Different Doses of Dexmedetomidine Reduce Postoperative Sleep Disturbance Incidence in Patients under General Anesthesia by Elevating Serum Neurotransmitter Levels.

Postoperative sleep disturbance is a common issue that affects recovery in patients undergoing general anesthesia. Dexmedetomidine (Dex) has a potential role in improving postoperative sleep quality. We evaluated the effects of different doses of Dex on postoperative sleep disturbance and serum neurotransmitters in patients undergoing radical gastrectomy under general anesthesia. Patients were assigned to the control, NS, and Dex (Dex-L/M/H) groups based on different treatment doses [0.2, 0.4, and 0.6 µg/(kg · h)]. The Athens Insomnia Scale (AIS) and ELISA kits were used to assess sleep disturbance and serum neurotransmitter (GABA, 5-HT, NE) levels before surgery and on postoperative days one, four, and seven. The effects of different doses on postoperative sleep disturbance incidence and serum neurotransmitter levels were analyzed by the Fisher exact test and one-way and repeated-measures ANOVA. Patients had no differences in gender, age, body mass index, operation time, and bleeding volume. Different Dex doses reduced the postoperative AIS score of patients under general anesthesia, improved their sleep, and increased serum levels of 5-HT, NE, and GABA. Furthermore, the effects were dose-dependent within the range of safe clinical use. Specifically, Dex at doses of 0.2, 0.4, and 0.6 µg/(kg · h) reduced postoperative AIS score, elevated serum neurotransmitter levels, and reduced postoperative sleep disturbance incidence. Collectively, Dex has a potential preventive effect on postoperative sleep disturbance in patients undergoing general anesthesia for radical gastrectomy. The optimal dose of Dex is between 0.2 and 0.6 µg/(kg · h), which significantly reduces the incidence of postoperative sleep disturbance and increases serum neurotransmitter levels.

Endocannabinoid levels in plasma and neurotransmitters in the brain: a preliminary report on patients with a psychotic disorder and healthy individuals.

BACKGROUND: Interactions between the endocannabinoid system (ECS) and neurotransmitter systems might mediate the risk of developing a schizophrenia spectrum disorder (SSD). Consequently, we investigated in patients with SSD and healthy controls (HC) the relations between (1) plasma concentrations of two prototypical endocannabinoids (N-arachidonoylethanolamine [anandamide] and 2-arachidonoylglycerol [2-AG]) and (2) striatal dopamine synthesis capacity (DSC), and glutamate and y-aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC). As anandamide and 2-AG might reduce the activity of these neurotransmitters, we hypothesized negative correlations between their plasma levels and the abovementioned neurotransmitters in both groups. METHODS: Blood samples were obtained from 18 patients and 16 HC to measure anandamide and 2-AG plasma concentrations. For all subjects, we acquired proton magnetic resonance spectroscopy scans to assess Glx (i.e. glutamate plus glutamine) and GABA + (i.e. GABA plus macromolecules) concentrations in the ACC. Ten patients and 14 HC also underwent [18F]F-DOPA positron emission tomography for assessment of striatal DSC. Multiple linear regression analyses were used to investigate the relations between the outcome measures. RESULTS: A negative association between 2-AG plasma concentration and ACC Glx concentration was found in patients (p = 0.008). We found no evidence of other significant relationships between 2-AG or anandamide plasma concentrations and dopaminergic, glutamatergic, or GABAergic measures in either group. CONCLUSIONS: Our preliminary results suggest an association between peripheral 2-AG and ACC Glx levels in patients.

Effect of esketamine on serum neurotransmitters in patients with postpartum depression: a randomized controlled trial.

BACKGROUND: The development of postpartum depression has been linked to fluctuations in the levels of neurotransmitters in the human body, such as 5-hydroxytryptamine (5-HT), dopamine (DA), noradrenaline (Norepinephrine, NE), and brain derived neurotrophic factor (BDNF). Research has indicated that the antidepressant effect of esketamine are mediated by monoamine transmitters and neurotrophic factors. Therefore, we postulate that intravenous administration of esketamine in patients with postpartum depression may alter the serum concentrations of these neurotransmitters. METHODS: Three hundred fifteen patients with postpartum depression were selected and divided into two groups based on randomized numerical expression: esketamine (E) group (0. 25 mg/kg esketamine) and control (C) group (a same volume of 0.9% saline), all the drugs were pumped for 40 min. After the end of drug pumping, all patients were continuously observed for 2 h. Changes in serum levels of 5-HT, DA, NE, BDNF were recorded before drug administration and on the 3rd day after drug administration. The scores of Edinburgh Postnatal Depression Scale (EPDS) were calculated before drug administration, and on the 3rd day and on the 30th day after drug administration. Dizziness, headache, nausea, vomiting, drowsiness, and feeling of detachment occurred were recorded within 2 h after drug administration. RESULTS: Before drug administration, the serum concentrations of 5-HT,DA,BDNF,NE in Group E and Group C were namely (0. 91 ± 0. 19 vs. 0. 98 ± 0. 21, P = 0. 181), (2. 38 ± 0. 35 vs. 2. 32 ± 0. 32, P = 0. 491), (3. 07 ± 0. 89 vs 3. 02 ± 0. 88, P = 0. 828), (39. 79 ± 7. 78 vs 41. 34 ± 10. 03, P = 0. 506). On the third day post-medication, the serum concentrations of 5-HT,DA,BDNF,NE in Group E and Group C were namely (1. 42 ± 0. 35 vs. 0. 96 ± 0. 24, P < 0. 001), (3. 99 ± 0. 17 vs. 2. 41 ± 0. 28, P < 0. 001),(5. 45 ± 0. 81 vs 3. 22 ± 0. 76, P < 0. 001),(44. 36 ± 9. 98 vs 40. 69 ± 11. 75, P = 0. 198). Before medication, the EPDS scores were (16. 15 ± 3. 02 vs 17. 85 ± 3. 89, P = 0. 064). on the third day after medication, the Group E had significantly reduced scores (12. 98 ± 2. 39 vs 16. 73 ± 3. 52, P < 0. 001). On the 30rd day after medication, EPDS scores between the two groups were (16. 34 ± 3. 43 vs 16. 91 ± 4. 02, p = 0. 203). Within 2 h of medication, the rate of adverse events was similar between the two groups. CONCLUSIONS: Small doses of esketamine can increase the serum concentration of 5-HT,DA,BDNF, and in the short term, decrease EPDS scores, and improve postpartum depressive symptoms. TRIAL REGISTRATION: Retrospectively registered in the Chinese Clinical Trial Registry (ChiCTR2300078343, 2023/12/05).

Correlation between Neurotransmitters (Dopamine, Epinephrine, Norepinephrine, Serotonin), Prognostic Nutritional Index, Glasgow Prognostic Score, Systemic Inflammatory Response Markers, and TNM Staging in a Cohort of Colorectal Neuroendocrine Tumor Patients.

Neuroendocrine tumors are uncommon in the gastrointestinal system but can develop in the majority of the body's epithelial organs. Our goal was to examine the presence and clinical application of serum dopamine (DA), serotonin (ST), norepinephrine (NE), and epinephrine (EPI), in addition to determining the significance of the Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), and systemic inflammatory response (SIR) markers as a prognostic factor for patients with colorectal neuroendocrine tumors (CR-NETs), in various tumor-node-metastasis (TNM) stages. We also wanted to identify the possible connection between them. This study included 25 consecutive patients who were diagnosed with CR-NETs and a control group consisting of 60 patients with newly diagnosed colorectal cancer (CRC). We used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. This study revealed that CR-NET patients showed significantly higher serum levels of DA compared to CRC patients. We showed that serum DA was present in the early stages of CR-NETs, with increasing levels as we advanced through the TNM stages. Moreover, we found a close relationship between the levels of DA and the inflammation and nutritional status of the CR-NET patients in this study. CR-NET patients from the PNI < 47.00 subgroup had a higher level of DA than those from the PNI ≥ 47.00 subgroup. Pearson's correlation analysis revealed correlations between DA, PNI, and the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR). Both hematological indices were negatively correlated with albumin (ALB). Our investigation's findings relating to the PNI, GPS, SIR, and DA indicate that these tools can be markers of nutritional and systemic inflammatory status, are simple to use, and are repeatable. Further research on this topic could provide valuable insights into which biomarkers to incorporate into clinical practice for the management of CR-NET patients.

The Complex Relationship between Neuromodulators, Circadian Rhythms, and Insomnia in Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) has been linked to disruptions in circadian rhythm and neurotrophin (NFT) signaling. This study explored the link between neuromodulators, chronotype, and insomnia in OSA. The participants (n = 166) underwent polysomnography (PSG) before being categorized into either the control or the OSA group. The following questionnaires were completed: Insomnia Severity Index (ISI), Epworth Sleepiness Scale, Chronotype Questionnaire (morningness-eveningness (ME), and subjective amplitude (AM). Blood samples were collected post-PSG for protein level assessment using ELISA kits for brain-derived neurotrophic factor (BDNF), proBDNF, glial-cell-line-derived neurotrophic factor, NFT3, and NFT4. Gene expression was analyzed utilizing qRT-PCR. No significant differences were found in neuromodulator levels between OSA patients and controls. The controls with insomnia exhibited elevated neuromodulator gene expression (p < 0.05). In the non-insomnia individuals, BDNF and NTF3 expression was increased in the OSA group compared to controls (p = 0.007 for both); there were no significant differences between the insomnia groups. The ISI scores positively correlated with all gene expressions in both groups, except for NTF4 in OSA (R = 0.127, p = 0.172). AM and ME were predicting factors for the ISI score and clinically significant insomnia (p < 0.05 for both groups). Compromised compensatory mechanisms in OSA may exacerbate insomnia. The correlation between chronotype and NFT expression highlights the role of circadian misalignments in sleep disruptions.

Regulation of gut microbiota and serum neurotransmitters in mice by Streptococcus thermophilus GA8- and Lacticaseibacillus rhamnosus HAO9-fermented milk containing high levels of gamma-aminobutyric acid.

BACKGROUND: Gamma-aminobutyric acid (GABA) is an important neurotransmitter in the human body, with several negative emotions reported as being associated with GABA dysregulation. This study investigates the safety and modulatory effects of GABA-enriched milk, fermented by Streptococcus thermophilus GA8 and Lacticasebacillus rhamnosus HAO9, on the gut microbiota and neurotransmitter profiles in mice. RESULTS: Through rigorous culturing and fermentation processes, we achieved consistent GABA production in milk, with concentrations reaching 4.6 and 8.5 g L-1 for GA8-fermented and co-fermented milk, respectively, after 48 h. Using SPF male C57BL/6J mice, we administered either mono-culture or combined-culture milk treatments and monitored physiological impacts. The treatments did not affect mouse body weight but induced significant changes in gut microbiota composition. Beta diversity analysis revealed distinct microbial profiles between treatment groups, highlighting fermentation-specific microbial shifts, such as an increase in Verrucomicrobia for the GA8 group and a modulation in Saccharibacteria_genera_incertae_sedis for the GA8 + HAO9 group. Serum neurotransmitter levels were elevated in both treatment groups, with significant increases in l-glutamine, l-tryptophan and, notably, serotonin hydrochloride in the GA8 + HAO9 group. Correlation analysis identified a positive association between specific bacterial genera and neurotransmitter levels, suggesting a probiotic effect on neuroactive substances. CONCLUSION: These findings suggest that fermented milk has potential as a probiotic supplement for mood improvement and stress relief, highlighting its role in modulating the gut-brain axis. © 2024 Society of Chemical Industry.

Impact of sleep patterns upon female neuroendocrinology and reproductive outcomes: a comprehensive review.

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.

The effect and mechanism of Jiao-tai-wan in the treatment of diabetes mellitus with depression based on network pharmacology and experimental analysis.

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.

Detection of 3-O-methyldopa in dried blood spots for neonatal diagnosis of aromatic L-amino-acid decarboxylase deficiency: The northeastern Italian experience.

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.

Murexide-derived in vitro electrochemical sensor for the simultaneous determination of neurochemicals.

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.

The variation in the levels of 18 amino acids in the cortex and plasma of cerebral ischemia C57BL/6 mice.

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.

Determination of monoamine neurotransmitters and metabolites by high-performance liquid chromatography based on Ag(III) complex chemiluminescence detection.

A novel, simple and efficient chemiluminescence system has been developed for the determination of monoamine neurotransmitters and metabolites. By using the Ag (III)-luminol chemiluminescence system as a detector, a high performance liquid chromatography chemiluminescence method (HPLC-CL) was established and used to detect seven monoamine neurotransmitters. Under the optimized conditions, the detection limits (3S/N) of epinephrine (E), levodopa (l-DOPA), dopamine (DA), serotonin (5-HT), 3-methoxy-4-hydroxyphenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxypentylacetic acid (5-HIAA) were 20.0 µg dm-3,15.0 µg dm-3, 15.0 µg dm-3, 8.0 µg dm-3, 2.0 µg dm-3, 2.0 µg dm-3 and 3.0 µg dm-3, respectively. Moreover, they were well within the linear range of 50-1000 µg dm-3, 50-1000 µg dm-3, 50-1000 µg dm-3, 25-1000 µg dm-3, 5-25 µg dm-3, 5-25 µg dm-3 and 10-30 µg dm-3, respectively. The average recovery varied between 84.82% and 110.4%. The method has the attributes of simplicity, high sensitivity, and high efficiency. The sensitization and inhibition mechanisms for luminol-[Ag(HIO6)2]5-- analytes CL system were proposed by CL spectra and free-radical capture experiment.

Biomarker study of the biological parameter and neurotransmitter levels in autistics.

Autism is a prevalent developmental disorder that combines repetitive behaviours, social deficits and language abnormalities. The present study aims to assess the autistic subjects using DSM IV-TR criteria followed with the analysis of neurotransmitters, biochemical parameters, oxidative stress and its ions in two groups of autistic subjects (group I < 12 years; group II ≥ 12 years). Antioxidants show a variation of 10% increase in controls compared to autistic age < 12 years. The concentration of pyruvate kinase and hexokinase is elevated in controls approximately 60% and 45%, respectively, with the significance of 95 and 99%. Autistic subjects showed marked variation in levels of neurotransmitters, oxidative stress and its related ions. Cumulative assessment of parameters related to biochemical markers and neurotransmitters paves the way for autism-based research, although these observations draw interest in an integrated approach for autism.

Mortality in cardiogenic shock is stronger associated to clinical factors than contemporary biomarkers reflecting neurohormonal stress and inflammatory activation.

PURPOSE: To validate the IABP-SHOCK II risk score in a Danish cohort and assess the association between the IABP-SHOCK II risk score and admission concentration of biomarkers reflecting neurohormonal - (Copeptin, Pro-atrial natriuretic peptide (proANP), Mid-regional pro-adrenomedullin (MRproADM)) and inflammatory (ST2) activation in patients with CS complicating ST segment elevation myocardial infarction (STEMI). METHODS: A total of 137 consecutive patients admitted with STEMI and CS at two tertiary heart centres were stratified according to the IABP-SHOCK II risk score (0-2; 3/4; 5-9), and had blood sampled upon admission. RESULTS: Plasma concentrations of Copeptin (median (pmol/L) score 0-2: 313; score 3/4: 682; score 5-9: 632 p < 0.0001), proANP (pmol/L) (1459; 2225; 2876 p = 0.0009) and MRproADM (nmol/L) (0.86; 1.2; 1.4 p = 0.04) were significantly associated with the risk score, whereas ST2 (ng/mL) was not (44; 60; 45 p = 0.23). The IABP-SHOCK II risk score predicted 30-day mortality (score 0-2: 22%; score 4/3: 51%; score 5-9: 72%, area under the curve (AUC): 0.73, plogrank < 0.0001), while the tested biomarkers did not (AUC: 0.51

Regulating the Enteric Nervous System against Obesity in Mice by Electroacupuncture.

BACKGROUND AND OBJECTIVES: The enteric nervous system (ENS) dominates the onset of obesity and has been shown to regulate nutrient absorption and energy metabolism. METHODS AND STUDY DESIGN: This study was performed to investigate the role of electroacupuncture in regulating ENS function in obese mice. Obese mice were obtained by high-fat diet. 16S rRNA pyrosequencing, Western blotting, quantitative PCR, and neurotransmitter analysis were used for this purpose. RESULTS: Body weight, Lee index, serum lipid, leptin, and adiponectin levels, and other basic indices were significantly ameliorated after electroacupuncture intervention. The pathological ENS scores, serum neurotransmitter levels, and intestinal transit rate were markedly changed in obese mice. Moreover, electroacupuncture promoted the diversity of gut microbiota. No significant differences were observed 21 and 28 days after electroacupuncture. CONCLUSIONS: These results suggested ENS may be a new treatment approach to obesity.

Highly Stable Lanthanide Metal-Organic Framework as an Internal Calibrated Luminescent Sensor for Glutamic Acid, a Neuropathy Biomarker.

Glutamic acid (Glu) is the most abundant excitatory neurotransmitter in the central nervous system, and an elevated level of Glu may indicate some neuropathological diseases. Herein, three isomorphic microporous lanthanide metal-organic frameworks (MOFs) [(CH3)2NH2]2[Ln6(µ3-OH)8(BDC-OH)6(H2O)6]·(solv)x (ZJU-168; ZJU = Zhejiang University, H2BDC-OH = 2-hydroxyterephthalic acid, Ln = Eu, Tb, Gd) were designed for the detection of Glu. ZJU-168(Eu) and ZJU-168(Tb) suspensions simultaneously produce the characteristic emission bands of both lanthanide ions and ligands. When ZJU-168(Eu) and ZJU-168(Tb) suspensions exposed to Glu, the fluorescence intensity of ligands increases while the emission of lanthanide ions is almost unchanged. By utilizing the emission of ligands as the detected signal and the emission of lanthanide ions as the internal reference, an internal calibrated fluorescence sensor for Glu was obtained. There is a good linear relationship between fluorescence intensity ratio and Glu concentration in a wide range with the detection limit of 3.6 µM for ZJU-168(Tb) and 4.3 µM for ZJU-168(Eu). Major compounds present in blood plasma have no interference for the detection of Glu. Furthermore, a convenient analytical device based on a one-to-two logic gate was constructed for monitoring Glu. These establish ZJU-168(Tb) as a potential turn-on, ratiometric, and colorimetric fluorescent sensor for practical detection of Glu.

Identification of markers of depression and neurotoxicity in pesticide exposed agriculture workers.

Earlier, we reported that chronic exposure to pesticides causes a reduction in the acetylcholinesterase activity and hematological and biochemical alterations in agriculture workers. In continuation with that, the present study aimed to investigate the pesticide-induced neurochemical imbalance and its association with behavior alterations in agricultural workers. A significant increase in depressive symptoms, assessed by the Beck Depression Inventory-II was observed in pesticide exposed workers as compared to the unexposed. A decrease in the level of dopamine in plasma and levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acids, norepinephrine, serotonin, and hydroxyindoleacetic acid in urine was also observed. An increase in the levels of MAO-A and MAO-B has also been observed in these individuals. The decreased levels of neurotransmitters in the blood and urine have been linked with increased levels of MAO and pesticide residues in plasma and urine. Furthermore, these changes were associated with a higher incidence of depression in agricultural workers.

Serum levels of glial cell line-derived neurotrophic factor and multiple neurotransmitters: In relation to cognitive performance in Parkinson's disease with mild cognitive impairment.

OBJECTIVES: Mild cognitive impairment is a common non-motor feature of Parkinson's disease, termed PD-MCI. But there is a scarcity of data on the role of glial cell line-derived neurotrophic factor (GDNF) and neurotransmitters in pathogenesis of PD-MCI. The aim of this project was to detect the serum levels of GDNF and multiple neurotranmitters and explore their relationships with cognitive performance in PD-MCI patients. METHODS: Neuropsychological testing was administered to PD patients and healthy controls to investigate different domains of cognitive function. Serum levels of GDNF and four cognition-related neurotransmitters including Dopamine metabolites Homovanillic acid (HVA), acetylcholine (Ach), γ-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT) were detected by enzyme-linked immunosorbent assay and liquid chromatography-electrospray ionization tandem mass spectrometry analysis respectively. RESULTS: The more serious cognitive impairment of PD, the lower levels of GDNF, HVA and 5-HT. In PD-MCI patients, the levels of GDNF, HVA, Ach, 5-HT, and GABA had a significant positive correlation with Digit span backward test (DSB-T) scores and negative correlation with the scores of Trail Making Test A (TMT-A) and Trail Making Test B (TMT-B) respectively. Effect size analysis showed that GDNF and GDNF*Ach have a significant effect on DSB-T, TMT-A and TMT-B respectively; GDNF*HVA, GDNF*5-HT and GDNF*GABA play important part in Auditory Verbal Learning Test separately. CONCLUSIONS: Serum GDNF may be involved in the impairment of attention, memory and executive function of PD-MCI patients, by acting alone or in conjunction with neurotransmitters (HVA, 5-HT, GABA, and Ach).

Broad targeted analysis of neurochemicals in rat serum using liquid chromatography tandem mass spectrometry with chemical derivatization.

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.

Enzyme-Free Plasmonic Biosensor for Direct Detection of Neurotransmitter Dopamine from Whole Blood.

Complex biological fluids without pretreatment, separation, or purification impose stringent limitations on the practical deployment of label-free plasmonic biosensors for advanced assays needed in point of care applications. In this work, we present an enzyme-free plasmonic neurotransmitter dopamine biosensor integrated with a microfluidic plasma separator. This integrated device allows the in-line separation of plasma directly from the bloodstream and channels it to the active detection area, where inorganic cerium oxide nanoparticles function as local selective dopamine binding sites through strong surface redox reaction. A thorough understanding and engineering of the nanoparticles is carried out to maximize its dopamine sensitivity and selectivity. We obtain detection of dopamine at 100 fM concentration in simulated body fluid and 1 nM directly from blood without any prior sample preparation. The detection selectivity is found to be at least five-times higher compared to the common interfering species. This demonstration shows the feasibility of the practical implementation of the proposed plasmonic system in detection of variety of biomarkers directly from the complex biological fluids.