Serum Glutamate Levels Research Articles

Baseline serum glutamate: Implications for diagnosis and prediction in mild cognitive impairment and Alzheimer’s disease of the Alzheimer’s Disease Neuroimaging Initiative

PurposeNumerous studies have highlighted a close link between metabolic imbalances and Alzheimer’s Disease (AD). The advancement of metabolomics has recently enabled the exploration of characteristic metabolic changes associated with AD. Studies indicate that serum glutamate (Glu) levels may correlate with mild cognitive impairment (MCI) and AD. This study aims to further elucidate the characteristics of baseline serum Glu levels in MCI and AD. MethodsThis study included 783 participants from the Alzheimer’s Disease Neuroimaging Initiative-1 (ADNI-1) cohort, categorized into cognitively normal (CN, n = 224), stable MCI (sMCI, n = 181), progressive MCI (pMCI, n = 193), and AD (n = 185). The study aimed to analyze the diagnostic value of baseline serum Glu, to explore its predictive capability for the progression from CN to MCI or AD, and from MCI to AD, and to analyze the relationship between serum Glu and cerebrospinal fluid (CSF) biomarkers and cognitive functions in different diagnostic groups. ResultsCompared to the CN and sMCI groups, the pMCI group showed significantly lower levels of serum Glu, and the AD group also had lower Glu levels compared to the sMCI group. However, serum Glu did not show significant diagnostic value for MCI and AD. Lower levels of serum Glu could predict the progression from MCI to AD. ConclusionSerum Glu levels can predict the progression from MCI to AD, suggesting that it could provide new insights into the pathophysiological mechanisms of AD. However, serum Glu may not be an ideal peripheral biomarker for AD.

Effects of integrative therapy with Du Meridian moxibustion, ear acupuncture, and alprazolam on cardiac function and neurotransmitter levels in patients with coronary heart disease and insomnia: An observational study.

To explore the effects of Du Meridian moxibustion combined with ear acupuncture on clinical symptoms and serum neurotransmitters in patients with coronary heart disease and insomnia. This study is a retrospective study. From June 2021 to May 2023, 116 patients with coronary heart disease and insomnia treated at our hospital were selected as subjects. They were divided into 2 groups according to the treatment. The control group received treatment with alprazolam, while the experimental group received Du Meridian moxibustion combined with ear acupuncture in addition to alprazolam treatment. The efficacy of the 2 groups was compared, and the levels of cardiac function indicators, serum melatonin, leptin, and neurotransmitters were measured. The total effectiveness rate in the experimental group was 93.10% (with a cure rate of 36.21%, a significant improvement rate of 41.38%, and an effective rate of 15.52%), which was significantly higher than the 79.31% in the control group (with a cure rate of 24.14%, a significant improvement rate of 32.76%, and an effective rate of 22.41%) (P < .05). Both groups exhibited an increase in left ventricular ejection fraction, stroke volume, and cardiac output after treatment compared to before treatment. Additionally, left ventricular end-systolic diameter decreased after treatment compared to before treatment, but the cardiac function was compared between the 2 groups after treatment (P > .05). In both groups, serum melatonin and serotonin (5-HT) levels increased after treatment compared to before treatment, while serum leptin, dopamine, and glutamate levels decreased after treatment compared to before treatment. Furthermore, the experimental group had higher serum melatonin, 5-HT, and gamma-aminobutyric acid levels compared to the control group, and lower serum leptin, dopamine, and glutamate levels compared to the control group (P < .05). The serum traditional Chinese medicine syndrome score and Pittsburgh sleep quality index score of the 2 groups decreased after treatment, and the experimental group was lower than the conventional group (P < .05). The combination of Du Meridian acupuncture with ear acupuncture in the treatment of insomnia in coronary heart disease can regulate the expression of serum melatonin, leptin, and neurotransmitters, alleviate symptoms, and improve therapeutic efficacy.

Precision Medicine for Blood Glutamate Grabbing in Ischemic Stroke.

Glutamate grabbers, such as glutamate oxaloacetate transaminase (GOT), have been proposed to prevent excitotoxicity secondary to high glutamate levels in stroke patients. However, the efficacy of blood glutamate grabbing by GOT could be dependent on the extent and severity of the disruption of the blood-brain barrier (BBB). Our purpose was to analyze the relationship between GOT and glutamate concentration with the patient's functional status differentially according to BBB serum markers (soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and leukoaraiosis based on neuroimaging). This retrospective observational study includes 906 ischemic stroke patients. We studied the presence of leukoaraiosis and the serum levels of glutamate, GOT, and sTWEAK in blood samples. Functional outcome was assessed using the modified Rankin Scale (mRS) at 3 months. A significant negative correlation between GOT and glutamate levels at admission was shown in those patients with sTWEAK levels > 2900 pg/mL (Pearson's correlation coefficient: -0.249; p < 0.0001). This correlation was also observed in patients with and without leukoaraiosis (Pearson's correlation coefficients: -0.299; p < 0.001 vs. -0.116; p = 0.024). The logistic regression model confirmed the association of higher levels of GOT with lower odds of poor outcome at 3 months when sTWEAK levels were >2900 pg/mL (OR: 0.41; CI 95%: 0.28-0.68; p < 0.0001) or with leukoaraiosis (OR: 0.75; CI 95%: 0.69-0.82; p < 0.0001). GOT levels are associated with glutamate levels and functional outcomes at 3 months, but only in those patients with leukoaraiosis and elevated sTWEAK levels. Consequently, therapies targeting glutamate grabbing might be more effective in patients with BBB dysfunction.

Riboflavin Increases Serum Glutamine Levels in Rats with Streptozotocin-induced Diabetes

Diabetes mellitus is one of the most common chronic diseases in the world. Metabolomic studies have demonstrated altered blood levels of glutamate and glutamine during type 1 diabetes and type 2 diabetes. Riboflavin is a precursor of flavin adenine dinucleotide and flavin mononucleotide, which are coenzymes necessary for the function of enzymes involved in various biochemical reactions, including those affecting amino acid metabolism. In this study, we investigated the effects of riboflavin on serum glutamate and glutamine levels in rats with streptozotocin-induced type 1 diabetes. Diabetic rats received riboflavin (25 mg, 50 mg, or 100 mg) dissolved in the drinking water daily for 2 weeks. Our results showed that riboflavin supplementation did not affect serum glutamate levels but increased serum glutamine levels in diabetic rats. We speculate that increased serum glutamine levels resulting from riboflavin supplementation may have beneficial effects during diabetes.

Functional Connectivity Alterations and Molecular Characterization of the Anterior Cingulate Cortex in Tinnitus Pathology without Hearing Loss.

Compared with individuals with hearing loss, tinnitus patients without hearing loss have more psychological or emotional problems. Tinnitus is closely associated to abnormal metabolism and function of the limbic system, a key brain region for emotion experience, but the underlying molecular mechanism remains unknown. Using whole-brain microvasculature dynamics imaging, the anterior cingulate cortex (ACC) is identified as a key brain region of limbic system involve in the onset of salicylate-induced tinnitus in mice. In the tinnitus group, there is enhanced purine metabolism, oxidative phosphorylation, and a distinct pattern of phosphorylation in glutamatergic synaptic pathway according to the metabolome profiles, quantitative proteomic, and phosphoproteomic data of mice ACC tissue. Electroencephalogram in tinnitus patients with normal hearing thresholds show that the functional connectivity between pregenual anterior cingulate cortex and the primary auditory cortex is significantly increased for high-gamma frequency band, which is positively correlated with the serum glutamate level. These findings indicate that ACC plays an important role in the pathophysiology of tinnitus by interacting with the primary auditory cortex and provide potential molecular targets in the ACC for tinnitus treatment.

Mouse intestinal microbiome modulation by oral administration of a GABA-producing Bifidobacterium adolescentis strain.

The gut microbiome-brain communication signaling has emerged in recent years as a novel target for intervention with the potential to ameliorate some conditions associated with the central nervous system. Hence, probiotics with capacity to produce neurotransmitters, for instance, have come up as appealing alternatives to treat disorders associated with disbalanced neurotransmitters. Herein, we further deep into the effects of administering a gamma-aminobutyric acid (GABA)-producing Bifidobacterium strain, previously demonstrated to contribute to reduce serum glutamate levels, in the gut microbiome composition and metabolic activity in a mouse model. Our results demonstrate that the GABA-producing strain administration results in a specific pattern of gut microbiota modulation, different from the one observed in animals receiving non-GABA-producing strains. This opens new avenues to delineate the specific mechanisms by which IPLA60004 administration contributes to reducing serum glutamate levels and to ascertain whether this effect could exert health benefits in patients of diseases associated with high-glutamate serum concentrations.

Glutamate as a new path in discrimination between neuromyelitis optica spectrum disorder and multiple sclerosis

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) used to be considered as a variant of multiple sclerosis (MS), however the recent detection of a highly specific serum biomarkers for NMOSD have made clear that NMOSD is a condition distinct from MS. The aim was to explore the role of serum glutamate level in the discrimination between NMOSD and relapsing remitting (RR) MS patients during and in between relapses. The study comprised two groups; first group, a total of 30 NMOSD patients, they were furtherly subdivided into NMOSD in remission, 15 patients without recent relapses in the last 3 months, NMOSD with relapse, 15 patients with recent relapses in the last 3 months, the second group, 30 definite, RRMS patients, they were further subdivided into RRMS in remission, 15 patients without recent relapses in the last 3 months RRMS with relapse, 15 patients with recent relapses in the last 3 months.ResultsWithout relapse, NMOSD patients have higher level of serum glutamate than RRMS patients with (P values = 0.005), a significant difference between EDSS in NMOSD patients and RRMS patients (P = 0.0001), The cut-off value of glutamate serum level between NMOSD in remission and RRMS in remission was > 10.3 μg/mL, yet its level for differentiation between group RRMS in remission and RRMS with relapse was > 12.6 μg/mL.ConclusionGlutamate cut-off value might be a reliable tool to discriminate between NMOSD and RRMS.

A Novel Metabolic Score for Predicting the Acute Exacerbation in Patients with Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) has higher mortality when developing to acute exacerbation (AECOPD); hence, the early intervention of COPD is critical for preventing AECOPD. Exploring the serum metabolites associated with acute exacerbation in patients with COPD will contribute to the early intervention of COPD. In the study, a non-targeted metabolomics strategy combined with multivariate statistical methods was performed to explore the metabolic profiling of COPD developing acute exacerbation, to screen the potential metabolites associated with AECOPD and to analyze the potential value of these metabolites in predicting the development of COPD. Serum lysine, glutamine, 3-hydroxybutyrate, pyruvate and glutamate levels were significantly higher, while 1-methylhistidine, isoleucine, choline, valine, alanine, histidine and leucine levels were significantly lower in AECOPD patients, compared with stable COPD patients after normalization based on the healthy controls. Moreover, eight metabolic pathways were significantly altered (P<0.05) in the serum of AECOPD patients compared with the stable COPD population, including purine metabolism, glutamine and glutamate metabolism, arginine biosynthesis, butyrate metabolism, ketone body synthesis and degradation, and linoleic acid metabolism. In addition, the correlation analysis between metabolites and AECOPD patients demonstrated that an M-score based on a weighted sum of concentrations of four metabolites including pyruvate, isoleucine, 1-methylhistidine and glutamine were significantly associated with the acute exacerbation of pulmonary ventilation function in COPD patients. Altogether, the metabolite score based on a weighted sum of concentrations of four serum metabolites was associated with an increased risk of COPD developing acute exacerbation, which will provide a new insight for the understanding of COPD development.

Substantially elevated serum glutamate and CSF GOT-1 levels associated with cerebral ischemia and poor neurological outcomes in subarachnoid hemorrhage patients

Brain injury and cerebral vasospasm during the 14 days after the subarachnoid hemorrhage (SAH) are considered the leading causes of poor outcomes. The primary injury induces a cascade of events, including increased intracranial pressure, cerebral vasospasm and ischemia, glutamate excitotoxicity, and neuronal cell death. The objective of this study was to monitor the time course of glutamate, and associated enzymes, such as glutamate–oxaloacetate transaminase (GOT1), glutamate-pyruvate transaminase (GPT) in cerebrospinal fluid (CSF) and serum, shortly after SAH, and to assess their prognostic value. A total of 74 participants participated in this study: 45 participants with SAH and 29 controls. Serum and CSF were sampled up to 14 days after SAH. SAH participants' clinical and neurological status were assessed at hospitalization, at discharge from the hospital, and 3 months after SAH. Furthermore, a logistic regression analysis was carried out to evaluate the ability of GOT1 and glutamate levels to predict neurological outcomes. Our results demonstrated consistently elevated serum and CSF glutamate levels after SAH. Furthermore, serum glutamate level was significantly higher in patients with cerebral ischemia and poor neurological outcome. CSF GOT1 was significantly higher in patients with uncontrolled intracranial hypertension and cerebral ischemia post-SAH, and independently predicted poor neurological outcomes.

Glutaminase 1 isoform up-regulation associated with lipid metabolism disorder induced by methyl tertiary-butyl ether in male rats

Methyl tertiary-butyl ether (MTBE) is a new unleaded gasoline additive, which is considered to be associated with abnormal lipid metabolism in many studies, but the metabolic characteristics and mechanism are still unclear. To observe the characteristics of lipid metabolism induced by MTBE and possible pathways, 21 male Wistar rats got intragastric administration for 24 weeks. The serum lipid metabolism indexes and metabolites were analyzed separately by a biochemical analyzer and untargeted metabolomics. And found that serum high-density lipoprotein cholesterol (HDL-C) levels in the exposure group were significantly reduced, and serum very low-density lipoprotein (VLDL) levels were significantly increased. In untargeted metabolomics, 190 differential metabolites were obtained. Among them, 23 metabolites were found to show the same trend in MTBE exposure groups, which might play a key role in systemic energy metabolism. Further metabolic pathways analysis showed that D-Glutamine, D-glutamate metabolism, and the other three pathways were affected by MTBE significantly. Therefore, we evaluated serum glutamine and glutamate levels and found that MTBE exposure significantly reduced glutamine levels and increased glutamate levels in rat serum and L-02 cells. Further, the key regulatory gene of glutamine metabolism, glutaminase 1 isoform (GLS1), was significantly up-regulated in rat liver and L-02 cells exposed to MTBE. While the effect of glutamine and glutamate metabolism induced by MTBE could be weakened by BPTES, an antagonist of GLS1. In conclusion, our results indicated that MTBE exposure could change the level of glutamine metabolism by promoting GLS1 expression and ultimately lead to abnormal lipid metabolism.

Antioxidant effects of the aqueous extract of turmeric against hydrogen peroxide-induced oxidative stress in spotted seabass (Lateolabrax maculatus)

Intensive aquaculture-induced oxidative stress is detrimental to fish health and yield. Medicinal plants show promise as natural health boosters and antioxidants in the aquaculture industry. Therefore, this work investigated the effects of turmeric aqueous extract (TAE) on the growth performance, antioxidant status, and hydrogen peroxide (H2O2)-induced oxidative stress in spotted seabass (Lateolabrax maculatus). Fish were fed diets supplemented with 0 (Con), 2 (TAE2), or 4 (TAE4) g/kg TAE for eight weeks, then were injected with H2O2. The results showed that dietary supplementation of TAE did not affect fish growth, feed utilization, or body composition. TAE treatment increased liver antioxidant enzyme activities and decreased liver malondialdehyde content and serum levels of glutamate oxalate transaminase, glutamate pyruvate transaminase, and lactate dehydrogenase. Furthermore, the increases in mortality, liver malondialdehyde content, and serum biomarkers of liver injury in the H2O2-treated fish were inhibited as a consequence of the TAE treatment. In addition, TAE treatment activated the Nrf2/Keap1 pathway in the liver, supported by the up-regulated expression of nrf2, ho-1, and gclc, and down-regulated keap1 expression. Overall, dietary incorporation of TAE protected against H2O2-induced oxidative stress in spotted seabass probably by enhancing antioxidant capacity through the Nrf2/Keap1 pathway.

P14.03.B Glutamate excitotoxicity in brain metastases from lung, breast, and melanoma treated with stereotactic radiosurgery

Abstract Background Brain metastases (BM) are the most frequent neoplasm in the central nervous system (CNS) and primary tumors frequently involved are melanoma, lung cancer and breast cancer. CNS localisation is associated with poor prognosis, and stereotactic radiosurgery (SRS) represents a treatment option for patients with a good performance status. Glutamate (Glu) is a neurotransmitter which plays a facilitating role in carcinogenesis and progression of malignant tumors, as well as in excitotoxicity. Glu efflux from the brain is regulated by scavengers glutamic oxaloacetic transaminase (GOT), glutamate-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH), with aspartate and lactate as catabolites. Glu efflux from the brain seems to be impaired in advanced-stage cancers, resulting in increased blood Glu levels where scavengers exert a protective role. Our hypothesis is that serum Glu and scavengers’ levels are related to neuroinvasion and treatment response in patients with BM and may represent potential biomarkers for BM course and prognosis. Material and Methods Serum Glu scavengers (GOT1, GPT and LDH), serum Glu, aspartate and lactate levels are collected in included patients treated and grouped in A) BM group of patients affected by BM from lung or breast cancer or melanoma, treated with SRS; B) Control-1 group of patients affected by lung cancer, breast cancer or melanoma but without BM and C) Control-2 group of patients with benign intracranial lesions (meningiomas, acoustic schwannomas) treated with SRS.In A) and C) serum metabolites and scavengers will be analyzed before and after SRS treatment (at 3, 6, 9 months) while in B) analyzed once. Blood levels in A) and C) help in identifying differences related to malignancy, the role of SRS and the association with disease control, while blood levels in A) and B) help in detecting differences related to BMs. Exclusion criteria are surgical or previous radiosurgical treatment for BM. This study has received Institutional Ethical Committee approval on 3rd August 2020 (Project NCH04-2020, Clinicaltrials.gov identifier: NCT04785521). Preliminary results Comparison between BM group (n = 32) and Control-1 (n=18) revealed a significant difference in LDH (271.93 vs 217.56 U/L; p 0.041) and lactate (1.86 vs 1.34 mmol/L, p = 0.022) and a trend towards significance in glutamate (103.43 vs 73.74 µmol/L, p = 0.07). Comparison between BM group (n=32) and Control-2 (n = 37) revealed a difference in LDH (271.93 vs 210.89 U/L; p &amp;lt; 0.001), lactate (1.86 vs 1.24 mmol/L; p &amp;lt; 0.001), aspartate (16.36 vs 10.22 µmol/L, p 0.006) and glutamate levels (123 vs 103 µmol/L, p = 0.052). Conclusion The present study is the first one addressing serum glutamate and scavenger levels in patients with BM. If the hypothesis will be confirmed, new targets in glutamate signalling pathway could be identified to define new therapeutic strategies in this challenging disease.

Exercise Regulates the Metabolic Homeostasis of Methamphetamine Dependence.

Physical exercise is effective in enhancing cognitive function, reducing anxiety and depressive symptoms, reducing cravings, and improving quality of life in methamphetamine (METH) addiction. However, little is known about the effect of exercise on metabolic profiles. We performed LC/MS-based targeted metabolic profiling on serum samples to investigate the metabolic characteristics of METH dependence and find the differences between METH-dependent individuals and nonusers and evaluated the metabolomic profiles of individuals with METH dependence following aerobic exercise training. We identified a total of 201 metabolites, among which 115 were differentially expressed under METH use. Among the differentially regulated metabolites, 72 were selected as potential biomarkers. Further analysis identified 19 pathways, among which glyoxylate and dicarboxylate metabolism; alanine, aspartate, and glutamate metabolism; and citrate cycle were most significantly affected by METH. The aerobic exercise intervention differentially regulated 55 metabolites, of which 51 were selected as potential biomarkers and were mainly enriched in 10 pathways. Interestingly, alanine, aspartate, and glutamate metabolism and nitrogen metabolism were the remarkably affected pathways. Furthermore, METH increased the serum levels of glutamate and decreased GABA, whereas exercise decreased the serum levels of glutamate and increased GABA. Results suggested that METH dependency disturbed normal metabolic homeostasis, whereas exercise restored metabolism.

Glutamate Supplementation Improves Growth Performance, Rumen Fermentation, and Serum Metabolites in Heat-Stressed Hu Sheep.

This study evaluated the effect of glutamate supplementation on the physiological parameters of heat-stressed Hu sheep. Forty-eight male Hu sheep with an average initial body weight of 17.74 ± 0.17 kg were randomly divided into two groups: The control group (CON) was fed a basal diet and a treatment group (GLU) was fed a basal diet + 3 g/head/day of L-glutamate. There were six replications in each group with four sheep in each replication for a 90 days feeding test. Growth performance, serum biochemistry, and serum hormones were measured during phase 1 (1–30 days), phase 2 (31–60 days), and phase 3 (61–90 days) of the experiment; rumen fermentation characteristics, nutrient digestibility, and slaughter performance were measured at the end of the experimental periods. There were no differences in growth performance, serum biochemical indices, and immune indices between CON and GLU during phases 1 and 2. However, a higher average daily gain (ADG), a lower average daily feed intake (ADFI), and a lower F:G ratio (ADFI/ADG) were observed in GLU during phase 3 (p < 0.05). Serum levels of glutamate, globulin, immunoglobulin A, immunoglobulin G, immunoglobulin M, and growth hormone in GLU were higher than those in CON only on day 90 (p < 0.05). Serum levels of heat shock protein 70, adrenocorticotrophic hormone, corticosterone, triiodothyronine, and tetraiodothyronine in GLU were lower than those in CON on day 90 (p < 0.05). At the end of the experiment, ruminal pH, microbial crude protein, ammonia nitrogen, and isovalerate concentrations in GLU were higher than those in CON (p < 0.05). The apparent digestibility of dry matter, organic matter, and crude protein in GLU was higher than those in CON (p < 0.05). There were no differences in carcass traits and organ indices but spleen weight and spleen index tended to be higher in GLU. In conclusion, dietary glutamate supplementation improved rumen fermentation, increased nutrition digestibility and metabolism, enhanced immunity, and promoted growth performance of heat-stressed Hu sheep. This suggests that a longer period of glutamate supplementation (not less than 60 days) at a level of 3 g/head/day is beneficial to Hu sheep under heat stress.

The Effects of Enriched Rehabilitation on Cognitive Function and Serum Glutamate Levels Post-stroke.

AimThis study aimed to explore the effect of enriched rehabilitation (ER) on cognitive function and serum glutamate levels in patients with stroke.MethodsForty patients diagnosed with post-stroke cognitive impairment (PSCI), according to the inclusion criteria, and undergoing inpatient rehabilitation were enrolled in the study. Patients were randomly assigned to receive 8 weeks of ER treatment (ER group; n = 20) or conventional medical treatment (CM group; n = 20). In addition, 20 age-matched healthy subjects who were outpatients in our hospital during the same period formed the healthy control (HC) group. In- and between-group differences in cognitive function were assessed during pre-intervention and post-intervention based on the Montreal Cognitive Assessment (MoCA), the Symbol Digit Modalities Test (SDMT), and the Trail Making Test (TMT). The serum levels of glutamate, tumor necrosis factor (TNF), and malondialdehyde (MDA) levels were also detected pre-intervention and post-intervention.ResultsPre-intervention cognitive function and the levels of all the serum parameters assessed significant difference between the HC group and the PSCI group (both ER and CM groups) (p < 0.05), but not between the two groups of patients with PSCI (p > 0.05). Significant improvements were observed in cognitive function in both the ER and the CM groups post-intervention compared with pre-intervention, as evidenced by the measured improvement in MoCA, SDMT, and TMT scores. Similar improvements were seen for serum glutamate, the degree of oxidative damage, and the level of inflammation in both the treatment groups (p < 0.05). More enhancements in cognitive function, including MoCA, SDMT, TMT scores, and the serum levels of glutamate, the degree of oxidative damage, and the level of inflammation were shown in the ER group compared with the CM group post-intervention (p < 0.05).ConclusionsER can improve cognitive function in patients with PSCI. The associated mechanism may be related to the negative regulatory effect of ER on serum glutamate, TNF, and MDA levels, which is likely to enhance synaptic plasticity and alleviate oxidative stress- and inflammation-related damage, at least to some extent.

Effects of glutamate and aspartate on prostate cancer and breast cancer: a Mendelian randomization study

BackgroundRespectively, prostate cancer (PCa) and breast cancer (BC) are the second most and most commonly diagnosed cancer in men and women, and they account for a majority of cancer-related deaths world-wide. Cancer cells typically exhibit much-facilitated growth that necessitates upregulated glycolysis and augmented amino acid metabolism, that of glutamine and aspartate in particular, which is tightly coupled with an increased flux of the tricarboxylic acid (TCA) cycle. Epidemiological studies have exploited metabolomics to explore the etiology and found potentially effective biomarkers for early detection or progression of prostate and breast cancers. However, large randomized controlled trials (RCTs) to establish causal associations between amino acid metabolism and prostate and breast cancers have not been reported.ObjectiveUtilizing two-sample Mendelian randomization (MR), we aimed to estimate how genetically predicted glutamate and aspartate levels could impact upon prostate and breast cancers development.MethodsSingle nucleotide polymorphisms (SNPs) as instrumental variables (IVs), associated with the serum levels of glutamate and aspartate were extracted from the publicly available genome-wide association studies (GWASs), which were conducted to associate genetic variations with blood metabolite levels using comprehensive metabolite profiling in 1,960 adults; and the glutamate and aspartate we have chosen were two of 644 metabolites. The summary statistics for the largest and latest GWAS datasets for prostate cancer (61,106 controls and 79,148 cases) were from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium, and datasets for breast cancer (113,789 controls and 133,384 cases) were from Breast Cancer Association Consortium (BCAC). The study was performed through two-sample MR method.ResultsCausal estimates were expressed as odds ratios (OR) and 95% confidence interval (CI) per standard deviation increment in serum level of aspartate or glutamate. Aspartate was positively associated with prostate cancer (Effect = 1.043; 95% confidence interval, 1.003 to 1.084; P = 0.034) and breast cancer (Effect = 1.033; 95% confidence interval, 1.004 to 1.063; P = 0.028); however, glutamate was neither associated with prostate cancer nor with breast cancer. The potential causal associations were robust to the sensitivity analysis.ConclusionsOur study found that the level of serum aspartate could serve as a risk factor that contributed to the development of prostate and breast cancers. Efforts on a detailed description of the underlying biochemical mechanisms would be extremely valuable in early assessment and/or diagnosis, and strategizing clinical intervention, of both cancers.

Relationship between sleep problems and chronotypes of children and adolescents with attention deficit and hyperactivity disorder and serum GABA, glutamate and homocysteine levels

ABSTRACT In this study, we aimed to determine the relationship between chronotype, sleep problems and serum levels of GABA (gamma amminobutyric acid), glutamate and homocysteine in children and adolescents diagnosed with attention deficit and hyperactivity disorder (ADHD) as well as factors affecting this relationship. Sleep problems of 46 children and adolescents aged 7–18 years diagnosed with ADHD and 30 healthy volunteers aged 7–18 years were evaluated with Children’s Sleep Habits Questionnaire (CSHQ) while chronotypes were evaluated with Children’s Chronotype Questionnaire (CCQ). Serum glutamate, GABA and homocysteine levels were measured using immunosorbent test (ELISA) kits. Sleep problems were significantly more common in the ADHD group compared to the control group (p < .001). Serum GABA, glutamate and homocysteine levels were found to be predictor biomarkers for ADHD, independent of total sleep problem score. When the homocysteine levels were above the cut-off point of 9.445 µmol/L, the sensitivity in early diagnosis of ADHD was 84.8% and the specificity was 70.0%. Although ADHD is a disorder in which sleep problems are common, increased serum GABA, glutamate and homocysteine are important in diagnosing ADHD independent of ADHD-related sleep problems. Homocysteine levels may be an important predictor for the presence of ADHD.

Клініко-неврологічні особливості та вміст нейроамінокислот у хворих із фармакорезистентними лицьовими симпаталгіями

Нами було обстежено 56 хворих із фармакорезистентними лицьовими симпаталгіями різного ступеня вираженості больового синдрому, в сироватці крові яких спектрофотометричним методом визначено базовий вміст глутамату, аспартату та гамма-аміномасляної кислоти для вивчення їх впливу на формування і вираженість больового синдрому. В даній роботі показано, що у хворих із фармакорезистентними лицьовими симпаталгіями з найбільш вираженим больовим синдромом відзначається найбільш значущі зміни вмісту нейроамінокислот, а саме зростання рівня глутамату, зменшення рівня гальмівних амінокислот, зокрема гамма-аміномасляної кислоти, при порівнянні з контролем, що свідчить про неефективність гальмівних механізмів у даної категорії пацієнтів. Необхідним є подальше вивчення особливостей нейроамінокислотного дисбалансу у хворих із фармакорезистентними лицьовими симпаталгіями для розробки диференціально-діагностичних і прогностичних критеріїв перебігу та нових шляхів лікування.

MRNA level of N-methyl-D-aspartic acid receptor NR1 subunit in patients with major depressive disorder and its relationship with clinical features

Objective: To investigate the characteristics of glutamatergic neurotransmitter and neurotransmission dysfunction in patients with major depressive disorder (MDD) and its relationship with clinical characteristics. Methods: Fifty-two patients with MDD and 51 healthy controls were selected. Hamilton Depression scale-17 (HAMD-17) and Hamilton Anxiety Scale (HAMA) were used to evaluate the symptoms of depression and anxiety. The serum glutamate level was measured by enzyme-linked immunosorbent assay (ELISA). Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the mRNA level of NR1 subunit of NMDA receptor. Results: There was no significant difference in gender and age between MDD group and healthy control group. Compared with the control group, the level of serum glutamate [(35±6) mg/L vs (29±6) mg/L, P = 0.021] and mRNA level of NR1 (1.5±0.8 vs 0.8±0.6, P = 0.001) in MDD group were significantly higher. In MDD group, serum glutamate level was positively correlated with depression core symptom score (r = 0.52, P = 0.028), and mRNA level of NR1 subunit was positively correlated with the total course of disease (r = 0.42, P = 0.024). Conclusion: MDD patients may have disorder of glutamatergic neurotransmitter and abnormal expression of NR1 subunit.

Neuropsychiatric Manifestations of Wilson Disease: Correlation with MRI and Glutamate Excitotoxicity.

This study aims to identify neuropsychiatric manifestations in neurological Wilson disease (NWD), and their correlation with MRI changes and glutamate excitotoxicity. Forty-three consecutive patients with NWD from a tertiary care teaching hospital were evaluated prospectively who fulfilled the inclusion criteria. The neuropsychiatric evaluation was done using Neuropsychiatric Inventory (NPI) battery that assesses 12 domains including delusion, hallucination, agitation/aggression, dysphoria/depression, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor activity, appetite change, and abnormal nighttime behavior. Cranial MRI was done using a 3T machine, and locations of signal changes were noted including the total number of MRI lesions. Serum glutamate level was measured by a fluorescence microplate reader. Abnormal NPI in various domains and total NPI scores were correlated with MRI lesions, serum and urinary copper, and glutamate level. The median age of the patients was 16years. Forty-one (48.8%) patients had cognitive impairment and 37 (86%) had movement disorder. Neurobehavioral abnormality was detected in all-commonest being agitation (90.7%) followed by appetite change (81.4%), elation (74.4%), irritability (69.8%), anxiety (67.4%), depression (65.1%), apathy (44.2%), nighttime abnormal behavior (32.6%), aberrant motor behavior (20.9%), delusions (16.3%), and hallucination (18.6%). The thalamic lesion was associated with depression, globus pallidus with depression and anxiety, caudate with anxiety and agitation, brainstem with irritability, and frontal cortex with apathy. Serum glutamate level was higher in NWD. NPI sum score correlated with MRI load and glutamate level. Varying severity of neurobehavioral abnormalities are common in the patients with NWD and correlate with the location of MRI lesion and glutamate level.