Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.168
Filtrar
1.
Mol Cell Biochem ; 465(1-2): 65-73, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894530

RESUMO

Curcumin (Cur) is widely used as an anti-inflammation agent and has anti-depression potential. Neuroinflammation mediated by Ca2+ channel activation is closely associated with the progression of post-stroke depression (PSD). In the current study, the role of P2X7 receptor (P2X7R) in the anti-PSD function of Cur was explored. Rats were subjected to middle cerebral artery occlusion (MCAO) surgery and chronic mild stress administration to induce PSD symptoms and then treated with Cur. The behaviors of rats were assessed with sucrose preference and forced swim tests. The accumulation of Ca2+ and the systemic inflammatory response in rats were detected. To determine the role of P2X7R in the anti-PSD function of curcumin, the PSD mice were further administrated with P2X7R agonist and antagonist. The administration of Cur attenuated behavior disorders associated with PSD. Moreover, the Ca2+ accumulation and the inflammatory response associated with PSD were also blocked by Cur. Cur also inhibited the activation of Ca2+ channel. The induced activity of P2X7R blocked the function of Cur by maintaining the symptoms of PSD in Cur-treated rats. Collectively, the anti-PSD function of Cur was dependent on the inhibition of P2X7R, which then deactivated Ca2+ channel-mediated inflammatory response associated with PSD progression.


Assuntos
Sinalização do Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Curcumina/farmacologia , Microglia/metabolismo , Agonistas do Receptor Purinérgico P2X/farmacologia , Receptores Purinérgicos P2X7/metabolismo , Animais , Depressão/metabolismo , Depressão/patologia , Masculino , Microglia/patologia , Antagonistas do Receptor Purinérgico P2X/farmacologia , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia
2.
Ann Hematol ; 98(12): 2683-2691, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31745600

RESUMO

In Germany, analyses of clinical and laboratory features of patients with acute porphyrias are only available for hereditary coproporphyria (HCP) but not with other acute porphyrias, acute intermittent porphyria (AIP) and variegate porphyria (VP). The aim of the study was to analyze a large cohort of patients with particular focus upon quality of life aspects. Sixty-two individuals from separate families with acute porphyrias (57 AIP, 5 VP) were included into an observational study collecting biochemical, genetic, and clinical data. A questionnaire was designed to complete anamnestic information and to assess the influence on quality of life. Most frequent signs and symptoms or laboratory abnormalities were abdominal colicky pain, red coloration of urine, and hyponatremia. Depression or anxiety was reported by 61% or 52% individuals, respectively. Fatigue was mentioned as the most quality of life-limiting symptom. In 59/61 patients, mutations could be identified. 44% (20/45) had to be admitted to an intensive care unit. Heme arginate was used in 64% (29/45) of patients for treatment of acute attacks at least once and in 33% for long-term treatment with high frequency of administration. Serum creatinine values increased in 47% (7/17) of the patients with recurrent attacks. Our analysis confirms a substantial influence of the diseases on the quality of life on patients. Percentages of urine discoloration and intensive care unit admissions were much higher than in other reports. Long-term treatment with heme arginate requires careful monitoring of iron status and renal values.


Assuntos
Arginina/administração & dosagem , Família , Heme/administração & dosagem , Hospitalização , Porfiria Aguda Intermitente , Qualidade de Vida , Inquéritos e Questionários , Adulto , Ansiedade/tratamento farmacológico , Ansiedade/genética , Ansiedade/metabolismo , Ansiedade/psicologia , Depressão/tratamento farmacológico , Depressão/genética , Depressão/metabolismo , Depressão/psicologia , Feminino , Alemanha , Humanos , Masculino , Porfiria Aguda Intermitente/tratamento farmacológico , Porfiria Aguda Intermitente/genética , Porfiria Aguda Intermitente/metabolismo , Porfiria Aguda Intermitente/psicologia , Estudos Prospectivos
3.
Acta Neurobiol Exp (Wars) ; 79(3): 232-237, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587015

RESUMO

Emotional stress is considered a serious pathogenetic factor of depression. In this study an ultrasound model of emotional stress developed in our laboratory was applied. It is characterized by the use of ultrasound as the stressor agent. Animals are triggered not by any organic or physical disturbances but by the perception of adverse information. This type of stress can induce depressive-like behavioral changes in rodents, manifested by decreased sucrose preference and increased time of immobility in a forced swim test. Ultrasound stress also increased the levels of oxidative stress markers. This is important, as stress has an established association with increased oxidative processes in the central nervous system. Total glutathione and carbonyl protein content were selected as relevant brain markers, as glutathione plays a critical role in cellular defensive mechanisms during oxidative stress and the level of protein carbonyls can be a measure of global protein oxidation. We demonstrated that two weeks of chronic exposure to ultrasound was enough to cause depressive-like behavioral changes in rats. Increased levels of oxidative stress markers in the hippocampus and prefrontal cortex were also observed after two weeks of such stress. The current study has two goals: the first is to study the relationship of depression and oxidative stress; the second is an additional validation of our approach to modeling stress­induced depressive-like states in rats. The present data further support the validity of the ultrasound model by expanding information related to the influence of ultrasound stress on behavioral and physiological parameters, which are of great importance in the development of stress-induced depression. A time correlation between the onset of symptoms and a change in the level of oxidative stress markers in the brain is also demonstrated.


Assuntos
Comportamento Animal/fisiologia , Depressão/fisiopatologia , Estresse Oxidativo/fisiologia , Estresse Psicológico/fisiopatologia , Animais , Depressão/metabolismo , Transtorno Depressivo/fisiopatologia , Modelos Animais de Doenças , Glutationa/metabolismo , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Córtex Pré-Frontal/fisiopatologia , Ratos
4.
Molecules ; 24(20)2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31618892

RESUMO

Icariin is a prenylated flavonol glycoside isolated from Epimedium herb, and has been shown to be its main bioactive component. Recently, the antidepressant-like mechanism of icariin has been increasingly evaluated and demonstrated. However, there are few studies that have focused on the involvement of the phosphatidylinositol 3-kinase (PI3K)/serine-threonine protein kinase (AKT) signaling in mediating the perimenopausal depression effects of icariin. Perimenopausal depression is a chronic recurrent disease that leads to an increased risk of suicide, and poses a significant risk to public health. The aim of the present study was to explore the effect of icariin on the expression of the PI3K-AKT pathway related to proteins in a rat model of perimenopausal depression. Eighty percent of the left ovary and the entire right ovary were removed from the model rats. A perimenopausal depression model was created through 18 days of chronic unpredictable stimulation, followed by the gavage administration of target drugs for 30 consecutive days. We found that icariin administered at various doses significantly improved the apparent symptoms in the model rats, increased the organ indices of the uterus, spleen, and thymus, and improved the pathological changes in the ovaries. Moreover, icariin administration elevated the serum levels of female hormone estradiol (E2), testosterone (T), and interleukin (IL)-2, decreased those of follicle stimulating hormone (FSH) and luteotropic hormone (LH), promoted the expression levels of estrogen receptor (ER) and ERα in the hypothalamus, and increased those of serotonin (5-HT), dopamine (DA), and noradrenaline (NA) in the brain homogenate. Furthermore, icariin elevated the expression levels of AKT, phosphorylation-akt (p-AKT), PI3K (110 kDa), PI3K (85 kDa), and B-cell lymphoma 2 (Bcl-2) in the ovaries, and inhibited those of Bax. These results show that icariin administration rebalanced the disordered sex hormones in perimenopausal depression rats, regulated the secretion of neurotransmitters in the brain, boosted immune function, and improved the perimenopausal syndrome. The mechanism of action may be related to the regulation of the expression of PI3K-AKT pathway-related proteins.


Assuntos
Flavonoides/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Comportamento Animal , Biomarcadores , Depressão/etiologia , Depressão/metabolismo , Depressão/psicologia , Modelos Animais de Doenças , Feminino , Ovário/metabolismo , Perimenopausa/psicologia , Ratos , Receptores Estrogênicos/metabolismo
5.
J Physiol Pharmacol ; 70(3)2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31539886

RESUMO

A balanced maternal diet is necessary for the proper health and development of offspring. Recent clinical and preclinical studies have strongly indicated that maternal exposure to a high-fat diet (HFD) can have an irreversible impact on the structure and function of the offspring's brain and affect the immune system, which may predispose the offspring to brain disorders, including depression. The irisin/brain-derived neurotrophic factor (BDNF) axis is a pathway that influences several neurobehavioral mechanisms involved in the pathogenesis of mental disorders. The aim of the present study was to evaluate the influence of a maternal HFD during pregnancy and lactation on depressive-like behavior, serum irisin concentration and hippocampal levels of irisin, BDNF and inflammatory factors (interleukin-1α, interleukin-6 and tumor necrosis factor-α) in adolescent and adult male and female offspring. The main findings indicate that offspring exposed to a maternal HFD are characterized by an increased immobility time in the forced swimming test at both stages of life. Our results showed that a maternal HFD decreased serum and hippocampal irisin levels in females on postnatal day (PND) 28 and decreased the level of interleukin-1α at postnatal days 28 and 63 in the hippocampus. Interestingly, significant age-dependent changes were observed in irisin, BDNF and interleukin levels. To summarize, our study indicates that a maternal HFD during pregnancy and lactation provokes depressive-like behaviour in the offspring. However, despite the observed changes in the levels of irisin and IL-1α in females, further investigations are required to identify the underlying molecular mechanism associated with depressive-like behavior in the offspring of HFD-fed dams.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/metabolismo , Dieta Hiperlipídica/efeitos adversos , Lactação/metabolismo , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Animais , Comportamento Animal , Feminino , Hipocampo/metabolismo , Masculino , Gravidez , Ratos
6.
Molecules ; 24(18)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31540539

RESUMO

Treatment of the unpredictable chronic mild stress (UCMS) mice with the ethanol extract of Dipterocarpus alatus leaf attenuated anhedonia (increased sucrose preference) and behavioral despair (decreased immobility time in tail suspension test (TST) and forced swimming test (FST)). The extract not only decreased the elevation of serum corticosterone level and the index of over-activation of the hypothalamic-pituitary-adrenal (HPA) axis, caused by UCMS, but also ameliorated UCMS-induced up-regulation of serum- and glucocorticoid-inducible kinase 1 (SGK1) mRNA expression and down-regulation of cyclic AMP-responsive element binding (CREB) and brain-derived neurotrophic factor (BDNF) mRNAs in frontal cortex and hippocampus. In vitro monoamine oxidase (MAO) inhibition assays showed that the extract exhibited the partial selective inhibition on MAO-A. HPLC analysis of the extract showed the presence of flavonoids (luteolin-7-O-glucoside, kaempferol-3-glucoside, rutin) and phenolic acids (gallic acid, ferulic acid, and caffeic acid) as major constituents.


Assuntos
Depressão , Dipterocarpaceae/química , Etanol/química , Extratos Vegetais , Folhas de Planta/química , Estresse Psicológico , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Depressão/patologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/patologia , Proteínas Imediatamente Precoces/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos ICR , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/patologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteínas Serina-Treonina Quinases/biossíntese , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Estresse Psicológico/patologia
7.
Nat Commun ; 10(1): 3924, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477731

RESUMO

The serotonergic system and in particular serotonin 1A receptor (5-HT1AR) are implicated in major depressive disorder (MDD). Here we demonstrated that 5-HT1AR is palmitoylated in human and rodent brains, and identified ZDHHC21 as a major palmitoyl acyltransferase, whose depletion reduced palmitoylation and consequently signaling functions of 5-HT1AR. Two rodent models for depression-like behavior show reduced brain ZDHHC21 expression and attenuated 5-HT1AR palmitoylation. Moreover, selective knock-down of ZDHHC21 in the murine forebrain induced depression-like behavior. We also identified the microRNA miR-30e as a negative regulator of Zdhhc21 expression. Through analysis of the post-mortem brain samples in individuals with MDD that died by suicide we find that miR-30e expression is increased, while ZDHHC21 expression, as well as palmitoylation of 5-HT1AR, are reduced within the prefrontal cortex. Our study suggests that downregulation of 5-HT1AR palmitoylation is a mechanism involved in depression, making the restoration of 5-HT1AR palmitoylation a promising clinical strategy for the treatment of MDD.


Assuntos
Encéfalo/fisiopatologia , Depressão/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Receptor 5-HT1A de Serotonina/metabolismo , Aciltransferases/genética , Aciltransferases/metabolismo , Animais , Encéfalo/metabolismo , Linhagem Celular Tumoral , Depressão/genética , Depressão/metabolismo , Transtorno Depressivo Maior/genética , Regulação da Expressão Gênica , Humanos , Lipoilação , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Ratos Wistar , Receptor 5-HT1A de Serotonina/genética
8.
Exp Neurol ; 322: 113058, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31499061

RESUMO

Evidence indicates that depression is closely related to hyperactivity of the lateral habenula (LHb). However, it is not clear how activation and blockade of AMPA receptors (AMPARs) in the LHb affect depressive-like behaviors, particularly in Parkinson's disease-related depression. In this study, unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc) in rats induced depressive-like behaviors and led to hyperactivity of LHb neurons compared to SNc sham-lesioned rats. Interestingly, intra-LHb injection of AMPAR agonist (S)-AMPA produced antidepressant-like effects in the two groups of rats and antagonist NBQX induced depressive-like behaviors, although (S)-AMPA excited LHb neurons and NBQX inhibited these neurons. We further found that intra-LHb injection of (S)-AMPA excited dopaminergic neurons in the anterior ventral tegmental area (aVTA) and serotonergic neurons in the dorsal raphe nucleus (DRN), which increased release of DA and 5-HT in the medial prefrontal cortex (mPFC), while NBQX induced the opposite effects. Further, lesioning the GABAergic rostromedial tegmental nucleus did not alter the proportions of the responses of these neurons to AMPAR stimulation. Additionally, lesions of the SNc reduced the level of p-GluR2-S880 in the LHb, which can increase the surface expression of calcium-impermeable GluR2-containing AMPARs (CI-AMPARs). This change in SNc-lesioned rats enhanced effects of (S)-AMPA and NBQX on the behaviors, LHb neuronal firing and release of DA and 5-HT. Collectively, antidepressant-like effects produced by (S)-AMPA attribute to activation of LHb neurons expressing CI-AMPAR, which excites aVTA dopaminergic neurons and DRN serotonergic neurons via the direct projection, thereby increasing release of mPFC DA and 5-HT.


Assuntos
Depressão/metabolismo , Habenula/metabolismo , Transtornos Parkinsonianos/metabolismo , Receptores de AMPA/metabolismo , Animais , Depressão/etiologia , Masculino , Transtornos Parkinsonianos/complicações , Ratos , Ratos Sprague-Dawley
9.
Int J Mol Sci ; 20(17)2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31480539

RESUMO

An olfactory bulbectomy (OBX) rodent is a widely-used model for depression (especially for agitated depression). The present study aims to investigate the hippocampus metabolic profile and autophagy-related pathways in OBX rats and to explore the modulatory roles of fluoxetine. OBX rats were given a 30-day fluoxetine treatment after post-surgery rehabilitation, and then behavioral changes were evaluated. Subsequently, the hippocampus was harvested for metabonomics analysis and Western blot detection. As a result, OBX rats exhibited a significantly increased hyperemotionality score and declined spatial memory ability. Fluoxetine reduced the hyperemotional response, but failed to restore the memory deficit in OBX rats. Sixteen metabolites were identified as potential biomarkers for the OBX model including six that were rectified by fluoxetine. Disturbed pathways were involved in amino acid metabolism, fatty acid metabolism, purine metabolism, and energy metabolism. In addition, autophagy was markedly inhibited in the hippocampus of OBX rats. Fluoxetine could promote autophagy by up-regulating the expression of LC3 II, beclin1, and p-AMPK/AMPK, and down-regulating the levels of p62, p-Akt/Akt, p-mTOR/mTOR, and p-ULK1/ULK1. Our findings indicated that OBX caused marked abnormalities in hippocampus metabolites and autophagy, and fluoxetine could partly redress the metabolic disturbance and enhance autophagy to reverse the depressive-like behavior, but not the memory deficits in OBX rats.


Assuntos
Autofagia , Depressão/metabolismo , Modelos Animais de Doenças , Fluoxetina/farmacologia , Hipocampo/metabolismo , Transtornos da Memória , Animais , Antidepressivos de Segunda Geração/farmacologia , Depressão/tratamento farmacológico , Depressão/fisiopatologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Masculino , Redes e Vias Metabólicas , Bulbo Olfatório/cirurgia , Ratos , Ratos Sprague-Dawley
10.
BMC Complement Altern Med ; 19(1): 240, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484532

RESUMO

BACKGROUND: Major depression is an important complication in patients with breast cancer, but is an underrecognized and undertreated condition in this population. The Baihe Zhimu Tang (BZ formula) is a traditional Chinese formula consisting of Lilium brownii var. viridulum Baker (L. brownii) and Anemarrhena asphodeloides (A. asphodeloides) Bunge that is used for the treatment of depression. However, the interaction between tamoxifen and BZ formula is frequently overlooked by traditional and alternative medical doctors. In the present study, the influence of BZ formula on the effectiveness of tamoxifen in breast cancer in mice and the effects of tamoxifen on the antidepressant effect of BZ formula and its major components mangiferin and timosaponin BII in mice were investigated. METHODS: Identification of the major components of BZ formula was performed using fast HPLC-tandem mass spectrometry (HPLC-MS/MS). The main flavonoids and saponins in A. asphodeloides were determined by HPLC-UV and HPLC-ELSD, separately. The antidepressant efficacy of BZ formula was evaluated using a mouse tail-suspension test. The effects of BZ formula on the antineoplastic activity of tamoxifen were performed in a mouse xenograft model of human breast cancer MCF-7 cells. P450 activity was determined using microsomal incubations by HPLC-MS/MS. Measurement of serum concentrations of tamoxifen and its metabolites was used by HPLC-MS/MS. RESULTS: BZ formula attenuated the effectiveness of tamoxifen treatment of breast cancer and reduced the concentrations of endoxifen and 4-OH-tamoxifen in tumor-bearing mice. Of two of the major components of BZ formula, the antidepressant effect of mangiferin, but not timosaponin BII, was significantly inhibited by tamoxifen in mice. BZ formula and its component mangiferin also significantly inhibited CYP450 enzyme activity in rat liver microsomes. CONCLUSION: BZ formula attenuated the effectiveness of tamoxifen in treatment of breast cancer in mice by influencing CYP450 enzymes. The present study laid a foundation for the treatment of patients with breast cancer and depression by BZ formula or other Chinese herbal formulas containing A. asphodeloides.


Assuntos
Antineoplásicos Hormonais/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Mamárias Experimentais/metabolismo , Tamoxifeno/farmacologia , Animais , Antineoplásicos Hormonais/farmacocinética , Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Depressão/metabolismo , Interações de Medicamentos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Feminino , Humanos , Células MCF-7 , Masculino , Camundongos , Camundongos Endogâmicos ICR , Camundongos Nus , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Ratos , Tamoxifeno/farmacocinética
11.
Food Funct ; 10(9): 6062-6073, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31486445

RESUMO

Depression is a mental disorder that brings severe burdens to patients and their families. Neuroinflammation and neurotrophins are involved in depression. Lotus plumule is a nutritional food with medicinal values. In the present study, we tried to clarify the anti-depressive effect and molecular mechanism of lotus plumule. Network pharmacological analysis, behavior tests, qRT-PCR and western blotting were used. We found 7 potential active components and 91 targets from the TCMSP database. KEGG analysis suggested that lotus plumule significantly affected nitrogen metabolism, calcium signaling, and inflammatory mediator regulation signaling pathways. Consistent with those effects, total alkaloids of lotus plumule (TLA) and active alkaloids differently suppressed the nitric oxide (NO) production and pro-inflammatory mediators. TLA and higenamine significantly ameliorated LPS-induced depression-like behavior, increased BDNF levels, suppressed microglia activation, and inhibited the expression of ER stress-related proteins. Meanwhile, TLA and higenamine activated microglia autophagy by increasing the beclin-1 and LC3B-II expression. Additionally, in the presence of autophagy inhibitor 3-MA, TLA and higenamine did not reduce the LPS-induced NO production or pro-inflammatory mediators. Collectively, TLA and higenamine attenuated LPS-induced depression-like behavior by regulating BDNF-mediated ER stress and autophagy. Therefore, drinking tea of lotus plumule may provide a potential strategy for preventing depression.


Assuntos
Alcaloides/administração & dosagem , Depressão/tratamento farmacológico , Lotus/química , Extratos Vegetais/administração & dosagem , Animais , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/induzido quimicamente , Depressão/metabolismo , Depressão/psicologia , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Lipopolissacarídeos/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Sementes/química
12.
Oxid Med Cell Longev ; 2019: 5813985, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396300

RESUMO

Background: The mechanisms of crosstalk between depression and gastric cancer (GC) remain ill defined. Given that reactive oxygen species (ROS) is involved in the pathophysiology of both GC and depression, we try to explore the activities of ROS in the development of GC and GC-related depression. Methods: 110 patients with newly diagnosed GC were recruited in our study. The clinical characteristics of these patients were recorded. Inflammation and oxidative stress markers were detected by ELISA. The depression status of patients with GC was assessed during follow-up. The association between ROS, ABL1, and inflammation factors was evaluated in H2O2-treated GC cell lines and The Cancer Genome Atlas (TCGA) database. The effect of ABL1 on inflammation was detected with Imatinib/Nilotinib-treated GC cell lines. A chronic mild stress- (CMS-) induced patient-derived xenograft (PDX) mice model was established to assess the crosstalk between depression and GC. Results: Depression was correlated with poor prognosis of patients with GC. GC patients with depression were under a high level of oxidative status as well as dysregulated inflammation. In the CMS-induced GC PDX mice model, CMS could facilitate the development of GC. Additionally, tumor bearing could induce depressive-like behaviors of mice. With the treatment of ROS, the activities of ABL1 and inflammatory signaling were enhanced both in vitro and in vivo, and blocking the activities of ABL1 inhibited inflammatory signaling. Conclusions: ROS-activated ABL1 mediates inflammation through regulating NF-κB1 and STAT3, which subsequently leads to the development of GC and GC-related depression.


Assuntos
Depressão/etiologia , Proteínas Proto-Oncogênicas c-abl/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Neoplasias Gástricas/diagnóstico , /sangue , Animais , Antineoplásicos/farmacologia , Comportamento Animal/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Depressão/metabolismo , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Mesilato de Imatinib/farmacologia , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Nus , Prognóstico , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/complicações
13.
Psychopharmacology (Berl) ; 236(8): 2389-2403, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31375849

RESUMO

RATIONALE: According to psychological theories, cognitive distortions play a pivotal role in the aetiology and recurrence of mood disorders. Although clinical evidence for the coexistence of depression and altered sensitivity to performance feedback is relatively coherent, we still do not know whether increased or decreased sensitivity to positive or negative feedback is associated with 'pro-depressive' profile in healthy subjects. OBJECTIVE: Our research has been designed to answer this question, and here, we present the first steps in that direction. METHODS: Using a rat version of the probabilistic reversal-learning (PRL) paradigm, we evaluated how sensitivity to negative and positive feedback influences other cognitive processes associated with mood disorders, such as motivation in the progressive ratio schedule of reinforcement (PRSR) paradigm, hedonic status in the sucrose preference (SP) test, locomotor and exploratory activity in the open field (OF) test, and anxiety in the light/dark box (LDB) test. RESULTS: The results of our study demonstrated for the first time that in rodents, sensitivity to negative and positive feedback could be considered a stable and enduring behavioural trait. Importantly, we also showed that these traits are independent of each other and that trait sensitivity to positive feedback is associated with cognitive flexibility in the PRL test. The computational modelling results also revealed that in animals classified as sensitive to positive feedback, the α learning rates for both positive and negative reward prediction errors were higher than those in animals classified as insensitive. We observed no statistically significant interactions between sensitivity to negative or positive feedback and the parameters measured in the PRSR, SP, OF or LDB tests. CONCLUSIONS: Further studies using animal models of depression based on chronic stress should reveal whether sensitivity to feedback is a latent trait that when interacts with stressful life events, could produce correlates of depressive symptoms in rats.


Assuntos
Retroalimentação Fisiológica/fisiologia , Locomoção/fisiologia , Motivação/fisiologia , Esquema de Reforço , Reversão de Aprendizagem/fisiologia , Recompensa , Animais , Ansiedade/metabolismo , Ansiedade/psicologia , Simulação por Computador , Depressão/metabolismo , Depressão/psicologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
14.
Life Sci ; 234: 116751, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31415771

RESUMO

AIMS: The present study aims to investigate the impacts of olfactory bulbectomy (OBX) on urinary metabolic profile and tryptophan metabolites in prefrontal cortex (PFC) of rats, and to explore the regulation effects of fluoxetine. MAIN METHODS: OBX model was developed by aspiration of olfactory bulbs. After fluoxetine treatment (10 mg/kg) for 14 days, urine samples were collected and behavior tests were applied. Tryptophan (TRP) metabolites and neurotransmitters in PFC were determined by prominence ultrafast liquid chromatography-QTRAP-mass spectrometry, and tryptophan hydroxylase 2 (TPH2) and indoleamine-2,3-dioxygenase 1 (IDO1) were evaluated by western blot. Urinary metabolites were analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry-based metabonomics strategy. KEY FINDING: OBX rats showed hyperlocomotion in open field, hyperactivity in open arm and despair status, and fluoxetine reserved these behavioral abnormalities. The levels of TRP, 5-HIAA, 5-HIAA/5-HT ratio and DA increased, while kynurenine and 5-HT decreased in PFC of OBX rats. The activities of TPH2 and IDO1were inhibited after OBX. Twenty-six altered metabolites were identified as potential biomarkers in OBX rats involved in tryptophan metabolism, gut microbiota metabolism, energy metabolism, purine metabolism, ascorbate and aldarate metabolism, and tyrosine metabolism. Among them, 15 abnormal metabolites were corrected by fluoxetine to some extent. SIGNIFICANCE: Our results revealed that urinary metabolic profile changed greatly in OBX rats, and identified biomarkers might be helpful for the diagnosis of agitated depression. The regulation effects of fluoxetine on urinary metabolic profile and tryptophan metabolites in PFC might contribute to its antidepressant action in OBX rats.


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Depressão/tratamento farmacológico , Depressão/metabolismo , Fluoxetina/uso terapêutico , Metaboloma/efeitos dos fármacos , Animais , Antidepressivos de Segunda Geração/farmacologia , Depressão/urina , Modelos Animais de Doenças , Fluoxetina/farmacologia , Masculino , Bulbo Olfatório/cirurgia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Ratos Sprague-Dawley , Triptofano/metabolismo
15.
BMC Complement Altern Med ; 19(1): 215, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412844

RESUMO

BACKGROUND: Mounting evidence indicates that the cerebral cortex is an important physiological system of emotional activity, and its dysfunction may be the main cause of stress. Glutamate is the primary excitatory neurotransmitter in the central nervous system (CNS), which initiates rapid signal transmission in the synapse before its reuptake into the surrounding glia, specifically astrocytes (ASTs). The astrocytic excitatory amino acid transporters 1 (EAAT1) and 2 (EAAT2) are the major transporters that take up synaptic glutamate to maintain optimal extracellular glutamic levels, thus preventing accumulation in the synaptic cleft and ensuing excitotoxicity. Growing evidence has shown that excitotoxicity is associated with depression. Therefore, we hypothesized that the underlying antidepressant-like mechanism of Xiaoyaosan (XYS), a Chinese herbal formula, may be related to the regulation of astrocytic EAATs. Therefore, we studied the antidepressant mechanism of XYS on the basis of EAAT dysfunction in ASTs. METHODS: Eighty adult C57BL/6 J mice were randomly divided into 4 groups: a control group, a chronic unpredictable mild stress (CUMS) group, a Xiaoyaosan (XYS) treatment group and a fluoxetine hydrochloride (Flu) treatment group. Except for the control group, mice in the other groups all received chronic unpredictable mild stress for 21 days. Mice in the control and CUMS groups received gavage administration with 0.5 mL of normal saline (NS) for 21 days, and mice in the XYS and Flu treatment groups were administered dosages of 0.25 g/kg/d and 2.6 mg/kg/d by gavage. The effects of XYS on the depressive-like behavioral tests, including the open field test (OFT), forced swimming test (FST) and sucrose preference test (SPT), were examined. The glutamate (Glu) concentrations of the prefrontal cortex (PFC) were detected with colorimetry. The morphology of neurons in the PFC was observed by Nissl staining. The expression of glial fibrillary acidic protein (GFAP), NeuN, EAAT1 and EAAT2 proteins in the PFC of mice was detected by using Western blotting and immunohistochemistry. Quantitative real-time PCR (qPCR) was used to detect the expression of the GFAP, NeuN, EAAT1 and EAAT2 genes in the PFC of mice. RESULTS: The results of behavioral tests showed that CUMS-induced mice exhibited depressive-like behavior, which could be improved in some tests with XYS and Flu treatment. Immunohistochemistry and Western blot analysis showed that the protein levels of GFAP, NeuN, EAAT1 and EAAT2 in the PFC of CUMS mice were significantly lower than those in the control group, and these changes could be reversed by XYS and Flu. The results of qPCR analysis showed that the expression of GFAP, NeuN, EAAT1 and EAAT2 mRNAs in the PFC of CUMS mice was not significantly changed, with the exception of EAAT2, compared with that of the control group, while the expression of the above mRNAs was significantly higher in the XYS and Flu groups than that in the CUMS group. CONCLUSION: XYS may exert antidepressant-like effects by improving the functions of AST and EAATs and attenuating glutamate-induced neuronal damage in the frontal cortex.


Assuntos
Antidepressivos/administração & dosagem , Astrócitos/efeitos dos fármacos , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Transportador 1 de Aminoácido Excitatório/metabolismo , Transportador 2 de Aminoácido Excitatório/metabolismo , Córtex Pré-Frontal/citologia , Animais , Comportamento Animal , Depressão/genética , Depressão/metabolismo , Modelos Animais de Doenças , Transportador 1 de Aminoácido Excitatório/genética , Transportador 2 de Aminoácido Excitatório/genética , Proteína Glial Fibrilar Ácida/metabolismo , Ácido Glutâmico/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/efeitos dos fármacos
16.
Neuropeptides ; 77: 101959, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31445676

RESUMO

Several experimental studies have proved that activation of neuroinflammation pathways may contribute to the development of depression, a neuropsychiatric disorder disease. Our previous studies have shown the antidepressant properties of apelin, but the mechanism was unkown. This study was performed to verify whether the antidepressant effect of apelin was related to its anti-inflammation effect in the central nervous system. To achieve our aim, we selected the co-treatment of chronic stress and LPS to induced an inflammatory process in rats. The effect of this co-treatment was evaluated through the expression of inflammatory markers and glial cell activation. LPS injection co-treated with unpredictable chronic mild stress resulted in the activation of microglial cell and astrocyte, expression of inflammatory markers and depressive behaviors. Treatment with apelin significantly attenuates the deleterious effects in these rats. Our results showed that apelin improved depressive phenotype and decreased the activation of glial cells in stress co-treatment group. The down-regulations of p-NF-κB and p-IKKß suggested that the effects are possibly mediated by inhibition of the NF-κB-mediated inflammatory response. These findings speculated that intracerebroventricular injection of apelin could be a therapeutic approach for the treatment of depression, and the antidepressant function of apelin may closely associated with its alleviation in neuroinflammation.


Assuntos
Antidepressivos/farmacologia , Apelina/farmacologia , Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Inflamação/tratamento farmacológico , Estresse Psicológico/psicologia , Animais , Antidepressivos/uso terapêutico , Apelina/uso terapêutico , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Depressão/metabolismo , Depressão/psicologia , Modelos Animais de Doenças , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/psicologia , Lipopolissacarídeos , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , NF-kappa B , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/metabolismo
17.
Exp Neurol ; 321: 113034, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31415741

RESUMO

Depression is the most common comorbidity among patients with epilepsy. Despite prior assumptions that antiepileptic drugs are to blame, more and more pathological studies have shown that latent neurological alterations associated with white matter injury and demyelination may underlie this link. However, whether disturbances in cerebral myelination contribute to the initiation of depression in epilepsy remains unclear. In the present study, we investigated the connection between demyelination disorders and the development of depression comorbidity in epilepsy. We first induced spontaneous recurrent epilepticus seizure (SRS) in young rats with pilocarpine. We then established depressive behaviors by recurrent forced swimming test and evaluate the depression state by sucrose preference test. The ratio of depression comorbidity in SRS rats was then calculated. Next, myelination in SRS-Depressed (SRS-D) rats was explored via PCR, western blotting, and immunohistochemistry for the key myelin promotion factor, Olig2 and inhibition factor, LINGO-1. Finally, in situ RNA hybridization of NCX3, one of the dominant Ca2+ extrusion proteins in oligodendrocytes (OLs) was performed to explore whether Ca2+ homeostasis of OLs was disturbed in epilepsy-induced hypoxic conditions and involved in the epilepsy-depression comorbidity. Our results revealed that one-quarter of the SRS rats displayed typical depressive behaviors, which were defined as SRS-D rats. In SRS-D rats, severe demyelination was also observed, accompanied with reduced expression of MBP, Olig2, and NCX3 and increased expression of LINGO-1 in the cingulate gyrus. In SRS-Non depressed rats, no significant changes were found from the control animals. This work provides new insights into the demyelination in epilepsy-depression comorbidity, which involves dysregulation of Olig2/LINGO-1 and disturbance of Ca2+ homeostasis.


Assuntos
Cálcio/metabolismo , Doenças Desmielinizantes/patologia , Depressão/metabolismo , Estado Epiléptico/patologia , Animais , Doença Crônica , Doenças Desmielinizantes/etiologia , Doenças Desmielinizantes/metabolismo , Depressão/etiologia , Depressão/patologia , Modelos Animais de Doenças , Homeostase , Masculino , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Fator de Transcrição 2 de Oligodendrócitos/metabolismo , Ratos , Ratos Sprague-Dawley , Estado Epiléptico/complicações , Estado Epiléptico/metabolismo
18.
J Nutr Sci Vitaminol (Tokyo) ; 65(3): 251-257, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257265

RESUMO

Collagen is the most abundant protein in animals. Collagen hydrolysate has been found to have multiple functions in the skin, bones, joints, muscles, and blood vessels. Recently, it has been reported that the low molecular weight fraction of collagen hydrolysate exhibited anxiolytic activity, suggesting that collagen peptides affect brain functions. In the present study, we found that oral administration of ginger-degraded collagen hydrolysate (GDCH) significantly decreased depression-like behavior in a forced swim test, suggesting that GDCH exhibited antidepressant activity in mice. The antidepressant activity of GDCH was abolished by pre-treatment with an antagonist of the dopamine receptor, but not treatment with a serotonin receptor antagonist. GDCH significantly increased gene expression of glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) in the hippocampus, molecules that affect the differentiation and survival of neurons, relative to that in the control condition. Meanwhile, there were no changes in the gene expression of brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3, major factors related to depression-like behavior. We also found that GDCH exhibited antidepressant activity in corticosterone-administered mice in a model of stress. In addition, GDCH increased GDNF and CNTF expression in the stressed condition, suggesting that mechanisms of the antidepressant activity of GDCH were the same in unstressed and stressed conditions. These results imply that GDCH exhibits antidepressant activity in unstressed and stressed conditions in mice. The upregulation of neurotrophic genes in the hippocampus may contribute to the reduction of depression-like behavior via a dopamine signal pathway modulated by GDCH.


Assuntos
Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Colágeno/farmacologia , Gengibre , Extratos Vegetais/farmacologia , Animais , Linhagem Celular , Depressão/metabolismo , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos , Fatores de Crescimento Neural/análise , Fatores de Crescimento Neural/metabolismo , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Estresse Psicológico/metabolismo
19.
Biol Pharm Bull ; 42(7): 1146-1154, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257291

RESUMO

Helicid (4-formylphenyl-O-ß-D-allopyranoside), an active component found in seeds from the Chinese herb Helicia nilagirica, has been reported to exert sedative, analgesic, hypnotic and antidepressant effects. The present study was designed to evaluate the antidepressant, learning and cognitive improvement effects of helicid in a chronic unpredictable mild stress (CUMS) model of depression in rats and to explore cAMP/protein kinase A (PKA)/cAMP response element-binding (CREB) signaling pathway. Sprague-Dawley rats were randomly assigned to six groups (n = 10): control; CUMS; CUMS + fluoxetine (5 mg/kg) and CUMS + helicid at 8, 16 and 32 mg/kg. All rats were subjected to 12 weeks of CUMS protocols and drug administration during the last 6 weeks of CUMS. Our results showed that helicid, at a dose of 32 mg/kg, significantly reversed decreases in body weight and sucrose consumption, increased the distance and number of crossings in the open-field test (OFT), reduced immobility times in the forced swimming test (FST) and improved spatial memory in the Morris water maze (MWM); all of these effects had been induced by CUMS paradigm. Immunohistochemistry showed that administration of helicid could promoted the proliferation of neurons in the hippocampal CA1 and dentate gyrus (DG) regions. CUMS rats treated with helicid had dramatically decreased protein levels of serotonin transporters (SERTs). In addition, CUMS resulted in a significant reduction in the expression of cAMP, PKA C-α and p-CREB, each of which were partially attenuated by helicid administration. These results indicated that helicid could improve depressive behaviors, learning and cognitive deficits and increase hippocampal neurogenesis, which may be mediated by the regulation of SERTs, activation of the cAMP/PKA/CREB signaling pathway and upregulation of p-CREB levels in hippocampal.


Assuntos
Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Benzaldeídos/farmacologia , Benzaldeídos/uso terapêutico , Depressão/tratamento farmacológico , Estresse Psicológico/tratamento farmacológico , Animais , Cognição/efeitos dos fármacos , AMP Cíclico/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Depressão/metabolismo , Depressão/psicologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiologia , Aprendizagem/efeitos dos fármacos , Masculino , Neurogênese/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia
20.
Food Funct ; 10(8): 4649-4660, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31292598

RESUMO

Metabolic disturbances, including lipid metabolism, bone metabolism, and glycometabolism, are common in depression. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), which are reported to possess antidepressant effect, have also been shown to regulate metabolism. To further clarify the potential link between ω-3 PUFAs and stress-induced metabolic disturbances, metabolic-related parameters including body weight, visceral fat, fatty acid composition and serum parameters, such as serum lipids, free fatty acid (FFA), glucose (GLU), calcium and phosphorus in rats were measured. Moreover, hepatic insulin induced gene (INSIG)/sterol regulatory element binding protein (SREBP) pathway was also investigated. After 5 weeks of chronic unpredicted mild stress (CUMS) administration, rats were induced to a depressive-like state and exhibited decreased serum high-density lipoprotein (HDL-c), body weight and visceral fat, accompanied by altered C18:2n6c and ω-3/ω-6 PUFAs. Supplement of ω-3 PUFAs showed robust antidepressant effects and has beneficial effects on lipid profile. On the contrary, ω-3 PUFAs deficiency induced the visceral fat accumulation and decreased the serum calcium and phosphorus in stressed rats. Additionally, CUMS significantly increased hepatic expressions of SREBP-cleavage activating protein (SCAP)/SREBP-1 and decreased the expression of INSIG-1. This disturbance of SREBPs system is aggravated by ω-3 PUFAs deficiency and alleviated by ω-3 PUFAs supplementation. This study discloses the novel findings that ω-3 PUFAs deficiency will exacerbate the metabolic disturbances in stressed rats. Furthermore, supplementation of ω-3 PUFAs on individuals with a high risk of depression might be an effective way to prevent metabolic disorders accompanied by depression with the involvement of INSIG/SREBP pathway.


Assuntos
Antidepressivos/administração & dosagem , Depressão/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Animais , Depressão/tratamento farmacológico , Depressão/genética , Depressão/psicologia , Suplementos Nutricionais/análise , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Ratos , Ratos Sprague-Dawley , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Estresse Psicológico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA