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1.
Microbiol Spectr ; 10(1): e0105321, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35138162

RESUMO

It is well known that humans physiologically or pathologically respond to high altitude, with these responses accompanied by alterations in the gut microbiome. To investigate whether gut microbiota modulation can alleviate high-altitude-related diseases, we administered probiotics, prebiotics, and synbiotics in rat model with altitude-related cardiac impairment after hypobaric hypoxia challenge and observed that all three treatments alleviated cardiac hypertrophy as measured by heart weight-to-body weight ratio and gene expression levels of biomarkers in heart tissue. The disruption of gut microbiota induced by hypobaric hypoxia was also ameliorated, especially for microbes of Ruminococcaceae and Lachnospiraceae families. Metabolome revealed that hypobaric hypoxia significantly altered the plasma short-chain fatty acids (SCFAs), bile acids (BAs), amino acids, neurotransmitters, and free fatty acids, but not the overall fecal SCFAs and BAs. The treatments were able to restore homeostasis of plasma amino acids and neurotransmitters to a certain degree, but not for the other measured metabolites. This study paves the way to further investigate the underlying mechanisms of gut microbiome in high-altitude related diseases and opens opportunity to target gut microbiome for therapeutic purpose. IMPORTANCE Evidence suggests that gut microbiome changes upon hypobaric hypoxia exposure; however, it remains elusive whether this microbiome change is a merely derivational reflection of host physiological alteration, or it synergizes to exacerbate high-altitude diseases. We intervened gut microbiome in the rat model of prolonged hypobaric hypoxia challenge and found that the intervention could alleviate the symptoms of pathological cardiac hypertrophy, gut microbial dysbiosis, and metabolic disruptions of certain metabolites in gut and plasma induced by hypobaric hypoxia. Our study suggests that gut microbiome may be a causative factor for high-altitude-related pathogenesis and a target for therapeutic intervention.


Assuntos
Cardiomegalia/metabolismo , Cardiomegalia/microbiologia , Microbioma Gastrointestinal , Altitude , Aminoácidos/sangue , Animais , Ácidos e Sais Biliares/sangue , Biomarcadores/sangue , Cardiomegalia/terapia , Ácidos Graxos Voláteis/sangue , Humanos , Masculino , Metaboloma , Neurotransmissores/sangue , Ratos , Ratos Wistar
2.
Reprod Biol Endocrinol ; 20(1): 16, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35042515

RESUMO

Sleep is vital to human bodily function. Growing evidence indicates that sleep deprivation, disruption, dysrhythmia, and disorders are associated with impaired reproductive function and poor clinical outcomes in women. These associations are largely mediated by molecular-genetic and hormonal pathways, which are crucial for the complex and time sensitive processes of hormone synthesis/secretion, folliculogenesis, ovulation, fertilization, implantation, and menstruation. Pathologic sleep patterns are closely linked to menstrual irregularity, polycystic ovarian syndrome, premature ovarian insufficiency, sub/infertility, and early pregnancy loss. Measures of success with assisted reproductive technology are also lower among women who engage in shift work, or experience sleep disruption or short sleep duration. Extremes of sleep duration, poor sleep quality, sleep disordered breathing, and shift work are also associated with several harmful conditions in pregnancy, including gestational diabetes and hypertensive disorders. While accumulating evidence implicates pathologic sleep patterns in impaired reproductive function and poor reproductive outcomes, additional research is needed to determine causality and propose therapeutic interventions.


Assuntos
Neurotransmissores/sangue , Reprodução/fisiologia , Sono/fisiologia , Feminino , Humanos , Infertilidade Feminina/sangue , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/etiologia , Gravidez , Prognóstico , Fatores de Risco , Qualidade do Sono
3.
Medicine (Baltimore) ; 100(49): e27867, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34889236

RESUMO

ABSTRACT: This study analyzed the Val158Met polymorphisms of the catechol-O-methyltransferase (COMT) gene and serum concentrations of catecholaminergic neurotransmitters in attention deficit hyperactivity disorder (ADHD) children and adolescents.All the subjects (180 paired ADHD and non-ADHD children and adolescents) were genotyped for the Val158Met polymorphisms of the COMT gene, and determined by the difference of dopamine and noradrenalin from a 1:1 paired case-control study.The frequencies of methionine (A)/A, valine (G)/A, and G/G were 51.67%, 41.11%, and 7.22% in the case group, and 62.22%, 31.11%, and 6.67% in the control group. There was a significant difference in the distribution of all genotypes of the COMT gene between the 2 groups (odds ratio = 1.85, 95% confidence interval: 1.62-2.08; χ2 = 7.80, P < .05). The serum concentrations of dopamine and noradrenalin were 1.42 ±â€Š0.34 ng/mL and 177.70 ±â€Š37.92 pg/mL in the case group, and 1.94 ±â€Š0.42 ng/mL and 206.20 ±â€Š42.45 pg/mL in the control group. There were the significant differences in the levels of dopamine and noradrenalin between the 2 groups (dopamine: t = 4.30, P < .01; noradrenalin: t = 2.24, P < .05).Our study suggested that the Val158Met polymorphisms of the COMT gene and serum concentrations of catecholaminergic neurotransmitters were associated with ADHD children and adolescents.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Catecol O-Metiltransferase/genética , Dopamina/sangue , Neurotransmissores/sangue , Adolescente , Estudos de Casos e Controles , Criança , China , Feminino , Genótipo , Humanos , Masculino
4.
Mol Med ; 27(1): 154, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34875999

RESUMO

BACKGROUND: The incidence of diabetes mellitus (DM) and depression is increasing year by year around the world, bringing a serious burden to patients and their families. Jiao-tai-wan (JTW), a well-known traditional Chinese medicine (TCM), has been approved to have hypoglycemic and antidepressant effects, respectively, but whether JTW has such dual effects and its potential mechanisms is still unknown. This study is to evaluate the dual therapeutic effects of JTW on chronic restraint stress (CRS)-induced DM combined with depression mice, and to explore the underlying mechanisms through network pharmacology. METHODS: CRS was used on db/db mice for 21 days to induce depression-like behaviors, so as to obtain the DM combined with depression mouse model. Mice were treated with 0.9% saline (0.1 ml/10 g), JTW (3.2 mg/kg) and Fluoxetine (2.0 mg/kg), respectively. The effect of JTW was accessed by measuring fasting blood glucose (FBG) levels, conducting behavioral tests and observing histopathological change. The ELISA assay was used to evaluate the levels of inflammatory cytokines and the UHPLC-MS/MS method was used to determine the depression-related neurotransmitters levels in serum. The mechanism exploration of JTW against DM and depression were performed via a network pharmacological method. RESULTS: The results of blood glucose measurement showed that JTW has a therapeutic effect on db/db mice. Behavioral tests and the levels of depression-related neurotransmitters proved that JTW can effectively ameliorate depression-like symptoms in mice induced by CRS. In addition, JTW can also improve the inflammatory state and reduce the number of apoptotic cells in the hippocampus. According to network pharmacology, 28 active compounds and 484 corresponding targets of JTW, 1407 DM targets and 1842 depression targets were collected by screening the databases, and a total of 117 targets were obtained after taking the intersection. JTW plays a role in reducing blood glucose level and antidepressant mainly through active compounds such as quercetin, styrene, cinnamic acid, ethyl cinnamate, (R)-Canadine, palmatine and berberine, etc., the key targets of its therapeutic effect include INS, AKT1, IL-6, VEGF-A, TNF and so on, mainly involved in HIF-1 signal pathway, pathways in cancer, Hepatitis B, TNF signal pathway, PI3K-Akt signal pathway and MAPK signaling pathway, etc. CONCLUSION: Our experimental study showed that JTW has hypoglycemic and antidepressant effects. The possible mechanism was explored by network pharmacology, reflecting the characteristics of multi-component, multi-target and multi-pathway, which provides a theoretical basis for the experimental research and clinical application of JTW in the future.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Hipoglicemiantes/uso terapêutico , Animais , Antidepressivos/farmacologia , Apoptose/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Proteína C-Reativa/análise , Citocinas/sangue , Depressão/genética , Depressão/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Hipocampo/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Farmacologia em Rede , Neurotransmissores/sangue , Mapas de Interação de Proteínas
5.
Life Sci ; 284: 119904, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34453945

RESUMO

AIM: Alcohol abuse is a significant causative factor of death worldwide. The Notch1 signaling pathway is involved in alcohol tolerance, withdrawal and dependence. Agomelatine is a known antidepressant acting as a melatonin receptor (MT1/2) agonist and a 5-hydroxytryptamine receptor-2C antagonist. However, its effects on alcohol cravings and alcohol withdrawal symptoms have not been investigated. In this study, we assessed the possibility of using agomelatine for the treatment of these symptoms in a rat model of alcoholism and the possible role of Notch1 signaling. MAIN METHODS: We induced alcoholism in rats using a free-choice drinking model for 60 days. From day 61, free-choice was continued until day 82 for the craving model, whereas only water was offered in the withdrawal model. Meanwhile, the treated groups for both models received agomelatine (50 mg/kg/day) orally from day 61 to 82, followed by behavioral, histopathological and biochemical assessment. KEY FINDINGS: Agomelatine treatment caused significant decrease in alcohol consumption with a positive effect on anxiety-like behavior in the open field, memory in the Morris water maze and immobility in the forced swim test. Moreover, agomelatine induced the expression of Notch1 pathway markers, including Notch1, NICD, CREB, CCNE-2, Hes-1, both total and phosphorylated ERK1/2, MMP9, Per2and RGS-2 in the hippocampal formation. By contrast, NMDAR expression was reduced. Furthermore, agomelatine normalized the serum levels of BDNF, cortisol, dopamine and glutamate which were disrupted by alcohol consumption. SIGNIFICANCE: Based on these findings, agomelatine reversed alcohol cravings and withdrawal symptoms associated with alcohol dependence by modulating the Notch1 signaling pathway.


Assuntos
Acetamidas/uso terapêutico , Bebidas Alcoólicas/efeitos adversos , Fissura , Receptor Notch1/metabolismo , Transdução de Sinais , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Síndrome de Abstinência a Substâncias/metabolismo , Acetamidas/farmacologia , Animais , Ansiedade/patologia , Comportamento Animal/efeitos dos fármacos , Biomarcadores/metabolismo , Ritmo Circadiano/efeitos dos fármacos , Hipocampo/metabolismo , Hidrocortisona/sangue , Masculino , Teste do Labirinto Aquático de Morris , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Neurotransmissores/sangue , Teste de Campo Aberto , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
6.
Sci Rep ; 11(1): 15854, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34349208

RESUMO

Various efforts have been made to detect minimum amounts of any toxic materials in water or the neurotoxic effect of venom (Odontobuthus Doriae Scorpion) in the human's blood serum nerve by high-sensitivity, accurate, and low-cost sensors in order to enhance life style. Therefore, the present study was done to investigate reliability of two-dimensional plasmonic structure and circular dichroism (CD) in toxic samples in order to measure and determine venom concentrations and its neurotoxic effect on humans҆ blood serum Neurotransmitter analytes. Our results confirmed dependency of CD signal to neurotoxic effect of venom concentrations and good sensitivity of this sensor with the help of achiral plasmonic structure.


Assuntos
Técnicas Biossensoriais/métodos , Neurônios/patologia , Neurotransmissores/sangue , Venenos de Escorpião/efeitos adversos , Escorpiões/química , Animais , Humanos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ressonância de Plasmônio de Superfície
7.
Artigo em Inglês | MEDLINE | ID: mdl-34329893

RESUMO

This study aimed to establish a sensitive, reproducible, and rapid liquid chromatography method with tandem mass spectrometry detection to perform simultaneous quantitative analysis of 16 neurotransmitters and their metabolites in rat plasma, including levodopa, dopamine, norepinephrine, epinephrine, L-tryptophan, kynurenic acid, serotonin, melatonin, choline, acetylcholine, histamine, phenylethylamine, as well as excitatory (L-glutamic acid and L-aspartic acid) and inhibitory (γ-aminobutyric acid and L-glycine) neurotransmitters. These analytes were measured by ultra-high performance chromatography coupled with triple quadrupole mass spectrometry using a hydrophilic interaction chromatographic column (ethylene-bridged hybrid amide column). The internal standards of stable isotope labeling were used to improve the reliability of the results. Our method provided high linearity for all neurotransmitters (for all coefficients measured > 0.99), with inter- and intra-day accuracy from -14.82% to 17.49% and precision was between 0.89% and 17.70%. The method was subsequently verified in an animal study, where the intervention of five different Uncarias, the traditional Chinese medicine with hypotensive effects, was applied to the spontaneously hypertensive rats (SHRs). SHRs showed dysregulated plasma kynurenic acid, acetylcholine, and norepinephrine levels, and these neuroactive analytes were significantly restored by Uncaria treatment compared with the model group (SHR group). Compared with captopril, included as a positive control for its hypotensive effect, Uncaria had more effects on perturbing the levels of plasma neurotransmitters, which might indicate Uncaria's potential in treating symptoms related to the nervous system. These results suggested that the changes in the neurotransmitters and their metabolites in plasma may be related to the pathogenesis of hypertension. It also provided valuable information about the action mechanisms of Uncaria on its hypotensive effects.


Assuntos
Medicamentos de Ervas Chinesas , Neurotransmissores/sangue , Uncaria , Animais , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Limite de Detecção , Modelos Lineares , Masculino , Espectrometria de Massas , Metaboloma/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Reprodutibilidade dos Testes
8.
Anal Bioanal Chem ; 413(27): 6803-6812, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33774711

RESUMO

This work highlights the protocol employed for the simultaneous electroanalysis of tryptamine, serotonin and dopamine using a conducting poly-murexide-based electrode. To date, this is the first-of-its-kind report of simultaneous electrochemical determination of these three targets. Features of the developed electrode were identified by employing FE-SEM analysis. Under optimized conditions, the analytes underwent an irreversible electro-oxidation at the modified electrode surface, with a linear range of 0.5-40 µΜ, 0.4-40.4 µΜ and 0.5-40 µΜ for dopamine, serotonin and tryptamine, respectively. The electrolytic medium employed for the sensing was a phosphate-buffered solution with pH 7. The specificity of the developed electrode was also satisfactory in the presence of other biomolecules including L-phenylalanine, L-serine, glucose and ascorbic acid. Thus, the developed murexide-derived conducting-polymer-based electrode was used for the simultaneous sensing of the neurochemicals dopamine, serotonin and tryptamine. Electroanalysis was also demonstrated for these targets in human serum.


Assuntos
Técnicas Eletroquímicas/métodos , Murexida/química , Neurotransmissores/análise , Dopamina/análise , Dopamina/sangue , Técnicas Eletroquímicas/instrumentação , Eletrodos , Grafite/química , Humanos , Concentração de Íons de Hidrogênio , Limite de Detecção , Microscopia Eletrônica de Varredura , Neurotransmissores/sangue , Oxirredução , Reprodutibilidade dos Testes , Serotonina/análise , Serotonina/sangue , Triptaminas/análise , Triptaminas/sangue
9.
Mol Genet Metab ; 133(1): 56-62, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33744095

RESUMO

OBJECTIVE: Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare inherited autosomal recessive disorder of biogenic amine metabolism. Diagnosis requires analysis of neurotransmitter metabolites in cerebrospinal fluid, AADC enzyme activity analysis, or molecular analysis of the DDC gene. 3-O-methyldopa (3-OMD) is a key screening biomarker for AADC deficiency. METHODS: We describe a rapid method for 3-OMD determination in dried blood spots (DBS) using flow-injection analysis tandem mass spectrometry with NeoBase™ 2 reagents and 13C6-tyrosine as an internal standard, which are routinely used in high-throughput newborn screening. We assessed variability using quality control samples over a range of 3-OMD concentrations. RESULTS: Within-day and between-day precision determined with quality control samples demonstrated coefficients of variation <15%. 3-OMD concentrations in 1000 healthy newborns revealed a mean of 1.33 µmol/L (SD ± 0.56, range 0.61-3.05 µmol/L), 100 non-AADC control subjects (age 7 days - 1 year) showed a mean of 1.19 µmol/L (SD ± 0.35-2.00 µmol/L), and 81 patients receiving oral L-Dopa had a mean 3-OMD concentration of 14.90 µmol/L (SD ± 14.18, range 0.4-80.3 µmol/L). A patient with confirmed AADC was retrospectively analyzed and correctly identified (3-OMD 10.51 µmol/L). In April 2020, we started a pilot project for identifying AADC deficiency in DBSs routinely submitted to the expanded newborn screening program. 3-OMD concentrations were measured in 21,867 samples; no patients with AADC deficiency were identified. One newborn had a high 3-OMD concentration due to maternal L-Dopa treatment. DISCUSSION: We demonstrated a rapid new method to identify AADC deficiency using reagents and equipment already widely used in newborn screening programs. Although our study is limited, introduction of our method in expanded neonatal screening is feasible and could facilitate deployment of screening, allowing for early diagnosis that is important for effective treatment.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/sangue , Descarboxilases de Aminoácido-L-Aromático/sangue , Descarboxilases de Aminoácido-L-Aromático/deficiência , Triagem Neonatal , Tirosina/análogos & derivados , Erros Inatos do Metabolismo dos Aminoácidos/epidemiologia , Erros Inatos do Metabolismo dos Aminoácidos/genética , Erros Inatos do Metabolismo dos Aminoácidos/patologia , Descarboxilases de Aminoácido-L-Aromático/genética , Dopamina/sangue , Feminino , Humanos , Recém-Nascido , Itália/epidemiologia , Levodopa/sangue , Masculino , Neurotransmissores/sangue , Espectrometria de Massas em Tandem , Tirosina/sangue
10.
Biomed Chromatogr ; 35(6): e5084, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33559223

RESUMO

Emerging evidence suggests that amino acid (AA) neurotransmitters play important roles in the pathophysiological processes of cerebral ischemia. In this work, an HPLC with fluorescence detection (HPLC-FLR) method was developed for the simultaneous determination of 18 AAs in the cortex and plasma after cerebral ischemia in mice. The ischemia model was prepared by bilateral common carotid artery occlusion, and then the cortex and plasma of the sham, ischemia, and naringenin groups were collected. Based on the protein precipitation method, a simple and effective sample preparation method was developed. The treated sample contained minimal proteins and lipids. The analysis of the sample was performed by the proposed HPLC-FLR method in combination with o-phthalaldehyde. The results showed a statistically significant increase in excitatory AAs (aspartic acid and glutamic acid), inhibitory AAs (glycine and 4-aminobutyric acid), phenylalanine, citrulline, isoleucine, and leucine levels, and a decrease of glutathione and phenylalanine levels when compared with the sham group in the cortex. Besides, the administration of naringenin had significant effects on excitatory AAs, inhibitory AA (glycine), glutamine, tyrosine, phenylalanine, and leucine levels when compared with the sham group in the cortex. These findings could be utilized in studying and clarifying the mechanisms of ischemia.


Assuntos
Aminoácidos/sangue , Isquemia Encefálica/metabolismo , Córtex Cerebral/química , Animais , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurotransmissores/sangue
11.
ACS Appl Mater Interfaces ; 13(9): 10987-10995, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33624494

RESUMO

Real-time monitoring of neurotransmitter levels is of tremendous technological demand, which requires more sensitive and selective sensors over a dynamic concentration range. As a use case, we report yttrium vanadate within three-dimensional graphene aerogel (YVO/GA) as a novel electrocatalyst for detecting dopamine (DA). This synergy effect endows YVO/GA nanocomposite with good electrochemical behaviors for DA detection compared to other electrodes. Benefiting from tailorable properties, it provides a large specific surface area, rapid electron transfer, more active sites, good catalytic activity, synergic effect, and high conductivity. The essential analytical parameters were estimated from the calibration plot, such as a limit of detection (1.5 nM) and sensitivity (7.1 µA µM-1 cm-2) with the YVO/GA sensor probe electrochemical approach. The calibration curve was fitted with the correlation coefficient of 0.994 in the DA concentration range from 0.009 to 83 µM, which is denoted as the linear working range. We further demonstrate the proposed YVO/GA sensor's applicability to detect DA in human serum sample with an acceptable recovery range. Our results imply that the developed sensor could be applied to the early analysis of dementia, psychiatric, and neurodegenerative disorders.


Assuntos
Dopamina/sangue , Grafite/química , Neurotransmissores/sangue , Vanadatos/química , Técnicas Eletroquímicas/métodos , Géis/química , Humanos , Limite de Detecção , Monitorização Fisiológica , Nanocompostos/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ítrio/química
12.
Eur Rev Med Pharmacol Sci ; 25(2): 880-889, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33577042

RESUMO

OBJECTIVE: To explore the correlation between neuropsychiatric status and blood neurotransmitter in lead workers, and to provide theoretical basis for the prevention and treatment of lead workers. SUBJECTS AND METHODS: The study applied cross-sectional survey, 74 occupational lead exposed workers in a battery factory in a city of Hebei province were selected as the lead exposed group, and 62 workers (non-lead workers) were selected as the control group. The occupational health symptoms questionnaire and health examination and POMS (Profile of Mood State, POMS) emotional test questionnaire were applied to investigate the nearly emotional status of the studied objects, ICP-MS was used to determine the blood lead level of all subjects, HPLC (High performance liquid chromatography, HPLC) was applied to determine the concentration of neurotransmitter in peripheral blood of all studied subjects, and all results were applied the Pearson's correlation analysis. RESULTS: The blood lead concentration of the lead workers group (163.23±40.77 ug/L) was significantly higher than that in the control group (43.62±14.50 ug/L), and the difference was statistically significant. From the analysis of neuropsychiatric status, the neurological symptoms in the lead workers group were higher than that in the control group, among which the symptoms of sleep disturbance, dizziness, fatigue, numbness of limbs and dampness and coldness of limbs were more obvious. Among the symptoms of digestive system, the incidence of abdominal pain, abdominal distension, constipation and nausea and vomiting were higher. According to the POMS emotion questionnaire, the scores of 5 negative emotions and 1 positive emotion in the lead exposure group were higher than that in the control group, and the difference was statistically significant. Related to the control group, the concentration of neurotransmitters such as DA, 5-HT, GABA, Gly, Trp and Glu were statistically decreased, p<0.001. There was a negative correlation between neurotransmitters in peripheral blood and blood lead levels in lead workers, among which 5-HT had the greatest correlation with lead levels (r=-0.569, p<0.001). 5-HT and Trp were significantly correlated with tension-anxiety (T), depression-depression (D), anger-hostility (A), Vigor-hyperactivity (V), fatigue-inertia (F), and confusion-confusion (C). 5-HT, Trp and GABA were significantly correlated with the survey symptoms, among which, the sleep disorder, constipation and fatigue had most significantly positive correlation with 5-HT or Trp, r-value was respectively 0.373, 0.233 and 0.563. CONCLUSIONS: Lead exposure not only causes the alteration of neuropsychiatric behavior of lead workers, but also changes gastrointestinal symptoms. Serotonin may be involved as the main neurotransmitter synthesized in intestinal, and the synthesis and metabolism may be regulated by intestinal flora.


Assuntos
Chumbo/sangue , Testes Neuropsicológicos , Neurotransmissores/sangue , Exposição Ocupacional/análise , Serotonina/sangue , Adulto , Estudos Transversais , Tontura/psicologia , Fadiga/psicologia , Feminino , Humanos , Chumbo/efeitos adversos , Masculino , Náusea/psicologia , Neurotransmissores/metabolismo , Exposição Ocupacional/efeitos adversos , Serotonina/metabolismo , Transtornos do Sono-Vigília/psicologia , Inquéritos e Questionários , Vômito/psicologia , Adulto Jovem
13.
Artigo em Inglês | MEDLINE | ID: mdl-33387860

RESUMO

A method for the simultaneous determination of aspartic acid (Asp), glutamic acid (Glu), glycine (Gly), taurine (Tau) and gamma-aminobutyric acid (GABA) in animal blood and brain by two-dimensional liquid chromatography (2D-LC) combined with ultraviolet detection was established for the first time. First, the amino acid neurotransmitters (AANTs) were labeled on the corresponding fluorescent derivatives with 4-fluoro-7-nitrobenzofurazan (NBD-F), enriched on the extraction column and automatically transferred to the analytical column to achieve on-line extraction and complete separation of the target components. This method exhibited good selectivity, and the correlation coefficients for the analyte calibration curves of were > 0.99. The intra- and inter-day precisions were ≤ 16.03, and the accuracies were in the range of 70.59-116.20%. The system realizes the rapid detection and stability quantification of the five AANTs, which proves that the alternative dilution method is feasible. The results show that the system has high loading capacity, excellent resolution, and good peak shape and is not affected by other endogenous substances. Moreover, the developed method has been successfully applied to the analysis of biological samples in the blood and whole brain of rats and pigs. The content of AANTs in the hippocampus and cortex of rats was higher than that in those of pigs. This method is expected to provide applicability for the determination of AANTs in pharmacological, pharmaceutical and clinical research in nervous science.


Assuntos
Aminoácidos/análise , Cromatografia Líquida de Alta Pressão/métodos , Neurotransmissores/análise , Ácido gama-Aminobutírico/análise , Aminoácidos/sangue , Aminoácidos/química , Animais , Química Encefálica , Limite de Detecção , Modelos Lineares , Neurotransmissores/sangue , Neurotransmissores/química , Ratos , Reprodutibilidade dos Testes , Suínos , Ácido gama-Aminobutírico/química
14.
Carbohydr Polym ; 256: 117418, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33483010

RESUMO

Constipation is one of the most prevalent gastrointestinal tract diseases. Konjac glucomannan (KGM) dietotherapy can effectively relieve the clinical symptoms of patients with constipation. However, the causal relationship among KGM, constipation and different gastrointestinal microbiome (i.e., the stomach {St}, small intestine {S}, and large intestine {L}) remains poorly understood. In this study, constipated mice were treated with KGM (75, 150, 300 mg/kg bw). Results showed that KGM treatment improved the general physiological state, fecal character, small intestinal propulsive rate, gastric emptying rate, MTL and AchE activities, ET-1, 5-HT, and NO levels, and SCFA concentrations. KGM in the diets of constipated mice reduced the diversity of St and S microbiota, while increased those in the L. The KGM intervention regulated the microbiota profile, which afterwards was closer to the normal mouse group: confirmation was provided by different changes of bacteria like Lactobacillus, Bifidobacterium and Allobaculum spp et al.


Assuntos
Constipação Intestinal/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Loperamida/efeitos adversos , Mananas/farmacologia , Ração Animal , Animais , Bactérias , Bifidobacterium , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/dietoterapia , DNA/análise , Fezes , Feminino , Glicosídeos/química , Lactobacillus , Mananas/química , Manose/química , Camundongos , Neurotransmissores/sangue , Polímeros/química , Probabilidade , Solubilidade
15.
Ultrason Sonochem ; 70: 105305, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33126185

RESUMO

The binary nanomaterials and graphitic carbon based hybrid has been developed as an important porous nanomaterial for fabricating electrode with applications in non-enzymatic (bio) sensors. We report a fast synthesis of bimetal oxide particles of nano-sized manganese ferrite (MnFe2O4) decorated on graphitic carbon nitride (GCN) via a high-intensity ultrasonic irradiation method for C (30 kHz and 70 W/cm2). The nanocomposites were analyzed by powder X-ray diffraction, XPS, EDS, TEM to ascertain the effects of synthesis parameters on structure, and morphology. The MnFe2O4/GCN modified electrode demonstrated superior electrocatalytic activity toward the neurotransmitter (5-hydroxytryptamine) detection with a high peak intensity at +0.21 V. The appealing application of the MnFe2O4/GCN/GCE as neurotransmitter sensors is presented and a possible sensing mechanism is analyzed. The constructed electrochemical sensor for the detection of 5-hydroxytryptamine (STN) showed a wide working range (0.1-522.6 µM), high sensitivity (19.377 µA µM-1 cm-2), and nano-molar detection limit (3.1 nM). Moreover, it is worth noting that the MnFe2O4/GCN not only enhanced activity and also promoted the electron transfer rate towards STN detection. The proposed sensor was analyzed for its real-time applications to the detection of STN in rat brain serum, and human blood serum in good satisfactory results was obtained. The results showed promising reproducibility, repeatability, and high stability for neurotransmitter detection in biological samples.


Assuntos
Técnicas Eletroquímicas/métodos , Compostos Férricos/química , Química Verde , Compostos de Manganês/química , Neurotransmissores/metabolismo , Nitrilas/química , Sonicação/métodos , Animais , Encéfalo/metabolismo , Catálise , Humanos , Limite de Detecção , Neurotransmissores/sangue , Ratos , Difração de Raios X
16.
J Vet Intern Med ; 35(6): 2596-2606, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34599615

RESUMO

BACKGROUND: The neurotransmitter serotonin (5-HT) affects valvular degeneration and dogs with myxomatous mitral valve disease (MMVD) exhibit alterations in 5-HT signaling. In Maltese dogs, 3 single nucleotide polymorphisms (SNPs) in the 5-HT transporter (SERT) gene are suggested to associate with MMVD. HYPOTHESIS/OBJECTIVES: Determine the association of SERT polymorphisms on MMVD severity and serum 5-HT concentration in Cavalier King Charles Spaniels (CKCS). Additionally, investigate the association between selected clinical and hematologic variables and serum 5-HT and assess the correlation between HPLC and ELISA measurements of serum 5-HT. ANIMALS: Seventy-one CKCS (42 females and 29 males; 7.8 [4.7;9.9] years (median [Q1;Q3])) in different MMVD stages. METHODS: This prospective study used TaqMan genotyping assays to assess SERT gene polymorphisms. Neurotransmitter concentrations were assessed by HPLC and ELISA. RESULTS: TaqMan analyses identified none of the selected SERT polymorphisms in any of the CKCS examined. Serum 5-HT was associated with platelet count (P < .001) but not MMVD severity, age or medical therapy and did not correlate with serum concentration of the 5-HT metabolite, 5-hydroxyindoleacetic acid. The ELISA serum 5-HT correlated with HPLC measurements (ρ = .87; P < .0001) but was lower (mean difference = -22 ng/mL; P = .02) independent of serum 5-HT concentration (P = .2). CONCLUSIONS AND CLINICAL IMPORTANCE: Selected SERT SNPs associated with MMVD in Maltese dogs were not found in CKCS and only platelet count influenced serum 5-HT concentration. These SNPs are unlikely to be associated with MMVD pathophysiology or serum 5-HT concentration in CKCS. HPLC and ELISA serum 5-HT demonstrated good correlation but ELISA systematically underestimated 5-HT.


Assuntos
Doenças do Cão , Valva Mitral , Neurotransmissores/sangue , Proteínas da Membrana Plasmática de Transporte de Serotonina , Animais , Doenças do Cão/genética , Cães/genética , Feminino , Masculino , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética
17.
Nutrients ; 12(12)2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33256231

RESUMO

Mustard leaf (Brassica juncea var. crispifolia L. H. Bailey) has been reported to have psychological properties such as anti-depressant activities. However, studies on chronic stress and depression caused by restraint have not been conducted. Therefore, this study aimed to evaluate the effects of a mustard leaf (ML) extract on chronic restraint stress (CRS) in mice. Male mice were subjected to a CRS protocol for a period of four weeks to induce stress. The results showed that the ML extract (100 and 500 mg/kg/perorally administered for four weeks) significantly decreased corticosterone levels and increased neurotransmitters levels in stressed mice. Apoptosis by CRS exposure was induced by Bcl-2 and Bax expression regulation and was suppressed by reducing caspase-3 and poly (ADP-ribose) polymerase expression after treatment with the ML extract. Our results confirmed that apoptosis was regulated by increased expression of brain-derived neurotrophic factor (BDNF). Additionally, cytokine levels were regulated by the ML extract. In conclusion, our results showed that the ML extract relieved stress effects by regulating hormones and neurotransmitters in CRS mice, BDNF expression, and apoptosis in the brain. Thus, it can be suggested that the studied ML extract is an agonist that can help relieve stress and depression.


Assuntos
Apoptose/efeitos dos fármacos , Corticosterona/sangue , Mostardeira , Neurotransmissores/sangue , Extratos Vegetais/farmacologia , Restrição Física/psicologia , Estresse Psicológico/tratamento farmacológico , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/sangue , Estresse Psicológico/sangue
18.
Nutrients ; 12(10)2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33053828

RESUMO

Citicoline is a chemical compound involved in the synthesis of cell membranes. It also has other, not yet explained functions. Research on the use of citicoline is conducted in neurology, ophthalmology, and psychiatry. Citicoline is widely available as a dietary supplement. It is often used to enhance cognitive functions. In our article, accessible databases were searched for articles regarding citicoline use in neurological diseases. This article has a systemic review form. After rejecting non-eligible reports, 47 remaining articles were reviewed. The review found that citicoline has been proven to be a useful compound in preventing dementia progression. It also enhances cognitive functions among healthy individuals and improves prognosis after stroke. In an animal model of nerve damage and neuropathy, citicoline stimulated regeneration and lessened pain. Among patients who underwent brain trauma, citicoline has an unclear clinical effect. Citicoline has a wide range of effects and could be an essential substance in the treatment of many neurological diseases. Its positive impact on learning and cognitive functions among the healthy population is also worth noting.


Assuntos
Citidina Difosfato Colina/farmacologia , Doenças do Sistema Nervoso/tratamento farmacológico , Animais , Lesões Encefálicas Traumáticas/tratamento farmacológico , Cognição/efeitos dos fármacos , Demência/prevenção & controle , Modelos Animais de Doenças , Humanos , Metanálise como Assunto , Neuralgia/tratamento farmacológico , Neurotransmissores/sangue , Sistema Nervoso Periférico/efeitos dos fármacos , Sistema Nervoso Periférico/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico
19.
J Sep Sci ; 43(21): 4006-4017, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32866349

RESUMO

In this study, an efficient and sensitive assay for the detection of 42 polar neurochemicals, including neurotransmitters, amino acids, and biogenic amines, was established by combining reversed-phase liquid chromatography tandem mass spectrometry with chemical derivatization. An optimally designed benzoyl chloride derivatization was easily conducted in a one-pot reaction and stable neurochemical derivatives were obtained under mild conditions within 5 min (except for acetylcholine and melatonin). Derivatization also enabled the introduction of heavy labeling of the analytes through the use of labeled derivatization agents. Chromatography separation was performed on an HSS T3 column within 15 min by gradient elution. Multiple reaction monitoring acquisition mode enabled quantitation of neurochemicals with limits of detection of 0.05 to 11.63 nM and lower limits of quantitation of 0.09 to 46.50 nM in rat serum. The assay was well validated in terms of linearity and extraction recovery. Furthermore, the instrumental precision, specificity, matrix effect, accuracy, precision, stability, dilution effect, and carry-over effect were also validated. Finally, the overall efficacy of the assay was experimentally tested using serum from six Sprague-Dawley rats. The results demonstrated that the developed method is effective for broad targeted analysis of 42 neurochemicals in serum.


Assuntos
Neurotransmissores/sangue , Animais , Cromatografia Líquida de Alta Pressão , Masculino , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
20.
Int J Biol Macromol ; 164: 4231-4244, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32918960

RESUMO

During the last few decades, there has been evident growth in the development and fabrication of nano structured materials due to their wide application for different fields of material science and engineering. Among all these materials, natural polymer-based hydrogels such as polysaccharides, proteins, lipids etc. are gaining significant attention in the field of nanotechnology. Among them Chitosan hydrogels are widely used. These are cross-linked hydrophilic polymers which facilitate the uptake of significant quantity of water without being dissolved in water. They are hydrophilic in nature antimicrobial mainly need for fabrication of novel biomaterial These are chemically and physically firm, soft, stretchy polymeric network, reusable and multi-functional in nature. Chitosan has extensive properties including electrical, photo thermal characteristics, catalysis, anti-microbial characteristics, drug degradation, pollutants removal; bio-sensing etc. make it ultimate for "smart" nanostructure material. Recently, advance in the applications of Chitosan has made it an appreciable research material among the researchers. In this review we will focus on properties and applications of Chitosan as smart material in sensor configurations in various fields like clinical and environmental analysis.


Assuntos
Técnicas Biossensoriais , Quitosana/química , Técnicas Eletroquímicas , Animais , Antioxidantes , Materiais Biocompatíveis/química , Biomarcadores , Glicemia , Quitosana/isolamento & purificação , Humanos , Metais Pesados , Nanoestruturas/química , Nanotecnologia , Neurotransmissores/sangue
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