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1.
Psychol Rep ; : 332941241227161, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38211339

RESUMO

Given the current increases in the divorce rate and the number of single-parent families, the development of gender roles among children from single-parent families has received more and more attention. This study investigated how single parents influenced the formation of their children's gender roles and family-related factors that benefited the development of gender roles in single-parent children. Through in-depth interviews with 24 pairs of parents and children from single-parent families, we investigated single parents' and their children's cognition on gender roles, parents' parenting attitudes and behaviors during their children's gender role development, and communication and interaction between parents and children. Results showed intergenerational consistency in the gender role concepts of parents and their children in single-parent families. However, the children's gender role concepts were not completely and directly inherited from their parents, and could be affected by their subjective initiative. Additionally, single parenting did not necessarily negatively impact children's gender role development, which depends on their parent's parenting style. The study's limitations are discussed, and future directions for in-depth research are suggested.

2.
Medicine (Baltimore) ; 102(47): e35584, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38013353

RESUMO

Early maladaptive schemas (EMSs) may be closely related to nonsuicidal self-injury (NSSI). The present study aimed to discuss the relationship between EMS and a personal history of NSSI. This was a retrospective study. A total of 1339 Chinese college students between 16 and 29 years old were asked to complete a questionnaire survey regarding their personal history of NSSI and EMSs. 116 college students reported a history of NSSI (NSSI group), who differed significantly in terms of all EMS-related scores than non-NSSI group(n = 1223). Logistic regression analysis showed that the scores in the disconnection/rejection schema domain exhibited by subjects who were the only child in their family could help differentiate between college students with or without NSSI. The emotional deprivation schema was significantly associated with the lifetime frequency of NSSI behaviors; the vulnerability to harm or illness schema was significantly associated with the internal emotion regulation function and pain associated with NSSI; and the enmeshment/underdeveloped self schema was significantly associated with the addictive features of NSSI. The self-sacrifice schema was significantly associated with the external emotion regulation function of NSSI; the enmeshment/underdeveloped self schema was positively related with the sensation-seeking function of NSSI; and the abandonment/instability schema was negatively related the sensation-seeking function of NSSI. The disconnection/rejection schema domain was highly related with NSSI behaviors. EMS is significantly associated with the history, functions, addictive features, and severity of NSSI. Every EMS is worthy of further investigation and discussion with patients in the context of NSSI behaviors during clinical therapy.


Assuntos
Emoções , Comportamento Autodestrutivo , Criança , Humanos , Adolescente , Adulto Jovem , Adulto , Estudos Retrospectivos , Estudantes/psicologia , Inquéritos e Questionários , Comportamento Autodestrutivo/epidemiologia , Comportamento Autodestrutivo/psicologia
3.
Front Neurol ; 14: 1102837, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37064180

RESUMO

Introduction: The pedunculopontine nucleus (PPTg) is a vital interface between the basal ganglia and cerebellum, participating in modulation of the locomotion and muscle tone. Pathological changes of the PPTg have been reported in patients and animal models of dystonia, while its effect and mechanism on the phenotyping of dystonia is still unknown. Methods: In this study, a series of behavioral tests focusing on the specific deficits of dystonia were conducted for mice with bilateral and unilateral PPTg excitotoxic lesion, including the dystonia-like movements evaluation, different types of sensory-motor integrations, explorative behaviors and gait. In addition, neural dysfunctions including apoptosis, neuroinflammation, neurodegeneration and neural activation of PPTg-related motor areas in the basal ganglia, reticular formations and cerebellum were also explored. Results: Both bilateral and unilateral lesion of the PPTg elicited dystonia-like behaviors featured by the hyperactivity of the hindlimb flexors. Moreover, proprioceptive and auditory sensory-motor integrations were impaired in bilaterally lesioned mice, while no overt alterations were found for the tactile sensory-motor integration, explorative behaviors and gait. Similar but milder behavioral deficits were found in the unilaterally lesioned mice, with an effective compensation was observed for the auditory sensory-motor integration. Histologically, no neural loss, apoptosis, neuroinflammation and neurodegeneration were found in the substantia nigra pars compacta and caudate putamen (CPu) following PPTg lesion, while reduced neural activity was found in the dorsolateral part of the CPu and striatal indirect pathway-related structures including subthalamic nucleus, globus pallidus internus and substantia nigra pars reticular. Moreover, the neural activity was decreased for the reticular formations such as pontine reticular nucleus, parvicellular reticular nucleus and gigantocellular reticular nucleus, while deep cerebellar nuclei were spared. Conclusion: In conclusion, lesion of the PPTg could elicit dystonia-like behaviors through its effect on the balance of the striatal pathways and the reticular formations.

4.
Sci Total Environ ; 882: 163629, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37086994

RESUMO

Global warming and glacier retreat have significant impacts on the structure and function of natural ecosystems. However, little is known about how glacier retreat affects the long-term evolution of ecosystems at high-altitude regions. In this study, we explored the possible effects of glacier retreat on catchment vegetation and lake productivity in Lake Puma Yumco, southeastern Tibetan Plateau, based on detailed organic molecular compositions determined by an ultra-high-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), and combined with various sedimentary geochemical indicators. The glaciers in the catchment keep retreating since 1870 CE, as inferred from the multiple indices of total organic carbon content (TOC), total nitrogen content (TN), C/N ratios, and carbonate contents. Accompanying modern global warming and glacier shrinkage, the relative abundance of soil- and vegetation-derived large molecular compounds (e.g., vascular plant-derived polyphenols, highly unsaturated and phenolic compounds, and condensed aromatics) increased gradually in lake sediments, suggesting that ice-covered land was exposed under warming condition, and gradually revegetation occurred. Both increases in relative abundance of nitrogen-containing compounds (e.g., CHNO) and chlorophyll derivative contents in the lake sediments were observed since 1870 CE, suggesting that stronger catchment weathering and increasing terrestrial nutrient loads enhanced the downstream lake productivity after glacier retreat. Our results imply that continued global warming and alpine glacier retreat in the future may further promote vegetation expansion and increases in lake productivity on the Tibetan Plateau.

5.
Environ Res ; 227: 115753, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-36965811

RESUMO

Lake eutrophication seriously threatens water quality and human health. Under continuous global warming and intensified human activity, increasing attention is being paid to how lake trophic status responds to climate change and anthropogenic impacts. Based on the sedimentary organic matter (SOM) molecular composition determined by the Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) technology, and combined with the SOM stable nitrogen isotopes (δ15Norg), we studied how lake trophic status and ecology respond to both climatic changes and anthropogenic impacts of the past 500 yrs at Lake Daihai, Inner Mongolia. The results show that the relative abundance of lipids, proteins, and carbohydrates in lake sediments kept relatively low before AD ∼1850, and increased gradually thereafter, especially after AD ∼1950, suggesting that the lake trophic status was low before AD ∼1850, but obviously increased during the past one more century. On the other hand, the relative abundance of allochthonous condensed aromatics and vascular plant-derived polyphenols compounds gradually decreased after AD ∼1850, which is most likely due to the intensified land-use changes in the catchment. Our results show that the SOM molecular composition is more sensitive to trace the land-use changes than the δ15Norg ratios, suggesting a potential use of this technique to trace even earlier human land uses (e.g., during the prehistorical times) in a catchment. The results of this study suggest that intensified land-use change, increased discharges of human sewage and industrial wastewater, cropland runoff, and concentrated effects caused by lake level drops may have combinedly increased nutrient concentration and accelerated lake eutrophication at Lake Daihai. Therefore, proper policy is necessary to slow down anthropogenic impacts and limit further eutrophication for lakes like Lake Daihai.


Assuntos
Sedimentos Geológicos , Lagos , Humanos , Lagos/química , Sedimentos Geológicos/análise , Eutrofização , Qualidade da Água , China , Nitrogênio/análise
6.
Atten Percept Psychophys ; 85(1): 209-221, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36369614

RESUMO

People can extract summary statistical information from groups of similar objects, an ability called ensemble perception. However, not every object in a group is weighted equally. For example, in ensemble emotion perception, faces far from fixation were weighted less than faces close to fixation. Yet the contribution of foveal input in ensemble emotion perception is still unclear. In two experiments, groups of faces with varying emotions were presented for 100 ms at three different eccentricities (0°, 3°, 8°). Observers reported the perceived average emotion of the group. In two conditions, stimuli consisted of a central face flanked by eight faces (flankers) (central-present condition) and eight faces without the central face (central-absent condition). In the central-present condition, the emotion of the central face was either congruent or incongruent with that of the flankers. In Experiment 1, flanker emotions were uniform (identical flankers); in Experiment 2 they were varied. In both experiments, performance in the central-present condition was superior at 3° compared to 0° and 8°. At 0°, performance was superior in the central-absent (i.e., no foveal input) compared to the central-present condition. Poor performance in the central-present condition was driven by the incongruent condition where the foveal face strongly biased responses. At 3° and 8°, performance was comparable between central-present and central-absent conditions. Our results showed how foveal input determined the perceived emotion of face ensembles, suggesting that ensemble perception fails when salient target information is available in central vision.


Assuntos
Emoções , Expressão Facial , Humanos , Emoções/fisiologia
7.
Front Aging Neurosci ; 14: 891644, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35813950

RESUMO

Background: Exercise plays an essential role in improving motor symptoms in Parkinson's disease (PD), but the underlying mechanism in the central nervous system remains unclear. Methods: Motor ability was observed after 12-week treadmill exercise on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. RNA-sequencing on four brain regions (cerebellum, cortex, substantia nigra (SN), and striatum) from control animals, MPTP-induced PD, and MPTP-induced PD model treated with exercise for 12 weeks were performed. Transcriptional networks on the four regions were further identified by an integrative network biology approach. Results: The 12-week treadmill exercise significantly improved the motor ability of an MPTP-induced mouse model of PD. RNA-seq analysis showed SN and striatum were remarkably different among individual region's response to exercise in the PD model. Especially, synaptic regulation pathways about axon guidance, synapse assembly, neurogenesis, synaptogenesis, transmitter transport-related pathway, and synaptic regulation genes, including Neurod2, Rtn4rl2, and Cd5, were upregulated in SN and striatum. Lastly, immunofluorescence staining revealed that exercise rescued the loss of TH+ synapses in the striatal region in PD mice, which validates the key role of synaptic regulation pathways in exercise-induced protective effects in vivo. Conclusion: SN and striatum are important brain regions in which critical transcriptional changes, such as in synaptic regulation pathways, occur after the exercise intervention on the PD model.

8.
Neurosci Biobehav Rev ; 132: 362-377, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34883165

RESUMO

This systematic review aims to 1) explore the association between tic disorders (TD) and allergic diseases (AD), 2) judge whether patients with a diagnosis of TD are prone to suffer from a specific AD, by compiling the literature and analyzing the evidence. A literature search was conducted in PubMed and Embase database on February 24, 2021. The inclusion criteria for the literature were all comparative studies that reported TD patients were diagnosed with allergic illness as well. We identified that TD is positively associated with asthma, allergic rhinitis and allergic conjunctivitis, respectively. Especially, provisional tic disorder (PTD) patients might be more likely to suffer from these three AD, although it is still difficult to accurately predict which specific AD is prone to be accompanied by a specific TD. Shared genetic and etiological factors are suggested responsible for the AD-TD association. Large prospective cohort studies in future might shed light on a deep understanding of the relationship between immune disorders and tics.


Assuntos
Asma , Rinite Alérgica , Transtornos de Tique , Tiques , Humanos , Estudos Prospectivos , Rinite Alérgica/complicações
9.
Int Heart J ; 60(5): 1077-1082, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31447466

RESUMO

Patients with ST-segment elevation myocardial infarction (STEMI) who are treated by primary percutaneous coronary intervention (PPCI) have an increased risk of developing contrast-induced nephropathy (CIN) when compared with patients undergoing elective percutaneous coronary intervention (PCI). However, CIN prevention measures are less frequently applied in PPCI than in elective PCI. At present, no preventive strategy has been recommended by the current guidelines for patients with STEMI undergoing PPCI.Published research was scanned by formal searches of electronic databases (PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials) from 1966 to July 2018. Internet-based sources of information on the results of clinical trials in cardiology were also searched.A total of three randomized trials involving 924 patients were included in the present meta-analysis, of whom 462 received hydration with isotonic saline (hydration group) and 462 received no hydration (control group). Periprocedural hydration with isotonic saline was associated with a significant decrease in the rate of CIN (16.9% in the hydration group versus 26.4% in the control group; summary risk ratio: 0.64, 95% confidence interval: 0.50-0.82, P = 0.0005). There was no difference in the rate of postprocedural hemodialysis or death between the groups.Intravenous saline hydration during PPCI reduced the risk of CIN without significantly altering the rate of requirement for renal replacement therapy or mortality.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/terapia , Meios de Contraste/efeitos adversos , Hidratação/métodos , Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Injúria Renal Aguda/prevenção & controle , Idoso , Angiografia Coronária/efeitos adversos , Angiografia Coronária/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Análise de Sobrevida , Resultado do Tratamento
11.
EBioMedicine ; 39: 409-421, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30522932

RESUMO

BACKGROUND: It is widely accepted that cognitive and memory deficits in Alzheimer's disease (AD) primarily result from synaptic failure. However, the mechanisms that underlie synaptic and cognitive dysfunction remain unclear. METHODS: We utilized molecular biology techniques, electrophysiological recordings, fluorescence in situ hybridization (FISH), immuno- and Golgi-staining, chromatin immunoprecipitation (CHIP); lentivirus (LV)-based microRNA overexpression and 'sponging', and behavioral tests to assess upregulated miR-30b causing synaptic and cognitive declines in APP transgenic (TG) mice. FINDINGS: We provide evidence that expression of miR-30b, which targets molecules important for maintaining synaptic integrity, including ephrin type-B receptor 2 (ephB2), sirtuin1 (sirt1), and glutamate ionotropic receptor AMPA type subunit 2 (GluA2), is robustly upregulated in the brains of both AD patients and APP transgenic (TG) mice, an animal model of AD, while expression of its targets is significantly downregulated. Overexpression of miR-30b in the hippocampus of normal wild-type (WT) mice impairs synaptic and cognitive functions, mimicking those seen in TG mice. Conversely, knockdown of endogenous miR-30b in TG mice prevents synaptic and cognitive decline. We further observed that expression of miR-30b is upregulated by proinflammatory cytokines and Aß42 through NF-κB signaling. INTERPRETATION: Our results provide a previously undefined mechanism by which unregulated miR-30b causes synaptic and cognitive dysfunction in AD, suggesting that reversal of dysregulated miR-30b in the brain may prevent or slow cognitive declines in AD. FUND: This work was supported by National Institutes of Health grants R01NS076815, R01MH113535, R01AG058621, P30GM103340 Pilot Project, and by the LSUHSC School of Medicine Research Enhancement Program grant (to C.C.).


Assuntos
Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Disfunção Cognitiva/genética , MicroRNAs/genética , Doença de Alzheimer/psicologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Transgênicos , Transdução de Sinais , Potenciais Sinápticos
12.
Se Pu ; 36(3): 309-316, 2018 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-30136511

RESUMO

A rapid and sensitive method was established for the analysis of peptide antibiotics (bacitracin, polymyxin B and colistin) in animal food by capillary electrochromatography (CEC) coupled with laser induced fluorescence (LIF) using 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) as fluorogenic reagent. Peptide antibiotics were derivatized by NBD-F in 50 mmol/L borate buffer (pH 7.5) for 45 min at 60℃. The fluorescence derivatives of peptide antibiotics were separated on a packed phenyl capillary column with a mobile phase consisting of acetonitrile-potassium phosphate (pH 5.0, 10 mmol/L) (55:45, v/v) at the flow rate of 0.02 mL/min. A supplementary pressure of 3.8 MPa and a separation voltage of -10 kV were applied. The limits of detection (LODs, S/N=3) were 5.0-10.0 ng/mL, which fulfilled the requirement of maximum residue limits for examined peptide antibiotics. The method was applied to detect peptide antibiotics in milk and feed stuffs. The spiked recoveries of the three peptide antibiotics were 72.9%-112.4%. The method shows some advantages on the simpler pretreatment and higher sensitivity, which can be of great benefit to the residual analysis of the veterinary drugs.


Assuntos
Ração Animal/análise , Antibacterianos/análise , Eletrocromatografia Capilar , Fluorescência , Peptídeos/análise , Indicadores e Reagentes
13.
Exp Neurol ; 308: 59-71, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29959908

RESUMO

Many studies have demonstrated that mesencephalic astrocyte-derived neurotrophic factor (MANF) has been shown protective effects on neurotoxin based models of Parkinson's disease (PD). It still remains unclear whether MANF can rescue dopaminergic (DA) neurons in an α-synuclein model. Glial cell line-derived neurotrophic factor (GDNF) and its related neurturin (NRTN) can protect DA neurons in the neurotoxin but not α-synuclein animal models of PD, it failed in the clinical trials. Since α-synuclein model can better mimic the progression of human PD, in our study we overexpressed MANF specifically in DA neurons by using an α-synuclein Caenorhabditis elegans (C. elegans) model. Our results showed MANF alleviated progressive neuronal degeneration and prevented locomotion defects. Indeed, MANF can protect cilia of DA neurons at an early stage, suggested that MANF participated in the whole process of neuronal degeneration. Furthermore, we found MANF facilitated the removal of misfolded α-synuclein proteins and rescued the function of damaged DA neurons. By using RNAi approach, we inhibited ER stress and autophagy related genes and effects of MANF were decreased, which demonstrated ER stress and autophagy pathways were involved in the MANF-mediated neuroprotection. Our study suggests MANF exhibits potential as a neuroprotective agent for PD therapy.


Assuntos
Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Estresse do Retículo Endoplasmático/fisiologia , Fatores de Crescimento Neural/metabolismo , Transtornos Parkinsonianos/fisiopatologia , alfa-Sinucleína/metabolismo , Animais , Animais Geneticamente Modificados , Autofagia/fisiologia , Caenorhabditis elegans , Modelos Animais de Doenças , Humanos , Locomoção/fisiologia , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Degeneração Neural/fisiopatologia , Neuroproteção/fisiologia , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/patologia
14.
Sci Rep ; 5: 16257, 2015 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-26541090

RESUMO

The endocannabinoid 2-arachidonoylglycerol (2-AG) functions as a retrograde signaling molecule mediating synaptic transmission and plasticity at both inhibitory and excitatory synapses. However, little is known about whether 2-AG signaling is involved in homeostatic regulation of miniature synaptic events at excitatory synapses in response to activity deprivation. Here, we report that chronic blockade of firing by tetrodotoxin (TTX) for two days resulted in increases both in the frequency and amplitude of spontaneous miniature excitatory postsynaptic currents (mEPSCs) in cultured mouse hippocampal neurons. However, treatment with 2-AG alone or JZL184, a potent and selective inhibitor for monoacylglycerol lipase (MAGL) that hydrolyzes 2-AG, induced a CB1 receptor-dependent reduction of the frequency of mEPSCs, but not the amplitude. The TTX-increased frequency was blunted by 2-AG or JZL184 and this effect was eliminated by pharmacological or genetic inhibition of CB1 receptors. In addition, TTX still increased frequency and amplitude of mEPSCs in the presence of CB1 receptor inhibition. Our results suggest that while endocannabinoids are not required for induction of synaptic scaling at excitatory glutamate synapses after chronic activity deprivation, 2-AG signaling may play a role in fine-tuning of synaptic strengths via presynaptically-expressed CB1 receptors.


Assuntos
Endocanabinoides/metabolismo , Receptor CB1 de Canabinoide/fisiologia , Transdução de Sinais , Sinapses/metabolismo , Animais , Ácidos Araquidônicos/farmacologia , Células Cultivadas , Endocanabinoides/farmacologia , Hipocampo/citologia , Hipocampo/metabolismo , Camundongos , Alcamidas Poli-Insaturadas/farmacologia
16.
Electrophoresis ; 36(16): 1953-61, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25873262

RESUMO

A coupling method of field-amplified sample injection (FASI) CE with amperometric detection is developed for ultratrace analysis of ephedrine alkaloids stereoisomers. FASI was introduced by injecting electrokinetically the sample solution for 10 s into the capillary filled with highly conductive background electrolyte (BGE). The diastereomeric selectivity and the detection sensitivity were improved by using borate buffer of high ionic strength as BGE. Parameters affecting FASI and CE separation were investigated to achieve the optimal conditions. Four analytes were separated within 15 min using 200 mmol/L borate buffer (pH 9.5) and separation voltage of +18 kV, with detection potential at +1.0 V (vs. Ag/AgCl) and carbon disc electrode as working electrode. Excellent linearity was observed between peak current and concentration of analytes in the range of 0.1-100 ng/mL. The LODs (S/N = 3) for (-)-ephedrine, (+)-pseudoephedrine, (-)-N-methylephedrine and (+)-N-methylpseudoephedrine were 39.3, 54.9, 30.8, and 44.1 pg/mL, respectively. The proposed method was successfully applied to the determination of alkaloids in Ephedra sinica, with results agreed well with HPLC method. Mean recoveries of 102.1-109.7% and RSDs less than 6% were found. And the merits of high sensitivity and selectivity, as well as a simple and stable operation, have been demonstrated.


Assuntos
Alcaloides/análise , Alcaloides/química , Eletroforese Capilar/métodos , Efedrina/análise , Efedrina/química , Eletrodos , Hidrodinâmica , Concentração de Íons de Hidrogênio , Reprodutibilidade dos Testes , Estereoisomerismo
17.
J Cereb Blood Flow Metab ; 35(3): 443-53, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25492114

RESUMO

Emerging evidence suggests that the risk of developing chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease, is significantly increased in military personnel and contact sports players who have been exposed to repetitive trauma brain injury (TBI). Unfortunately there are no effective medications currently available for prevention and treatment of CTE. Here we demonstrate that inhibition of monoacylglycerol lipase (MAGL), the key enzyme that metabolizes the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain, significantly reduced CTE-like neuropathologic changes in a mouse model of repetitive mild closed head injury (rmCHI). Inhibition of 2-AG metabolism promoted neurologic recovery following rmCHI and reduced proinflammatory cytokines, astroglial reactivity, expression of amyloid precursor protein and the enzymes that make Aß, as well as formation of Aß. Importantly, neurodegeneration, TDP-43 protein aggregation, and tau phosphorylation, which are the neuropathologic hallmarks of CTE, were significantly suppressed by MAGL inactivation. Furthermore, alterations in expression of glutamate receptor subunits and impairments in basal synaptic transmission, long-term synaptic plasticity, and spatial learning and memory were recovered by inhibition of 2-AG metabolism in animals exposed to rmCHI. Our results suggest that MAGL inhibition, which boosts 2-AG and reduces 2-AG metabolites prostaglandins in the brain, may lead to a new therapy for CTE.


Assuntos
Ácidos Araquidônicos/metabolismo , Lesão Encefálica Crônica/metabolismo , Endocanabinoides/metabolismo , Glicerídeos/metabolismo , Monoacilglicerol Lipases/metabolismo , Animais , Western Blotting , Modelos Animais de Doenças , Traumatismos Cranianos Fechados/complicações , Traumatismos Cranianos Fechados/metabolismo , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Cultura de Órgãos , Técnicas de Patch-Clamp , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
Org Biomol Chem ; 12(13): 2099-107, 2014 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-24553740

RESUMO

An efficient procedure for the syntheses of pyrazolo[1,5-a]pyrimidines through reactions of 1,2-allenic ketones with aminopyrazoles under extremely mild conditions without using any catalyst or promoter has been developed. The reactions showed excellent regio-selectivity with all the allenic ketone substrates except for those bearing an alkyl group at the internal position of the allene moiety. The reason behind this regio-selectivity dissimilarity has been explored with the aid of the B3LYP/6-31G* level of density functional theory. Moreover, this novel procedure has been successfully applied in the preparation of nucleoside-pyrazolo[1,5-a]pyrimidine chimeras with potent antiviral activities.


Assuntos
Cetonas/química , Pirazóis/química , Pirimidinas/síntese química , Estrutura Molecular , Pirazóis/síntese química , Pirimidinas/química , Teoria Quântica , Estereoisomerismo
19.
Cell ; 155(5): 1154-1165, 2013 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-24267894

RESUMO

Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here, we show that synaptic and cognitive impairments following repeated exposure to Δ(9)-tetrahydrocannabinol (Δ(9)-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids in the brain. COX-2 induction by Δ(9)-THC is mediated via CB1 receptor-coupled G protein ßγ subunits. Pharmacological or genetic inhibition of COX-2 blocks downregulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ(9)-THC exposures. Ablation of COX-2 also eliminates Δ(9)-THC-impaired hippocampal long-term synaptic plasticity, working, and fear memories. Importantly, the beneficial effects of decreasing ß-amyloid plaques and neurodegeneration by Δ(9)-THC in Alzheimer's disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Dronabinol/farmacologia , Memória/efeitos dos fármacos , Transdução de Sinais , Sinapses/efeitos dos fármacos , Animais , Cannabis/química , Ciclo-Oxigenase 2/genética , Hipocampo/citologia , Hipocampo/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/metabolismo , Receptor CB1 de Canabinoide/metabolismo
20.
Pharmacology ; 89(3-4): 156-62, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22414722

RESUMO

BACKGROUND: Minocycline has demonstrated neuroprotective effects in experimental neurodegenerative diseases. The aim of this study was to investigate if there is any direct interaction between minocycline and the AMPA-type receptor channels, and to elucidate the underlying molecular pharmacological mechanisms. METHODS: The patch-clamp technique was used combined with an ultrafast solution exchange system to investigate the interaction of minocycline with recombinant AMPA-type glutamate receptor channels (homomeric GluR2flipGQ or nondesensitizing GluR2L504Y). RESULTS: Dose-dependent decreases in the relative peak current amplitude (rAmp) and the relative steady-state current (rC(des)) were found in coapplication experiments with GluR2L504Y receptors, but not in preincubation experiments. Furthermore, coapplication of 1 or 3 mmol/l minocycline showed a decrease in the fast time constant of current decay, and reopening currents were observed. But in the test with GluR2flipGQ receptors, rAmp, relative area under the curve and rC(des) increased with increasing concentrations of minocycline, and the steady-state time constant also increased when 3 µmol/l glutamate were used as agonist. CONCLUSION: Minocycline modulates AMPA-type receptor channels in a combination of a weaker open-channel block effect and a stronger potentiation effect, and the latter effect arises mainly from attenuating the extent of receptor desensitization.


Assuntos
Minociclina/farmacologia , Fármacos Neuroprotetores/farmacologia , Receptores de AMPA/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Células HEK293 , Humanos , Técnicas de Patch-Clamp , Receptores de AMPA/fisiologia
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