling. As peer reviewed studies are limited and have reported mixed findings, we further evaluated 5α-reductase inhibitor exposure and depression risk using sequence symmetry analysis. MATERIALS AND METHODS: National Veterans Health Administration administrative data were used to identify 53,848 male patients initiating 5α-reductase inhibitor therapy during fiscal year 2014. Incident depression events were assessed separately using the 2 measures of antidepressant prescription and depression diagnosis. Symmetry ratios were calculated as the ratio of patients with an incident depression event in the year following 5α-reductase inhibitor initiation to the year preceding initiation. An identical exposure counterfactual analysis was conducted among veterans initiating α1-adrenergic receptor antagonists. RESULTS: Incident antidepressant prescribing was observed in 2,563 patients following 5α-reductase inhibitor initiation and 3,051 patients preceding 5α-reductase inhibitor initiation (SR 0.84, 95% CI 0.80-0.89). Similar findings were observed for incident depression diagnosis (SR 0.83, 95% CI 0.79-0.86). Stratification by age group, 5α-reductase inhibitor agent, antidepressant class, prior α1-adrenergic receptor antagonist exposure and depression diagnosis type failed to demonstrate any positive association between 5α-reductase inhibitor and depression. Nearly identical results were observed in the α1-adrenergic receptor antagonist analysis (SR 0.87, 95% CI 0.84-0.90). CONCLUSIONS: Initiation of a 5α-reductase inhibitor was not associated with increased risk of depression. Our findings support the hypothesis that depression is more likely attributable to underlying benign prostatic hyperplasia and associated lower urinary tract symptoms than 5α-reductase inhibitor exposure.


Assuntos
Inibidores de 5-alfa Redutase/efeitos adversos , Depressão/induzido quimicamente , Depressão/epidemiologia , Dutasterida/efeitos adversos , Finasterida/efeitos adversos , Hiperplasia Prostática/tratamento farmacológico , Inibidores de 5-alfa Redutase/uso terapêutico , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
Am J Chin Med ; 48(3): 559-577, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32345030

RESUMO

Depression is partially caused by inflammation in the central nervous system. Early study demonstrated that musk, glandular secretion from male musk deer, exerted an antidepressant-like effect. The aim of this study was to investigate if muscone, a bioactive ingredient in musk, could ameliorate neuroinflammation and depressive-like behaviors as well as explore the potential action mechanism. Mice were intraperitoneally (i.p.) injected with muscone for 2 weeks prior to administration of lipopolysaccharides (LPS, 1mg/kg, i.p.). Pre-treatment with muscone reversed the LPS-induced decrease in body weight within 24h and ameliorated depressive-like behaviors shown by sucrose preference, tail suspension test, and forced swimming test. LPS-induced activation of microglial cells and elevation in expression of inflammatory cytokines including IL-1ß, RANTES, and MCP-1 in the prefrontal cortex of mice were effectively abrogated by muscone, which significantly down-regulated expression of TLR4, MyD88, Caspase-1, NLRP3, renin, and Ang II. In addition, treatment of BV2 microglia cells with muscone markedly attenuated the LPS-induced rise in protein expression of TLR4, Ang II, and IL-1ß. This study revealed that muscone could ameliorate LPS-induced depressive-like behaviors by repressing neuroinflammation in the prefrontal cortex of mice caused by its suppression on microglia activation and production of inflammatory cytokines via acting on TLR4 pathway and RAS cascade.


Assuntos
Cicloparafinas/administração & dosagem , Cicloparafinas/farmacologia , Depressão/tratamento farmacológico , Lipopolissacarídeos/efeitos adversos , Animais , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Cervos , Depressão/induzido quimicamente , Mediadores da Inflamação/metabolismo , Injeções Intraperitoneais , Masculino , Camundongos , Microglia/citologia , Microglia/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo
10.
Radiat Res ; 193(5): 407-424, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32134362

RESUMO

Radiotherapy, surgery and the chemotherapeutic agent temozolomide (TMZ) are frontline treatments for glioblastoma multiforme (GBM). However beneficial, GBM treatments nevertheless cause anxiety or depression in nearly 50% of patients. To further understand the basis of these neurological complications, we investigated the effects of combined radiotherapy and TMZ chemotherapy (combined treatment) on neurological impairments using a mouse model. Five weeks after combined treatment, mice displayed anxiety-like behaviors, and at 15 weeks both anxiety- and depression-like behaviors were observed. Relevant to the known roles of the serotonin axis in mood disorders, we found that 5HT1A serotonin receptor levels were decreased by ∼50% in the hippocampus at both early and late time points, and a 37% decrease in serotonin levels was observed at 15 weeks postirradiation. Furthermore, chronic treatment with the selective serotonin reuptake inhibitor fluoxetine was sufficient for reversing combined treatment-induced depression-like behaviors. Combined treatment also elicited a transient early increase in activated microglia in the hippocampus, suggesting therapy-induced neuroinflammation that subsided by 15 weeks. Together, the results of this study suggest that interventions targeting the serotonin axis may help ameliorate certain neurological side effects associated with the clinical management of GBM to improve the overall quality of life for cancer patients.


Assuntos
Neurologia , Radioterapia/efeitos adversos , Temozolomida/efeitos adversos , Animais , Ansiedade/diagnóstico , Ansiedade/etiologia , Ansiedade/metabolismo , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/efeitos da radiação , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/patologia , Região CA1 Hipocampal/efeitos da radiação , Terapia Combinada/efeitos adversos , Depressão/induzido quimicamente , Depressão/etiologia , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Masculino , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Neurônios/efeitos da radiação , Receptor 5-HT1A de Serotonina/metabolismo , Serotonina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Temozolomida/uso terapêutico
11.
Int J Mol Sci ; 21(4)2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32098023

RESUMO

In the pathology-oriented study of depression, inflammation hypothesis has received increasing attention for recent years. To mimic the depressive state caused by inflammation, rodents injected intraperitoneally with lipopolysaccharide (LPS) are usually used to stimulate an immune response. However, the dose of LPS that causes depressive-like behavior varies widely across many literatures. Previous study has uncovered the non-linearity in the dose-effect relationship for the depressive-like behavior induced by LPS administration, while the reason for this is still unclear. The present study aims to investigate the underlying mechanisms of this non-linear dose-dependent relationship. Four groups of mice were injected intraperitoneally with different doses of LPS (0, 0.32, 0.8, and 2 mg/kg). The tail suspension test was conducted to evaluate the depressive-like behavior within 23-25 h after the LPS administration. The neuroplasticity was assessed by the levels of related proteins, TrkB and PSD-95, and by the quantification of neurons using Nissl staining. The levels of the two metabolites of the kynurenine (KYN) pathway, 3-hydroxykynurenine (3-HK) and kynurenic acid (KYNA), in the brain were analyzed by LC-MS/MS. Activation of microglia and astrocytes in the brain were also determined by immunohistochemistry and western blotting, respectively. The results showed that, compared with the control group, the mice in the 0.8 mg/kg LPS-treated group exhibited a remarkable increase of immobility time in the tail suspension test. The neuroplasticity of mice in the 0.8 mg/kg LPS-treated group was also significantly reduced. The neurotoxic metabolite, 3-HK, was accumulated significantly in the hippocampus of the 0.8 mg/kg LPS-treated mice. Surprisingly, the 2 mg/kg LPS-treated mice did not exhibit a remarkable change of 3-HK but expressed increased KYNA significantly, which is neuroprotective. Furthermore, the activation of microglia and astrocytes, which were recognized as the primary source of 3-HK and KYNA, respectively, corresponded to the content of these two metabolites of the KYN pathway in each group. Consequently, it was speculated that the homeostasis of different glial cells could lead to a non-linear dose-dependent behavior by regulating the KYN pathway in the LPS-induced depressive-like mice.


Assuntos
Astrócitos/metabolismo , Depressão , Homeostase/efeitos dos fármacos , Cinurenina/metabolismo , Lipopolissacarídeos/toxicidade , Microglia/metabolismo , Animais , Astrócitos/patologia , Comportamento Animal/efeitos dos fármacos , Depressão/induzido quimicamente , Depressão/metabolismo , Depressão/patologia , Masculino , Camundongos , Microglia/patologia
12.
Sci Rep ; 10(1): 3336, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32094406

RESUMO

Depression is still one of challenging, and widely encountered disorders with complex etiology. The role of healthy diet and olive oil in ameliorating depression has been claimed. This study was designed to explore the effects of oleuropein; the main constituent of olive oil; on depression-like behaviors that are induced by repeated administration of corticosterone (40 mg/kg, i.p.), once a day for 21 days, in mice. Oleuropein (8, 16, and 32 mg/kg, i.p.) or fluoxetine (20 mg/kg, positive control, i.p.1) was administered 30 minutes prior to corticosterone injection. Sucrose consumption test, open-field test (OFT), tail suspension test (TST), and forced swimming test (FST) were performed. Reduced Glutathione (GSH), lipid peroxidation, and biogenic amines; serotonin, dopamine, and nor-epinephrine; levels were also analyzed in brain homogenates. Corticosterone treatment induced depression-like behaviors, it increased immobility time in the TST, OFT, and FST, decreased the number of movements in OFT, and decreased sucrose consumption. Corticosterone effect was associated with depletion of reduced glutathione and increase of lipid peroxidation, in addition to modification of biogenic amines; decreased serotonin and dopamine. Oleuropein or fluoxetine administration counteracted corticosterone-induced changes. In conclusion, oleuropein showed a promising antidepressant activity, that is evident by improving corticosterone-induced depression-like behaviors, and normalizing levels of biogenic amines.


Assuntos
Comportamento Animal , Aminas Biogênicas/metabolismo , Depressão/induzido quimicamente , Depressão/metabolismo , Iridoides/farmacologia , Anedonia/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Corticosterona , Depressão/complicações , Modelos Animais de Doenças , Elevação dos Membros Posteriores , Imobilização , Masculino , Camundongos , Movimento , Neurotransmissores/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Sacarose , Natação
13.
J Med Chem ; 63(3): 961-974, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-31944697

RESUMO

Recent studies on sphingolipids suggest that acid sphingomyelinase (ASM), which plays a central role in the pathogenesis of major depression, is emerging to be a novel target for developing antidepressants. Herein we first described the design, synthesis, and biological evaluation of hydroxamic acid-based direct inhibitors of ASM with the effort of validating their antidepressant effects in vivo. As a result, a series of novel ASM inhibitors were developed using a structure-based approach. Our studies demonstrated that the administration of 21b improved depression-like behaviors of rats. Importantly, this positive result was relevant to the inhibition of ASM and the increasing neurogenesis in hippocampus. To the best of our knowledge, this is the first time that direct inhibitors of ASM were developed to support the possibility of ASM as a potential therapeutic target for depression.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Esfingomielina Fosfodiesterase/antagonistas & inibidores , Animais , Antidepressivos/síntese química , Antidepressivos/metabolismo , Linhagem Celular Tumoral , Córtex Cerebral/metabolismo , Depressão/induzido quimicamente , Desenho de Fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/metabolismo , Feminino , Hipocampo/metabolismo , Humanos , Ácidos Hidroxâmicos/síntese química , Ácidos Hidroxâmicos/metabolismo , Simulação de Acoplamento Molecular , Estrutura Molecular , Neurogênese/efeitos dos fármacos , Ligação Proteica , Ratos Sprague-Dawley , Reserpina , Esfingomielina Fosfodiesterase/metabolismo , Relação Estrutura-Atividade
14.
Mol Med Rep ; 21(1): 508-516, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31746394

RESUMO

Depression is often triggered by prolonged exposure to psychosocial stressors and associated with coronary heart disease (CHD). Matrix metalloproteinases (MMPs) are involved in the pathogenesis of various emotional and cardiovascular disorders. The purpose of this study was to investigate whether Kai­Xin­San (KXS), which may terminate the signaling of MMPs, exerts antidepressant­like and cardioprotective effects in a myocardial infarction (MI) plus depression rat model. Rats were randomly assigned to five groups: A normal control (control group), a celisc­injection of isopropyl adrenaline group (ISO group), depression (depression group), an ISO + depression (depression + ISO group), and an ISO + depression group treated with intragastric administration of 1,785 mg/kg KXS (KXS group). Behavioral changes, echocardiography, biochemical index, matrix metalloproteinase (MMP) and apoptosis­related proteins were assessed. Compared with the depression + ISO group, KXS significantly improved stress­induced alterations of behavioral parameters and protected the heart by enlarging the left ventricular (LV) fractional shortening (FS) and LV ejection fraction (EF). Moreover, KXS significantly attenuated ISO + depression­induced MMP­2 and MMP­9 expression at the mRNA and protein level and decreased TIMP in the heart compared to the complex model group. Myocardial apoptosis was significantly attenuated by KXS by regulating the Bcl­2/Bax axis. These results indicated that MI comorbid with depression may damage the MMP balance in the central and peripheral system, and KXS may have a direct anti­depressive and cardio­protective effect by regulating the level of MMPs and associated myocardial apoptosis. It is promising to further explore the clinical potential of KXS for the therapy or prevention of MI plus depression comorbidity disease.


Assuntos
Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Infarto do Miocárdio/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Depressão/induzido quimicamente , Depressão/genética , Depressão/patologia , Modelos Animais de Doenças , Epinefrina/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Humanos , Metaloproteinases da Matriz/genética , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Miocárdio/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos
15.
Food Funct ; 11(1): 378-391, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31820774

RESUMO

The gut microbiota play an important role in many central nervous system diseases through the gut microbiota-brain axis. Recent studies suggest that nicotinamide riboside (NR) has neuroprotective properties. However, it is unknown whether NR can prevent or protect against alcohol-induced depression. Furthermore, it is unclear whether its therapeutic action involves changes in the composition of the gut microbiome. Here, we investigated the effects of NR in the mouse model of alcohol-induced depression. Treatment with NR improved the alcohol-induced depressive behaviour in mice. In addition, NR decreased the number of activated microglia in the hippocampus, and it reduced the levels of pro-inflammatory (IL-1ß, IL-6, and TNF-α) and anti-inflammatory (IL-10 and TGF-ß) cytokines in the brain of mice with alcohol-induced depression. Furthermore, NR significantly upregulated BDNF and diminished the inhibition of the AKT/GSK3ß/ß-catenin signalling pathway in the hippocampus of these mice. 16S rRNA sequencing revealed that, compared with control and NR-treated mice, the gut microbiome richness and composition were significantly altered in the depressed mice. Spearman's correlation analysis showed that differential gut bacterial genera correlated with the levels of inflammation-related cytokines and BDNF in the brain. After faecal microbiota transplantation, cognitive behaviours, microglial activity, levels of cytokines and BDNF, and activation state of the AKT/GSK3ß/ß-catenin signalling pathway (which is downstream of the BDNF receptor, TrkB) in recipient mice were similar to those in donor mice. Collectively, our findings show that NR dietary supplementation protects against alcohol-induced depression-like behaviours, possibly by altering the composition of the gut microbiota.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/terapia , Etanol/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Microglia/efeitos dos fármacos , Niacinamida/análogos & derivados , Animais , Citocinas/metabolismo , Depressão/induzido quimicamente , Modelos Animais de Doenças , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/citologia , Niacinamida/uso terapêutico , RNA Ribossômico 16S
16.
Neurochem Res ; 45(2): 354-370, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31786717

RESUMO

Methylglyoxal (MGO) is a highly reactive dicarbonyl molecule that promotes the formation of advanced glycation end products (AGEs), which are believed to play a key role in a number of pathologies, such as diabetes, Alzheimer's disease, and inflammation. Here, Swiss mice were treated with MGO by intraperitoneal injection to investigate its effects on motor activity, mood, and cognition. Acute MGO treatment heavily decreased locomotor activity in the open field test at higher doses (80-200 mg/kg), an effect not observed at lower doses (10-50 mg/kg). Several alterations were observed 4 h after a single MGO injection (10-50 mg/kg): (a) plasma MGO levels were increased, (b) memory was impaired (object location task), (c) anxiolytic behavior was observed in the open field and marble burying test, and (d) depressive-like behavior was evidenced as evaluated by the tail suspension test. Biochemical alterations in the glutathione and glyoxalase systems were not observed 4 h after MGO treatment. Mice were also treated daily with MGO at 0, 10, 25 and 50 mg/kg for 11 days. From the 5th to the 11th day, several behavioral end points were evaluated, resulting in: (a) absence of motor impairment as evaluated in the open field, horizontal bars and pole test, (b) depressive-like behavior observed in the tail suspension test, and (c) cognitive impairments detected on working, short- and long-term memory when mice were tested in the Y-maze spontaneous alternation, object location and recognition tests, and step-down inhibitory avoidance task. An interesting finding was a marked decrease in dopamine levels in the prefrontal cortex of mice treated with 50 mg/kg MGO for 11 days, along with a ~ 25% decrease in the Glo1 content. The MGO-induced dopamine depletion in the prefrontal cortex may be related to the observed memory deficits and depressive-like behavior, an interesting topic to be further studied as a potentially novel route for MGO toxicity.


Assuntos
Ansiolíticos/toxicidade , Depressão/induzido quimicamente , Dopamina/metabolismo , Transtornos da Memória/induzido quimicamente , Córtex Pré-Frontal/efeitos dos fármacos , Aldeído Pirúvico/toxicidade , Animais , Depressão/metabolismo , Feminino , Lactoilglutationa Liase/metabolismo , Locomoção/efeitos dos fármacos , Memória/efeitos dos fármacos , Transtornos da Memória/metabolismo , Camundongos , Córtex Pré-Frontal/metabolismo
17.
J Affect Disord ; 260: 302-313, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521867

RESUMO

BACKGROUND: Metformin, a first-line antiglycemic drug, has been reported to have anti-depressant effects in patients with type 2 diabetes; however, its exact role and underlying mechanism still need to be investigated. METHOD: C57BL/6J mice were subjected to the Chronic social defeat stress (SDS) and drug administration (Control + Vehicle, SDS + Vehicle, SDS + MET (200 mg kg-1), SDS + FLUOX (3 mg kg-1), SDS + MET + FLUOX). And the depression phenotypes were evaluated by the sucrose preference test, social interaction, tail suspension test and forced swimming test. The potential mechanisms underlying the effects of metformin on depression was discussed by using Chromatin immunoprecipitation, Quantitative real-time PCR mRNA expression analysis and Western blot in vivo and in primary cultured hippocampal neurons. RESULT: The metformin treatment counteracted the development of depression-like behaviors in mice suffering SDS when administered alone and enhanced the anti-depressant effect of fluoxetine when combined with fluoxetine. Further RNA sequencing analysis revealed that metformin treatment prevented the transcriptional changes in the medial prefrontal cortex (mPFC) of the animals and Golgi staining indicated favorable morphological changes in the neurite plasticity of CA1 pyramidal neurons, which approximated to those found in unstressed mice. At a molecular level, metformin significantly upregulated the expression of the brain-derived neurotrophic factor (BDNF) by increasing the histone acetylation along with the BDNF promoter, which was attributed to the activation of AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB). CONCLUSION: Our findings suggest that metformin can produce antidepressant effects, which provides empirical insights into the clinical value of metformin in the prevention and therapy of depression.


Assuntos
Acetilação/efeitos dos fármacos , Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Depressão/tratamento farmacológico , Metformina/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Depressão/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/psicologia , Modelos Animais de Doenças , Fluoxetina/farmacologia , Hipocampo/metabolismo , Histonas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Psicológico/induzido quimicamente , Estresse Psicológico/tratamento farmacológico , Natação
18.
J Dermatolog Treat ; 31(7): 734-738, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30985218

RESUMO

Background: The vulnerable brain regions to isotretinoin are represented as hippocampus and prefrontal cortex, involved in mood regulation as well as coordination of cognitive functions. Adolescence is a critical period with dynamic alterations in neurocognition. Isotretinoin brought concerns about its possible effects on executive functions, attention and memory.Objective: Evaluate the impacts of isotretinoin on neurocognitive functions in adolescents with acne vulgaris and determine the emergence of psychiatric side effects.Materials and methods: Fifty-five adolescent acne vulgaris patients were assigned to either isotretinoin (n = 38) or systemic antibiotic (n = 17) groups. The neuropsychological test battery and psychometric tests were performed before treatment and during treatment with 3-months intervals.Results: Stroop-TBAG form, verbal-auditory digit span, controlled oral word association test and trail making test results improved in the isotretinoin treatment group along with stable scores in the antibiotic group. Children Depression Scale scores of the isotretinoin group showed an increase at 6th month compared to baseline. None of the patients was evaluated as depressive by the psychiatric examination.Conclusions: In a vulnerable age group, our results demonstrate an improvement for neurocognitive functions in isotretinoin patients. The conflicting results suggest distinct mechanisms to be responsible for the effects on affective and cognitive functions.


Assuntos
Acne Vulgar/tratamento farmacológico , Ansiedade , Cognição/efeitos dos fármacos , Depressão , Fármacos Dermatológicos/farmacologia , Isotretinoína/farmacologia , Acne Vulgar/psicologia , Adolescente , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ansiedade/induzido quimicamente , Criança , Depressão/induzido quimicamente , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Feminino , Humanos , Isotretinoína/efeitos adversos , Isotretinoína/uso terapêutico , Masculino , Testes Neuropsicológicos , Estudos Prospectivos , Psicometria
19.
Psychiatry Res ; 284: 112691, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791704

RESUMO

Emerging evidence indicates that disruption of the intestinal flora play an important role in the pathogenesis of depression. As one of the causes of such disturbances, the role of antibiotics in depression risk is gradually being revealed. Herein, we review recent findings showing that the use of both single and multiple antibiotic regimens may be related to depression by changing the gut microbiota and the brain-gut axis. Based on recent discoveries, we also suggest that several brain-gut interactive mechanisms (particularly those involving nerve and glial cells, neurotransmitters, brain neurotrophic factors, inflammatory factors, short-chain fatty acids, circulating metabolites, blood-brain barrier, and oxidative stress) may help understand the effects of antibiotics on intestinal flora and its relationship with depression.


Assuntos
Antibacterianos/efeitos adversos , Encéfalo/efeitos dos fármacos , Depressão/induzido quimicamente , Depressão/psicologia , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Depressão/metabolismo , Microbioma Gastrointestinal/fisiologia , Humanos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia
20.
J Dermatolog Treat ; 31(4): 415-421, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30897009

RESUMO

Androgenic alopecia (AGA) is an esthetic condition with varying psycho-social implications, easily accepted by some patients and tolerated only with difficulty by others. Modern therapeutic options such as 5α-reductase inhibitors have significant outcomes, but also exert significant side effects in a subset of patients. The literature describes three distinct situations regarding finasteride administration, a compound largely used for AGA. Some studies show finasteride to be very safe with minimal or no side effects. Other studies take a more cautious approach, recognizing such side effects but, at the same time, considering the putative relationship between finasteride and adverse effects to be disputable, given that placebo administration in AGA is associated with relatively similar or even more severe side effects. Finally, some authors/studies are concerned that, when compared to placebo, finasteride administration may result in side effects with greater frequency and severity, and sometimes that persist even after treatment cessation in the form of post-finasteride syndrome. Several factors presented in this paper appear to explain finasteride inconsistency regarding its therapeutic and side effects. Such factors should be further investigated and used to categorize subjects into distinct subgroups, either predisposed to adverse reactions or more tolerant of the finasteride administration.


Assuntos
Inibidores de 5-alfa Redutase/efeitos adversos , Alopecia/tratamento farmacológico , Finasterida/efeitos adversos , Inibidores de 5-alfa Redutase/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Depressão/induzido quimicamente , Feminino , Finasterida/uso terapêutico , Humanos , Masculino
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