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1.
Brain Res ; 1835: 148930, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38604556

RESUMO

The anxiety caused by morphine protracted abstinence is considered to be an important factor contributes to drug-seeking and relapse. Endoplasmic reticulum (ER) stress plays important roles in many kinds of mental disorders including drug addiction and anxiety, but it is unclear whether ER stress is involved in anxiety-like behaviors induced by morphine withdrawal. In this study, by using behavioral test, western blot, immunofluorescence, electron transmission microscope, we found that: (1) Inhibition of endoplasmic reticulum stress by 4-Phenylbutyric acid (4-PBA) could attenuate anxiety-like behaviors induced by morphine withdrawal. (2) The endoplasmic reticulum stress-related proteins in the lateral habenula (LHb) but not in the nucleus accumbens (NAc), ventral pallidum (VP), basolateral amygdala (BLA) and CA1 of hippocampus was upregulated by morphine withdrawal, upregulation of endoplasmic reticulum stress-related proteins in the lateral habenula induced by morphine withdrawal was inhibited by 4-PBA. (3) Endoplasmic reticulum stress-related protein CHOP and eIF2α were expressed in neurons but not in microglia in the LHb. (4) Morphine withdrawal induced neuronal morphological change in the LHb, which was attenuated by 4-PBA.


Assuntos
Ansiedade , Estresse do Retículo Endoplasmático , Morfina , Síndrome de Abstinência a Substâncias , Animais , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/fisiologia , Masculino , Morfina/farmacologia , Ansiedade/metabolismo , Ansiedade/tratamento farmacológico , Síndrome de Abstinência a Substâncias/metabolismo , Camundongos , Fenilbutiratos/farmacologia , Dependência de Morfina/metabolismo , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Camundongos Endogâmicos C57BL
2.
Adv Mater ; 35(39): e2304069, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37485908

RESUMO

Mechanistic studies of the morphology of lead halide perovskite nanocrystals (LHP-NCs) are hampered by a lack of generalizable suitable synthetic strategies and ligand systems. Here, the synthesis of zwitterionic CsPbBr3 NCs is presented with controlled anisotropy using a proposed "surface-selective ligand pairs" strategy. Such a strategy provides a platform to systematically study the binding affinity of capping ligand pairs and the resulting LHP morphologies. By using zwitterionic ligands (ZwL) with varying structures, majority ZwL-capped LHP NCs with controlled morphology are obtained, including anisotropic nanoplatelets and nanorods, for the first time. Combining experiments with density functional theory calculations, factors that govern the ligand binding on the different surface facets of LHP-NCs are revealed, including the steric bulkiness of the ligand, the number of binding sites, and the charge distance between binding moieties. This study provides guidance for the further exploration of anisotropic LHP-NCs.

3.
Adv Mater ; 35(45): e2304168, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37463679

RESUMO

Chemical bath deposition (CBD) is widely used to deposit tin oxide (SnOx ) as an electron-transport layer in perovskite solar cells (PSCs). The conventional recipe uses thioglycolic acid (TGA) to facilitate attachments of SnOx particles onto the substrate. However, nonvolatile TGA is reported to harm the operational stability of PSCs. In this work, a volatile oxalic acid (OA) is introduced as an alternative to TGA. OA, a dicarboxylic acid, functions as a chemical linker for the nucleation and attachment of particles to the substrate in the chemical bath. Moreover, OA can be readily removed through thermal annealing followed by a mild H2 O2 treatment, as shown by FTIR measurements. Synergistically, the mild H2 O2 treatment selectively oxidizes the surface of the SnOx layer, minimizing nonradiative interface carrier recombination. EELS (electron-energy-loss spectroscopy) confirms that the SnOx surface is dominated by Sn4+ , while the bulk is a mixture of Sn2+ and Sn4+ . This rational design of a CBD SnOx layer leads to devices with T85 ≈1500 h, a significant improvement over the TGA-based device with T80 ≈250 h. The champion device reached a power conversion efficiency of 24.6%. This work offers a rationale for optimizing the complex parameter space of CBD SnOx to achieve efficient and stable PSCs.

5.
Psychoneuroendocrinology ; 151: 106080, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36931057

RESUMO

One negative emotional state from morphine protracted abstinence is anxiety which can drive craving and relapse risk in opioid addicts. Although the orexinergic system has been reported to be important in mediating emotion processing and addiction, the role of orexinergic system in anxiety from drug protracted abstinence remains elusive. In this study, by using behavioral test, western blot, electrophysiology and virus-mediated regulation of orexin receptor 1 (OX1R), we found that: (1) Intraperitoneal and intra-VTA administration of a selective OX1R antagonist SB334867 alleviated anxiety-like behaviors in open field test (OFT) but not in elevated plus maze test (EPM) in morphine protracted abstinent male mice. (2) OX1R expression in the VTA was upregulated by morphine withdrawal. (3) Virus-mediated knockdown of OX1R in the VTA prevented morphine abstinence-induced anxiety-like behaviors and virus-mediated overexpression of OX1R in the VTA was sufficient to produce anxiety-like behaviors in male mice. (4) The VTA neuronal activity was increased significantly induced by morphine protracted abstinence, which was mediated by OX1R. (5) OX1R was widely distributed in the neuronal soma and processes of dopaminergic and non-dopaminergic neurons in the VTA. The findings revealed that the OX1R mediates morphine abstinence-induced anxiety-like behaviors and the VTA plays a critical role in this effect.


Assuntos
Ansiedade , Morfina , Camundongos , Masculino , Animais , Morfina/farmacologia , Morfina/metabolismo , Receptores de Orexina/metabolismo , Ansiedade/metabolismo , Transtornos de Ansiedade/metabolismo , Neurônios/metabolismo
6.
Food Chem ; 416: 135856, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36898338

RESUMO

In this work, a highly sensitive method for aflatoxin B1 (AFB1) detection was developed based on a peroxidase-like spatial network structure. The specific antibody and antigen of AFB1 were coated on a histidine-modified Fe3O4 nanozyme to form the capture/detection probes. Based on the competition/affinity effect, the spatial network structure was constructed by the probes, which could be rapidly (8 s) separated by a magnetic three-phase single-drop microextraction process. In this single-drop microreactor, the network structure was applied to catalyze a colorimetric 3,3',5,5'-tetramethylbenzidine oxidation reaction for AFB1 detection. The signal was amplified significantly due to the strong peroxidase-like ability of the spatial network structure and the enrichment effect of the microextraction. Thus, a low detection limit (0.034 pg/mL) was achieved. The matrix effect of real sample can be eliminated by the extraction approach, and the practicability of this method was proved by agricultural product samples analysis.


Assuntos
Técnicas Biossensoriais , Peroxidase , Contaminação de Alimentos/análise , Aflatoxina B1/análise , Peroxidases , Corantes/análise , Fenômenos Magnéticos , Limite de Detecção , Técnicas Biossensoriais/métodos
7.
Ecotoxicol Environ Saf ; 248: 114294, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36402075

RESUMO

Biochar provides a suitable microenvironment for the growth of microorganisms. It may directly or indirectly affect changes in the population of microorganisms, thus affecting heavy metal bioavailability. This study aims to explore the effects of microbiological inoculation with and without biochar on microorganisms and on the bioavailability of heavy metals during pig manure composting. Three composting experiments were conducted under various conditions including no treatment (CK), only microbiological inoculation (TA), and integration with biochar (TB). Compared with raw materials before compost, TA reduced the bioavailability of Cu by 25.1%, Zn by 25.64%, and both Pb and Cr by 1.75%. TB reduced the bioavailability of Cu by 35.38%, Zn by 19.34%, Pb by 0.81%, and Cr by 3.9%. Furthermore, correlation analysis demonstrated that Debaryomyces were the primary fungi, possibly controlling the passivation of Cr. Bacillus, Fusarium, Pseudogracilibacillus, Sinibacillus, and Botryotrichum were the primary bacteria and fungi potentially governing the passivation of Zn, Lastly, Debaryomyces and Penicillium were the primary bacteria and fungi potentially controlling the passivation of Pb and Cu, respectively. Overall, we demonstrated that pig manure added to the microbial inoculum and biochar effectively reduced the bioavailability of heavy metals, thereby offering an applicable technology for reducing heavy metal contamination during pig manure composting.


Assuntos
Bacillaceae , Compostagem , Metais Pesados , Suínos , Animais , Esterco , Disponibilidade Biológica , Chumbo
8.
Front Public Health ; 10: 946439, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35991008

RESUMO

Background: Previous studies have found that exposure to heavy metals increased the incidence of congenital heart defects (CHDs). However, there is a paucity of information about the connection between exposure to titanium and CHDs. This study sought to examine the relationship between prenatal titanium exposure and the risk of CHDs in offspring. Methods: We looked back on a birth cohort study that was carried out in our hospital between 2010 and 2012. The associations between titanium exposure and the risk of CHDs were analyzed by using logistic regression analysis to investigate titanium concentrations in maternal whole blood and fetal umbilical cord blood. Results: A total of 97 case groups and 194 control groups were included for a nested case-control study. The [P50 (P25, P75)] of titanium were 371.91 (188.85, 659.15) µg/L and 370.43 (264.86, 459.76) µg/L in serum titanium levels in pregnant women and in umbilical cord serum titanium content in the CHDs group, respectively. There was a moderate positive correlation between the concentration of titanium in pregnant women's blood and that in umbilical cord blood. A higher concentrations of maternal blood titanium level was associated with a greater risk of CHDs (OR 2.706, 95% CI 1.547-4.734), the multiple CHDs (OR 2.382, 95% CI 1.219-4.655), atrial septal defects (OR 2.367, 95% CI 1.215-4.609), and patent ductus arteriosus (OR 2.412, 95% CI 1.336-4.357). Dramatically higher concentrations of umbilical cord blood levels had an increased risk of CHDs and different heart defects. Conclusion: Titanium can cross the placental barrier and the occurrence of CHDs may be related to titanium exposure.


Assuntos
Cardiopatias Congênitas , Metais Pesados , Estudos de Casos e Controles , China/epidemiologia , Estudos de Coortes , Feminino , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/etiologia , Humanos , Exposição Materna/efeitos adversos , Metais Pesados/efeitos adversos , Placenta , Gravidez , Titânio/efeitos adversos
9.
Front Microbiol ; 12: 746718, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899633

RESUMO

This study evaluated the effects of thermophilic microbiological inoculation alone (TA) and integrated with biochar (TB) on the physicochemical characteristics and bacterial communities in pig manure (PM) composting with wheat straw. Both TA and TB accelerated the rate of temperature increase during the PM composting. TA significantly reduced total nitrogen loss by 18.03% as opposed to TB which significantly accelerated total organic carbon degradation by 12.21% compared with the control. Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria were the major phyla in composting. Variation of the relative abundance of genera depended on the composting period and treatment. The genera Lactobacillus (26.88-46.71%) and Clostridium_sensu_stricto (9.03-31.69%) occupied a superior position in the temperature rise stage, and Bacillus (30.90-36.19%) was outstanding in the cooling stage. Temperature, total nitrogen (TN), and ammonium nitrogen significantly influenced the bacterial phyla composition. TN, water content, and nitrite nitrogen were the main drivers of the bacterial community genera. Furthermore, our results demonstrated that microbiological consortia were resistant to high temperatures and could fix nitrogen for enriched Pseudomonas; however, when interacted with biochar, total organic carbon (TOC) degradation was accelerated for higher bacterial richness and diversity as well as overrepresented Corynebacterium.

10.
Adv Mater ; 33(27): e2100854, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34048075

RESUMO

Photon upconversion via triplet-triplet annihilation (TTA) has promise for overcoming the Shockley-Queisser limit for single-junction solar cells by allowing the utilization of sub-bandgap photons. Recently, bulk perovskites have been employed as sensitizers in solid-state upconversion devices to circumvent poor exciton diffusion in previous nanocrystal (NC)-sensitized devices. However, an in-depth understanding of the underlying photophysics of perovskite-sensitized triplet generation is still lacking due to the difficulty of precisely controlling interfacial properties of fully solution-processed devices. In this study, interfacial properties of upconversion devices are adjusted by a mild surface solvent treatment, specifically altering perovskite surface properties without perturbing the bulk perovskite. Thermal evaporation of the annihilator precludes further solvent contamination. Counterintuitively, devices with more interfacial traps show brighter upconversion. Approximately an order of magnitude difference in upconversion brightness is observed across different interfacial solvent treatments. Sequential charge transfer and interfacial trap-assisted triplet sensitization are demonstrated by comparing upconversion performance, transient photoluminescence dynamics, and magnetic field dependence of the devices. Incomplete triplet conversion from transferred charges and consequent triplet-charge annihilation (TCA) are also observed. The observations highlight the importance of interfacial control and provide guidance for further design and optimization of upconversion devices using perovskites or other semiconductors as sensitizers.

11.
Nature ; 590(7847): 587-593, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33627807

RESUMO

Metal halide perovskite solar cells (PSCs) are an emerging photovoltaic technology with the potential to disrupt the mature silicon solar cell market. Great improvements in device performance over the past few years, thanks to the development of fabrication protocols1-3, chemical compositions4,5 and phase stabilization methods6-10, have made PSCs one of the most efficient and low-cost solution-processable photovoltaic technologies. However, the light-harvesting performance of these devices is still limited by excessive charge carrier recombination. Despite much effort, the performance of the best-performing PSCs is capped by relatively low fill factors and high open-circuit voltage deficits (the radiative open-circuit voltage limit minus the high open-circuit voltage)11. Improvements in charge carrier management, which is closely tied to the fill factor and the open-circuit voltage, thus provide a path towards increasing the device performance of PSCs, and reaching their theoretical efficiency limit12. Here we report a holistic approach to improving the performance of PSCs through enhanced charge carrier management. First, we develop an electron transport layer with an ideal film coverage, thickness and composition by tuning the chemical bath deposition of tin dioxide (SnO2). Second, we decouple the passivation strategy between the bulk and the interface, leading to improved properties, while minimizing the bandgap penalty. In forward bias, our devices exhibit an electroluminescence external quantum efficiency of up to 17.2 per cent and an electroluminescence energy conversion efficiency of up to 21.6 per cent. As solar cells, they achieve a certified power conversion efficiency of 25.2 per cent, corresponding to 80.5 per cent of the thermodynamic limit of its bandgap.

12.
Sci Total Environ ; 648: 1097-1104, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30340256

RESUMO

China has been undergoing dramatic land-use change since the1980s. More arable lands have been converted to orchards to produce high-value fruits. There is an urgent need to assess the effects of these land-use changes on soil erosion and nutrient loss in the country. In this study, the Revised Universal Soil Loss Equation model, geographical information systems, and, remote sensing data were used to evaluate the effects of land-use change on soil erosion and nutrient loss in the Yujiahe Catchment, where a significant portion of the arable land that grew wheat and maize between1957 and 1989 was converted to kiwifruit orchards between 1990 and 2013. The total soil erosion from the catchment during 1957-2013 was in line with the sediments in the reservoir at the catchment outlet. Arable land was the major source of soil erosion and its erosion intensity was approximately ten times that of the orchards. The land-use change from arable land to orchard land since 1990 has reduced soil erosion intensity from severe to moderate. The arable land covering 28% of the catchment contributed to 81.3% of total organic matter loss and 80.4% of total nitrogen loss. However, the loss of available phosphorus mainly occurred in the orchards, representing 66.7% of the available phosphorus loss in the catchment. The soil erosion intensity of the arable land was highly sensitive to the land slope. We concluded that land use change from arable land to orchard land reduced soil erosion and increased the risk of nutrient loss from the catchment.

13.
J Mol Neurosci ; 59(4): 493-503, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27129498

RESUMO

Inflammation plays a pivotal role in the pathogenesis of many diseases in the central nervous system. Caudate nucleus (CN), the largest nucleus in the brain, is also implicated in many neurological disorders. 2-Arachidonoylglycerol (2-AG), the most abundant endogenous cannabinoid, has been shown to exhibit neuroprotective effects through its anti-inflammatory action from some proinflammatory stimuli. However, the neuroprotective mechanism of 2-AG is complex and has not been fully understood. A-type K(+) channels critically regulate neuronal excitability and have been demonstrated to be associated with some nervous system diseases. The aim of this study was to explore whether A-type K(+) channels were involved in neurotoxicity of lipopolysaccharides (LPS) and the neuroprotective mechanism of 2-AG in CN neurons. Whole cell patch clamp recording was used to investigate the influence of LPS on the function of A-type K(+) channels and its modulation by 2-AG in primary cultured rat CN neurons. Our findings showed that in cultured CN neurons, LPS significantly decreased the A-type potassium currents (I A) in a voltage-insensitive way. The further data demonstrated that an elevation of 2-AG levels by directly applying exogenous 2-AG or inhibiting monoacylglycerol lipase (MAGL) to prevent 2-AG hydrolysis was capable of suppressing the LPS-induced inhibition of IA and the action of 2-AG is mediated through CB1 receptor-dependant way. The study provides a better understanding of inflammation-related neurological disorders and suggests the therapeutic potential for 2-AG for the treatment of these diseases.


Assuntos
Ácidos Araquidônicos/farmacologia , Agonistas de Receptores de Canabinoides/farmacologia , Núcleo Caudado/metabolismo , Endocanabinoides/farmacologia , Glicerídeos/farmacologia , Neurônios/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Potenciais de Ação , Animais , Núcleo Caudado/citologia , Núcleo Caudado/efeitos dos fármacos , Células Cultivadas , Lipopolissacarídeos/farmacologia , Monoacilglicerol Lipases/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Ratos , Ratos Sprague-Dawley , Receptor CB1 de Canabinoide/agonistas
14.
Front Psychol ; 7: 641, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27199866

RESUMO

Using testing and questionnaire methods, this study investigated the relationships among openness to experience, intelligence and creative thinking. This study focused on the moderating effects of openness to experience on the relationship between intelligence and creative thinking in a sample of 831 primary school students in China. The findings showed significant positive relationships among openness to experience, intelligence and creative thinking. In relation to the focus of this study, openness to experience moderated the relationship between intelligence and creative thinking. However, the correlation between openness to experience and creative thinking was stronger for urban children than for rural children, and the moderating effect existed only in urban settings.

15.
Ying Yong Sheng Tai Xue Bao ; 26(7): 2203-12, 2015 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-26710651

RESUMO

Nitrogen use efficiency (NUE) has received worldwide concern in the sphere of agronomic science and environmental science, and it is fundamentally important for evaluating N utilization status and optimizing N fertilization management in cultivated lands. In recent years, in consideration of low values and great variations of NUE in China' s cultivated lands, some scholars have discussed on the traditional concept and calculating method of NUE, and also have proposed some substituted NUE calculating methods. In this paper, we summarized some disadvantages of both conventional concept and calculating method of NUE, i.e. the subtraction method and the 15N labeling method. Furthermore, we particularly introduced several substituted NUE calculation methods and discussed research directions in the future. In summary, we strongly suggested the establishment of a comprehensive evaluation index system of N utilization in good accordance with the current agricultural production status in China, based on a correct understanding of the dialectical relationships among N application rate, crop yield, N utilization and N loss.


Assuntos
Agricultura/métodos , Fertilizantes , Nitrogênio/análise , China
16.
Ying Yong Sheng Tai Xue Bao ; 26(4): 1179-85, 2015 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-26259461

RESUMO

In order to ascertain the effects of potassium fertilizer application periods on apple production, we conducted a field experiment and analyzed the differences in apple yield, fruit quality, potassium fertilizer use efficiency, and nutrient concentrations in leaves and fruits among treatments with differences in timing of potassium application. The results indicated that, compared with no potassium-applied treatment (CK), all potassium fertilizer application treatments significantly increased the apple yield by 4.3%-33.2%, meanwhile, it also obviously improved the fruit quality. In comparison with the application of 100% potassium fertilizer as a base, the application of 50% or 100% of potassium fertilizer at the fruit enlargement stage (the remaining 50% applied as a base or after flowering) significantly increased the apple yield by 20.5% - 27.7% and improved the fruit quality. Compared with the application 100% potassium fertilizer at the stage of fruit enlargement, the evenly split application as base flowering stage and at the fruit enlargement: stage not only contributed to a higher yield, better quality and higher potassium use efficiency, but also maintained a relatively stable potassium concentration level in leaves. However, the split potassium fertilizer application at the flowering and fruit enlargement stages resulted in the significant decrease in concentration of calcium in fruit, which would be negative to fruit quality. In conclusion, our research suggested that evenly split application of potassium fertilizer as a base and at the fruit enlargement stage was the suitable period for apple production in Fuji apple orchards in this region.


Assuntos
Agricultura/métodos , Fertilizantes , Frutas , Malus/crescimento & desenvolvimento , Potássio/química , Folhas de Planta/química
17.
J Mol Neurosci ; 57(4): 477-85, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26179279

RESUMO

Homocysteine (Hcy) is an important risk factor for Alzheimer's disease (AD) and other neurodegenerative diseases. Caudate nucleus (CN), the largest nucleus in the brain, is also implicated in many neurological disorders. 2-Arachidonoylglycerol (2-AG), the most abundant endogenous cannabinoid, has been shown to exhibit neuroprotective effects from many stimuli in the central nervous system (CNS). Furthermore, it has been reported that voltage-gated sodium channels (VGSCs) are the common targets of many neuronal damages and drugs. However, it is still not clear whether VGSCs are involved in the neurotoxicity of Hcy and the neuroprotective effect of 2-AG in CN neurons. In the present study, whole-cell patch clamp recording was used to invest the action of Hcy on sodium currents in primary cultured rat CN neurons and its modulation by 2-AG. The results showed that in cultured CN neurons, pathological concentration of Hcy (100 µM) significantly increased the voltage-gated sodium currents (I(Na)) and produced a hyperpolarizing shift in the activation-voltage curve of I(Na). The further data demonstrated 2-AG is capable of suppressing elevation of Hcy-induced increase in I(Na) and hyperpolarizing shift of activation curves most partly through CB1 receptor-dependent way. Our study provides a better understanding of Hcy-associated neurological disorders and suggests the therapeutic potential for 2-AG for the treatment of these diseases.


Assuntos
Ácidos Araquidônicos/farmacologia , Agonistas de Receptores de Canabinoides/farmacologia , Núcleo Caudado/fisiologia , Endocanabinoides/farmacologia , Glicerídeos/farmacologia , Homocisteína/toxicidade , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Canais de Sódio Disparados por Voltagem/metabolismo , Potenciais de Ação , Animais , Núcleo Caudado/citologia , Núcleo Caudado/efeitos dos fármacos , Células Cultivadas , Neurônios/fisiologia , Ratos , Ratos Sprague-Dawley
18.
Life Sci ; 138: 64-71, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25818189

RESUMO

AIMS: URB602 is a selective inhibitor of monoacylglycerol lipase (MAGL), a serine hydrolase involved in the biological deactivation of the endocannabinoid 2-arachidonoyl glycerol (2-AG). It has been described that URB602 significantly enhances depolarization-induced increases in 2-AG. A high level of homocysteine (Hcy) is a modifiable risk factor for developing Alzheimer's disease (AD). The aim of this study was to investigate the protective effects of URB602 on Hcy-induced impairments underlying its cellular and molecular mechanism in primary cultured caudate nucleus (CN) neurons. MAIN METHODS: The expressions of cyclooxygenase-2 (COX-2), ERK1/2, NF-κB and IκB-α as well as cleaved caspase-3 and p-Bcl-2 in Hcy-, URB602 or SR1 (a selective inhibitor of CB1 receptor)-treated primary cultured neurons in CN were measured by immunoblotting technique and neurotoxicity assays were performed by using Hoechst staining. KEY FINDINGS: The MAGL inhibitor URB602 exerted a neuroprotective effect on Hcy-induced impairment through suppression of cyclooxygenase-2 (COX-2) elevation and ERK1/2 and NF-κB phosphorylation as well as suppressions of IκB-α degradation in a CB1 receptor-dependent way. Moreover, anti-neuronal impairments of URB602 were mediated by modulating down-regulation of cleaved caspase-3 expression and up-regulation of p-Bcl-2 expression in a CB1 receptor-dependent manner in primary cultured CN neurons. SIGNIFICANCE: These data suggest that the MAGL inhibitor is a promising therapeutic target for some neurodegenerative disorders, such as AD, via the COX-2 signaling pathway.


Assuntos
Compostos de Bifenilo/farmacologia , Núcleo Caudado/efeitos dos fármacos , Ciclo-Oxigenase 2/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Homocisteína/toxicidade , Monoacilglicerol Lipases/antagonistas & inibidores , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Receptor CB1 de Canabinoide/efeitos dos fármacos
19.
J Mol Neurosci ; 55(2): 500-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25007951

RESUMO

Homocysteine (Hcy) is a high risk factor for Alzheimer's disease (AD). Caudate nucleus (CN), the major component of basal ganglia in the brain, is also involved in many neurological disorders. 2-Arachidonoylglycerol (2-AG), the true natural ligand for cannabinoid type-1 (CB1) receptors and the most abundant endogenous cannabinoid, has been shown to exhibit neuroprotective effects through its anti-inflammatory action from proinflammatory stimuli in the hippocampus and CN. However, it is still not well understood whether that 2-AG is also able to protect CN neurons from Hcy harmful insults. In the present work, we explored that 2-AG significantly protects CN neurons in culture against Hcy-induced response. 2-AG is capable of inhibiting elevation of Hcy-induced cyclooxygenase-2 expression associated with nuclear factor-kappaB/p38MAPK/ERK1/2 signaling pathway through CB1 receptors-dependent way in primary cultured CN neurons. Our study reveals the therapeutic potential for 2-AG for the treatment of neurodegenerative diseases, such as AD.


Assuntos
Ácidos Araquidônicos/farmacologia , Agonistas de Receptores de Canabinoides/farmacologia , Núcleo Caudado/metabolismo , Endocanabinoides/farmacologia , Glicerídeos/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Receptor CB1 de Canabinoide/metabolismo , Animais , Núcleo Caudado/citologia , Células Cultivadas , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Homocisteína/toxicidade , Sistema de Sinalização das MAP Quinases , NF-kappa B/metabolismo , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor CB1 de Canabinoide/agonistas
20.
J Mol Neurosci ; 54(1): 49-58, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24510751

RESUMO

Inflammation plays a pivotal role in the pathogenesis of many diseases in the central nervous system. Caudate nucleus (CN), the largest nucleus in the brain, is also implicated in many neurological disorders. 2-Arachidonoylglycerol (2-AG), the most abundant endogenous cannabinoid and the true natural ligand for CB1 receptors, has been shown to exhibit neuroprotective effects through its anti-inflammatory action from proinflammatory stimuli in hippocampus. However, it is still not clear whether 2-AG is also able to protect CN neurons from proinflammation stimuli. In the present study, we discovered that 2-AG significantly protects CN neurons in culture against lipopolysaccharide (LPS)-induced inflammatory response. 2-AG is capable of suppressing elevation of LPS-induced cyclooxygenase-2 expression associated with ERK/p38MAPK/NF-κB signaling pathway in CB1 receptor-dependant manner in primary cultured CN neurons. Moreover, 2-AG inhibits LPS-induced increase in voltage-gated sodium channel currents and hyperpolarizing shift of activation curves through CB1 receptor-dependant pathway. Our study suggests the therapeutic potential of 2-AG for the treatment of some inflammation-induced neurological disorders and pain.


Assuntos
Ácidos Araquidônicos/farmacologia , Agonistas de Receptores de Canabinoides/farmacologia , Núcleo Caudado/efeitos dos fármacos , Endocanabinoides/farmacologia , Glicerídeos/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Potenciais de Ação , Animais , Núcleo Caudado/citologia , Núcleo Caudado/metabolismo , Células Cultivadas , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases , Neurônios/metabolismo , Neurônios/fisiologia , Ratos , Ratos Sprague-Dawley , Canais de Sódio/metabolismo
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