RESUMO
Depression is increasingly recognized as an inflammatory disease, with inflammatory crosstalk in the brain contributing its pathogenesis. Life stresses may up-regulate inflammatory processes and promote depression. Although cytokines are central to stress-related immune responses, their contribution to stress-induced depression remains unclear. Here, we used unpredictable chronic mild stress (UCMS) to induce depression-like behaviors in mice, as assessed through a suite of behavioral tests. C-X-C motif chemokine ligand 1 (CXCL1)-related molecular networks responsible for depression-like behaviors were assessed through intrahippocampal microinjection of lenti-CXCL1, the antidepressant fluoxetine, the C-X-C motif chemokine receptor 2 (CXCR2) inhibitor SB265610, and the glycogen synthase kinase-3ß (GSK3ß) inhibitor AR-A014418. Modulation of apoptosis-related pathways and neuronal plasticity were assessed via quantification of cleaved caspase-3, B-cell lymphoma 2-associated X protein, cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF) protein expression. CXCL1/CXCL2 expression was correlated with depression-like behaviors in response to chronic stress or antidepressant treatment in the UCMS depression model. Intrahippocampal microinjection of lenti-CXCL1 increased depression-like behaviors, activated GSK3ß, increased apoptosis pathways, suppressed CREB activation, and decreased BDNF. Administration of the selective GSK3ß inhibitor AR-A014418 abolished the effects of lenti-CXCL1, and the CXCR2 inhibitor SB265610 prevented chronic stress-induced depression-like behaviors, inhibited GSK3ß activity, blocked apoptosis pathways, and restored BDNF expression. The CXCL1/CXCR2 axis appears to play a critical role in stress-induced depression, and CXCR2 is a potential novel therapeutic target for patients with depression.-Chai, H.-H., Fu, X.-C., Ma, L., Sun, H.-T., Chen, G.-Z., Song, M.-Y., Chen, W.-X., Chen, Y.-S., Tan, M.-X., Guo, Y.-W., Li, S.-P. The chemokine CXCL1 and its receptor CXCR2 contribute to chronic stress-induced depression in mice.
Assuntos
Quimiocina CXCL1/metabolismo , Depressão/metabolismo , Receptores de Interleucina-8B/metabolismo , Animais , Antidepressivos de Segunda Geração/farmacologia , Apoptose , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Quimiocina CXCL1/genética , Depressão/etiologia , Depressão/genética , Fluoxetina/farmacologia , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Plasticidade Neuronal , Compostos de Fenilureia/farmacologia , Receptores de Interleucina-8B/genética , Estresse Psicológico/complicações , Tiazóis/farmacologia , Triazóis/farmacologia , Ureia/análogos & derivados , Ureia/farmacologiaRESUMO
Spermatogenesis is a complex regulatory process depending on a variety of hormones (such as FSH, LH, T, and 17beta estradiol), cytokines, and genes. Research on gene regulation in spermatogenesis has become a hot spot and revealed some spermato-genesis-related genes, such as AYZ, DAZ, YRRM, NOSTRIN, and so on. Reports are rarely seen on the role of CR16 in male reproduction, and its action mechanism in spermatogenesis is not yet clear. This article updates the role of CR16 in spermatogenesis in the male reproductive system from the perspective of Sertoli cells forming a blood-testis barrier.
Assuntos
Proteínas dos Microfilamentos , Espermatogênese , Animais , Barreira Hematotesticular , Humanos , Masculino , Células de Sertoli , Testículo/citologiaAssuntos
Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Estudantes de Medicina , beta-Lactamases/biossíntese , Farmacorresistência Bacteriana , Escherichia coli/enzimologia , Escherichia coli/isolamento & purificação , Fezes/microbiologia , Feminino , Humanos , Masculino , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: To evaluate the effects of paroxetine on protein kinase PKA, PKC and CaMKII activities in different brain regions in a rat model of depression. METHODS: Thirty-six adult male SD rats were randomized into 6 groups, including one control group (I) and 5 groups of depression model established by forcing the rats to swim for 4 weeks. The 5 depression groups received no treatment (II) or were treated with paroxetine at a single dose (III), for a week (IV), 2 weeks (V) or 4 weeks (VI). The radioactivity of PKA, PKC and CaMKII in the hippocampus and prefrontal cortex was quantitatively measured using a liquid scintillation counter. RESULTS: In the rat hippocampus, PKA and CaMKII activities were significantly lower in groups II, III, IV, and V than in groups I and VI (P<0.01 or P<0.05), but comparable between groups VI and I (P>0.05). PKC activity was significantly lower in group II than in group I (P<0.01), but showed no significant difference between the paroxetine-treated groups and group I (P>0.05). In the prefrontal cortex, the activity of PKA in groups I, II, III, and IV was similar (P>0.05), but all significantly lower than that in groups V and VI (P<0.01). PKC activity was significantly higher in groups II and III than that in group I and other paroxetine-treated groups (P<0.01), and similar between groups IV and I (P>0.05); groups V and VI had significantly lower PKC activity than group I (P<0.01). Group I had the highest CaMKII activity among the groups (P<0.01). CONCLUSION: Chronic administration of paroxetine can reverse chronic stress-induced inhibition of PKA, PKC and CaMKII activity in rat hippocampus, while the effects of paroxetine on the protein kinases can be more complex in prefrontal cortex.
Assuntos
Encéfalo/efeitos dos fármacos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Depressão/enzimologia , Paroxetina/farmacologia , Proteína Quinase C/metabolismo , Animais , Encéfalo/enzimologia , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Masculino , Distribuição Aleatória , RatosRESUMO
Three new compounds, ilexisochromane (1), ilex acid A (2), and ilex acid B (3), were isolated from the roots of Ilex pubescens. Their structures were elucidated using the combination of 1- and 2-D NMR and mass spectrometry analyses.
Assuntos
Benzopiranos/química , Caproatos/química , Ilex/química , Estrutura Molecular , Raízes de Plantas/químicaRESUMO
OBJECTIVE: To study the protective effects of orientin against myocardial ischemia and hypoxia in rats. METHODS: The protective effect of orientin against myocardial ischemia and hypoxia was observed in mice by recording their survival time under closed normobaric hypoxia and time of cardiac electric disappearance due to trachea clamping, in rabbits by evaluating arachidonic acid (AA)-induced blood platelet aggregation, in guinea pigs by measuring the coronal flow in the isolated heart and in SD rats with myocardial ischemia induced by pituitrin injection. RESULTS: Orientin (1, 2, 4 mg/kg) significantly prolonged the survival time of mice under closed normobaric hypoxia and the gasping duration induced by decapitation. Orientin at concentrations of 3, 10, and 30 micromol/L also inhibited AA-induced blood platelet aggregation in rabbits and increased coronal flow in the isolated heart of guinea pigs. At 0.75, 1.5, and 3.0 mg/kg, orientin significantly antagonized pituitrin-induced ECG changes. CONCLUSION: Orientin may offer protection against myocardial ischemia and hypoxia in animal models in dose-dependent fashions.
Assuntos
Flavonoides/farmacologia , Glucosídeos/farmacologia , Hipóxia/prevenção & controle , Isquemia Miocárdica/prevenção & controle , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eletrocardiografia , Feminino , Cobaias , Hipóxia/fisiopatologia , Masculino , Camundongos , Isquemia Miocárdica/fisiopatologia , Agregação Plaquetária/efeitos dos fármacos , Coelhos , Ratos , Taxa de SobrevidaRESUMO
In this paper we investigated the vascular activity and possible mechanism of Orientin, from bamboo leaves (Phyllostachys nigra), in isolated thoracic aortic rings from New Zealand rabbit. Among the four compounds, studied, only Orientin relaxed phenylephrine-induced contractions with an IC50 value of 2.28 microM in the endothelium intact and with an IC50 value around 7.27 microM in the endothelium removed aortic rings. The vasorelaxant effect of Orientin on endothelium-intact thoracic aortic rings was attenuated by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester, but not by indomethacin (a cyclooxygenase inhibitor), tetraethylammonium chloride (K+ channels inhibitor) or propranolol (beta-receptor inhibitor). Furthermore, Orientin inhibited norepinephrine (NE), CaCl2 and KCl-induced vasoconstriction concentration dependently in a non-competitive manner, and also reduced both the initial fast release and the sustained phases of phenylephrine-induced contractions. Orientin can stimulate NO production from endothelial cells. Orientin also increased cyclic guanosine 3,5-cyclic monophosphate (cGMP) levels without changes in adenosine-3',5'-cyclic phosphoric acid (cAMP) in rabbit aorta. The results showed that Orientin relaxed thoracic aortic rings by the nitric oxide-cGMP pathway, and in the vascular smooth muscle inhibited the contraction induced by the activation of receptor-operating and voltage-dependent Ca2+ channels. Cyclooxygenase pathway, potassium channels, beta-receptors and cAMP pathway, on the other hand, had no apparent roles. The inhibition of both intracellular Ca2+ release and extracellular Ca2+ influx may be one of the main vasorelaxant mechanisms of Orientin.