Postharvest melatonin treatment enhanced antioxidant activity and promoted GABA biosynthesis in yellow-flesh peach.

The effects of postharvest melatonin treatment on antioxidant activity and γ-aminobutyric acid (GABA) biosynthesis in yellow-flesh peach fruit stored at 4 °C and 90% RH for 28 d were explored. Results showed that melatonin treatment was effective in maintaining firmness, total soluble solids content and color in peach fruit. Melatonin treatment significantly reduced H2O2 and MDA contents, enhanced high level of non-enzymatic antioxidant system (ABTS∙+ scavenging capacity), and increased the activity or content of antioxidant enzymes including CAT, POD, SOD and APX. Melatonin treatment increased the contents of total soluble protein and glutamate, while reducing total free amino acid content. Moreover, melatonin treatment up-regulated the expression of GABA biosynthesis genes (PpGAD1 and PpGAD4) and suppressed the expression of GABA degradation gene (PpGABA-T), resulting in the accumulation of endogenous GABA. These findings indicated that melatonin treatment exerted positive effects on improving antioxidant activity and promoting GABA biosynthesis in yellow-flesh peach fruit.

Changes in gamma-aminobutyric acid and glutamate/glutamine levels in the right thalamus of patients with episodic and chronic migraine: A proton magnetic resonance spectroscopy study.

OBJECTIVE: To explore gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels in the right thalamus of patients with episodic migraine (EM) and chronic migraine (CM) and their effects on the chronification of migraine. BACKGROUND: Migraine affects approximately 1 billion people worldwide, with 2.5%-3% of people with EM progressing to CM each year. Magnetic resonance spectroscopy studies have revealed altered GABA and Glx levels in the thalamus of patients with migraine without aura, but these neurometabolic concentrations are underexplored in the thalamus of patients with CM. METHODS: In this cross-sectional study, patients with EM and CM were recruited. Mescher-Garwood point resolved spectroscopy sequence was used to acquire neurotransmitter concentrations in the right thalamus of patients with EM and CM and matched healthy controls (HCs). RESULTS: A total of 26 patients (EM, n = 11; CM, n = 15) and 16 age- and sex-matched HCs were included in the analysis. There were significantly lower GABA+/Water levels in the right thalamus of the CM group (mean ± standard deviation: 2.27 ± 0.4 [institutional units]) than that of the HC group (2.74 ± 0.4) (p = 0.026; mean difference [MD] = -0.5 [i.u.]), and lower Glx/Cr levels in the EM group (mean ± SD: 0.11 ± < 0.1) than in the HCs (0.13 ± < 0.1) and CM group (0.13 ± < 0.1) (p = 0.023, MD < -0.1, and p = 0.034, MD < -0.1, respectively). The GABA+/Glx ratio was lower in the CM group (mean ± SD: 0.38 ± 0.1) compared to the EM group (0.47 ± 0.1) (p = 0.024; MD = -0.1). The area under the curve for GABA+/Water levels in differentiating patients with CM from HCs was 0.83 (95% confidence interval 0.68, 0.98; p = 0.004). Correlation analyses within the migraine group revealed no significant correlation between metabolite concentration levels and headache characteristics after Bonferroni correction. CONCLUSION: Reduced GABA+/Water levels and imbalance of excitation/inhibition in the right thalamus may contribute to migraine chronification.

Ultrasound accelerated γ-aminobutyric acid accumulation in coffee leaves through influencing the microstructure, enzyme activity, and metabolites.

Gamma-aminobutyric acid (GABA) is a non-protein amino acid that possesses various physiological functions. Our previous study has shown that ultrasound increased GABA accumulation in coffee leaves. In this study, we aimed to uncover the GABA enrichment mechanism by investigating the surface microstructure, cellular permeability, enzyme activities, and metabolomics of coffee leaves under ultrasound treatment. The results showed that ultrasound increased the electrical conductivity and the activities of glutamate decarboxylase, γ-aminoaldehyde dehydrogenase, and diamine oxidase by 12.0%, 265.9%, 124.1%, 46.8%, respectively. Environmental scanning electron microscope analysis demonstrated an increased opening of stomata and the rougher surface in the leaves after ultrasound treatment. UPLC-qTOF-MS/MS-based untargeted metabolomics analysis identified 82 differential metabolites involved in various metabolism pathways. Our results indicated that ultrasound changed the surface microstructure of coffee leaves, thereby accelerating the migration of glutamate into the cells; activated related enzymes; regulated C/N metabolism pathways, which led to an increase of GABA.

Comprehensive profiling of bioactive compounds in germinated black soybeans via UHPLC-ESI-QTOF-MS/MS and their anti-Alzheimer's activity.

Black soybeans contain several bioactive compounds and commonly consumed due to their health-related activities but rarely cultivated as edible sprouts. The present study investigated the changes that occurred during germination in two new genotypes black soybeans. Raw and germinated seeds were tested against in vitro Alzheimer's disease (AD) biomarkers, including oxidative stress, inflammatory factors and cholinesterase enzymes as well as γ-aminobutyric acid (GABA) levels. Sprouts significantly inhibited the cholinesterase enzymes and inflammatory factors (protein denaturation, proteinase and lipoxygenase) than seeds. An increase in phenolic, flavonoid and GABA (10-folds) content and antioxidant capacity (ABTS, DPPH, and FRAP) was observed in germinated seeds. However, anthocyanin content was decreased in sprouts. UHPLC-ESI-QTOF-MS2 metabolites profiling approach identified 22 compounds including amino acids, peptides, fatty acids, and polyphenols. Among identified compounds, daidzein, genistein, gallic acid, spermidine, L-asparagine, and L-lysine exhibited the highest increase after germination. The current study reveals that germination of black soybeans have promising potential to inhibit/prevent AD and can be used to develop functional foods.

Effect of DRD4 Receptor -616 C/G Polymorphism on Thalamic GABA Levels in Pediatric Patients With Primary Nocturnal Enuresis.

BACKGROUND: The single nucleotide polymorphism (SNP) of dopamine D4 receptor (DRD4) promoter (-616; rs747302) is associated with abnormalities of the thalamus in children suffering from primary nocturnal enuresis (PNE). PURPOSE: To investigate the effect of DRD4 -616 C/G SNP on thalamic gamma-aminobutyric acid (GABA) levels in PNE children. STUDY TYPE: Prospective, observational. SUBJECTS: One hundred and seventy-six children with PNE and 161 healthy control children. FIELD STRENGTH/SEQUENCE: 3 T, three-dimensional T1-weighted turbo field echo sequence and MEscher-Garwood Point RESolved Spectroscopy (MEGA-PRESS) MRS sequence. ASSESSMENT: The MEGA-PRESS MRS sequence was used to measure thalamic GABA spectra. The thalamic GABA+ level was calculated using the Gannet 3.0 software package for each participant. A questionnaire was used to determine arousal from sleep (AS) scores. STATISTICAL TESTS: Comparisons of the AS scores and thalamic GABA+ levels were performed using the Mann-Whitney U test between C-allele carriers and GG homozygotes in the PNE and control groups. Spearman correlation analysis was performed to determine the association between AS scores and thalamic GABA levels in PNE children. RESULTS: Thalamic GABA levels in the PNE group were significantly higher than those in the healthy control group (0.178 (0.169-0.186) vs. 0.154 (0.146-0.164), Z = 8.526, Pcorrected < 0.001). The GABA levels in C-allele carriers were significantly higher than those in GG homozygotes in both the PNE and control groups (0.184 (0.181-0.193) vs. 0.170 (0.165-0.177), Z = 8.683, Pcorrected < 0.001; 0.166 (0.156-0.170) vs. 0.147 (0.141-0.152), Z = 9.445, Pcorrected < 0.001). GABA levels in the thalamus were also significantly and positively correlated with AS scores in C-allele carriers in the PNE group (r = 0.747, P < 0.05). DATA CONCLUSION: DRD4 -616 C allele may be associated with increased thalamic GABA+ levels, especially in C-allele carrying PNE children. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

Neurobehavioral effects of acute low-dose whole-body irradiation.

Radiation exposure has multiple effects on the brain, behavior and cognitive functions. It has been reported that high-dose (>20 Gy) radiation-induced behavior and cognitive aberration partly associated with severe tissue destruction. Low-dose (<3 Gy) exposure can occur in radiological disasters and cerebral endovascular treatment. However, only a few reports analyzed behavior and cognitive functions after low-dose irradiation. This study was undertaken to assess the relationship between brain neurochemistry and behavioral disruption in irradiated mice. The irradiated mice (0.5 Gy, 1 Gy and 3 Gy) were tested for alteration in their normal behavior over 10 days. A serotonin (5-HT), Dopamine, gamma-Aminobutyric acid (GABA) and cortisol analysis was carried out in blood, hippocampus, amygdala and whole brain tissue. There was a significant decline in the exploratory activity of mice exposed to 3 Gy and 1 Gy radiation in an open field test. We observed a significant short-term memory loss in 3 Gy and 1 Gy irradiated mice in Y-Maze. Mice exposed to 1 Gy and 3 Gy radiation exhibited increased anxiety in an elevated plus maze (EPM). The increased anxiety and memory loss patterns were also seen in 0.5 Gy irradiated mice, but the results were not statistically significant. In this study we observed that neurotransmitters are significantly altered after irradiation, but the neuronal cells in the hippocampus were not significantly affected. This study suggests that the low-dose radiation-induced cognitive impairment may be associated with the neurochemical in low-dose irradiation and unlike the high-dose scenario might not be directly related to the morphological changes in the brain.

Effect of Different Drying Methods on the Nutritional Value of Hibiscus sabdariffa Calyces as Revealed by NMR Metabolomics.

Red mature calyces of Hibiscus sabdariffa were collected from 16 different locations in Meghalaya, India. Samples were processed using shade drying (SD) and tray drying (TD). NMR spectroscopy was used to assess the metabolic composition of the calyces. In this study, 18 polar metabolites were assigned using 1D and 2D NMR spectra, and 10 of them were quantified. Proximate analysis showed that the TD method is more efficient at reducing moisture and maintaining the ash content of the Hibiscus biomass. NMR metabolomics indicates that the metabolite composition significantly differs between SD and TD samples and is more stable in TD plant processing. The differences in post-harvest drying has a greater impact on the metabolite composition of Hibiscus than the plant location.

Whole-brain R1 predicts manganese exposure and biological effects in welders.

Manganese (Mn) is a neurotoxicant that, due to its paramagnetic property, also functions as a magnetic resonance imaging (MRI) T1 contrast agent. Previous studies in Mn toxicity have shown that Mn accumulates in the brain, which may lead to parkinsonian symptoms. In this article, we trained support vector machines (SVM) using whole-brain R1 (R1 = 1/T1) maps from 57 welders and 32 controls to classify subjects based on their air Mn concentration ([Mn]Air), Mn brain accumulation (ExMnBrain), gross motor dysfunction (UPDRS), thalamic GABA concentration (GABAThal), and total years welding. R1 was highly predictive of [Mn]Air above a threshold of 0.20 mg/m3 with an accuracy of 88.8% and recall of 88.9%. R1 was also predictive of subjects with GABAThal having less than or equal to 2.6 mM with an accuracy of 82% and recall of 78.9%. Finally, we used an SVM to predict age as a method of verifying that the results could be attributed to Mn exposure. We found that R1 was predictive of age below 48 years of age with accuracies ranging between 75 and 82% with recall between 94.7% and 76.9% but was not predictive above 48 years of age. Together, this suggests that lower levels of exposure (< 0.20 mg/m3 and < 18 years of welding on the job) do not produce discernable signatures, whereas higher air exposures and subjects with more total years welding produce signatures in the brain that are readily identifiable using SVM.

Baseline measures of cerebral glutamate and GABA levels in individuals at ultrahigh risk for psychosis: Implications for clinical outcome after 12 months.

BACKGROUND: Cerebral glutamate and gamma-aminobutyric acid (GABA) levels might predict clinical outcome in individuals at ultrahigh risk (UHR) for psychosis but have previously primarily been investigated in smaller cohorts. We aimed to study whether baseline levels of glutamate and GABA in anterior cingulate cortex (ACC) and glutamate in thalamus could predict remission status and whether baseline metabolites differed in the remission versus the nonremission group. We also investigated the relationship between baseline metabolite levels and severity of clinical symptoms, functional outcome, and cognitive deficits at follow-up. METHODS: About 124 UHR individuals were recruited at baseline. In this, 74 UHR individuals were clinically and cognitively assessed after 12 months, while remission status was available for 81 (25 remission/56 nonremission). Glutamate and GABA levels were assessed at baseline using 3 T proton magnetic resonance spectroscopy. Psychopathology, symptom severity, and remission were assessed with the Comprehensive Assessment of At-Risk Mental States and Clinical Global Impression and functional outcome with the Social and Occupational Functioning Assessment Scale. Cognitive function was estimated with the Cambridge Neuropsychological Test Automated Battery. RESULTS: There were no differences between baseline glutamate and GABA levels in subjects in the nonremission group compared with the remission group, and baseline metabolites could not predict remission status. However, higher baseline levels of GABA in ACC were associated with clinical global improvement (r = -0.34, N = 51, p = 0.01) in an explorative analysis. CONCLUSIONS: The variety in findings across studies suggests a probable multifactorial influence on clinical outcome in UHR individuals. Future studies should combine multimodal approaches to attempt prediction of long-term outcome.

Nutritional composition and bioactivity of germinated Thai indigenous rice extracts: A feasibility study.

The feasibility of the production of germinated rice extracts using indigenous rice from Southern Thailand, including Khemtong (KHT) and Khai Mod Rin (KMR) from a single location at the Pak Phanang River Basin in Nakhon Si Thammarat, was investigated. The nutritional composition and bioactivity of the germinated rice extracts from both cultivars were evaluated. Optimum germination time for both rices was 96 h, leading to the highest GABA, thiamine, free amino acid, total sugar, and α-amylase activity (p<0.05). Germinated KHT had a higher α-amylase activity than germinated KMR at all germination times. Mashing at 60°C/pH 5.5 rendered the extract with the highest GABA content (p<0.05) and desirable contents of other nutrients. In comparison with germinated Sungyod (local colored rice) and Jasmine (commercial Thai rice) extracts, KHT and KMR showed a higher scavenging activity against DPPH•, OH•, and H2O2 (p<0.05) with a comparable ABTS•+ inhibition. For metal chelation, reducing power and ACE inhibitory activity, the germinated Sungyod extract was greater than KHT/KMR. The results demonstrated the potential use of germinated local Thai rice for the production of functional beverages.

Free L-glutamate-induced modulation in oxidative and neurochemical profile contributes to enhancement in locomotor and memory performance in male rats.

Glutamate (Glu), the key excitatory neurotransmitter in the central nervous system, is considered essential for brain functioning and has a vital role in learning and memory formation. Earlier it was considered as a harmful agent but later found to be useful for many body functions. However, studies regarding the effects of free L-Glu administration on CNS function are limited. Therefore, current experiment is aimed to monitor the neurobiological effects of free L-Glu in male rats. L-Glu was orally administered to rats for 5-weeks and changes in behavioral performance were monitored. Thereafter, brain and hippocampus were collected for oxidative and neurochemical analysis. Results showed that chronic supplementation of free L-Glu enhanced locomotor performance and cognitive function of animals which may be attributed to the improved antioxidant status and cholinergic, monoaminergic and glutamatergic neurotransmission in brain and hippocampus. Current results showed that chronic supplementation of L-Glu affects the animal behaviour and brain functioning via improving the neurochemical and redox system of brain. Free L-Glu could be a useful therapeutic agent to combat neurological disturbances however this requires further targeted studies.

Genetic and metabolic links between the murine microbiome and memory.

BACKGROUND: Recent evidence has linked the gut microbiome to host behavior via the gut-brain axis [1-3]; however, the underlying mechanisms remain unexplored. Here, we determined the links between host genetics, the gut microbiome and memory using the genetically defined Collaborative Cross (CC) mouse cohort, complemented with microbiome and metabolomic analyses in conventional and germ-free (GF) mice. RESULTS: A genome-wide association analysis (GWAS) identified 715 of 76,080 single-nucleotide polymorphisms (SNPs) that were significantly associated with short-term memory using the passive avoidance model. The identified SNPs were enriched in genes known to be involved in learning and memory functions. By 16S rRNA gene sequencing of the gut microbial community in the same CC cohort, we identified specific microorganisms that were significantly correlated with longer latencies in our retention test, including a positive correlation with Lactobacillus. Inoculation of GF mice with individual species of Lactobacillus (L. reuteri F275, L. plantarum BDGP2 or L. brevis BDGP6) resulted in significantly improved memory compared to uninoculated or E. coli DH10B inoculated controls. Untargeted metabolomics analysis revealed significantly higher levels of several metabolites, including lactate, in the stools of Lactobacillus-colonized mice, when compared to GF control mice. Moreover, we demonstrate that dietary lactate treatment alone boosted memory in conventional mice. Mechanistically, we show that both inoculation with Lactobacillus or lactate treatment significantly increased the levels of the neurotransmitter, gamma-aminobutyric acid (GABA), in the hippocampus of the mice. CONCLUSION: Together, this study provides new evidence for a link between Lactobacillus and memory and our results open possible new avenues for treating memory impairment disorders using specific gut microbial inoculants and/or metabolites. Video Abstract.

Thalamic Gamma Aminobutyric Acid Level Changes in Major Depressive Disorder After a 12-Week Iyengar Yoga and Coherent Breathing Intervention.

Objective: To determine if a 12-week yoga intervention (YI) was associated with increased gamma aminobutyric acid (GABA) levels and decreased depressive symptoms in participants with major depressive disorder (MDD). Methods: Subjects were randomized to a high-dose group (HDG) of three YIs a week and a low-dose group (LDG) of two YIs a week. Thalamic GABA levels were obtained using magnetic resonance spectroscopy at Scan-1 before randomization. After the assigned 12-week intervention, Scan-2 was obtained, immediately followed by a YI and Scan-3. Beck Depression Inventory II (BDI-II) scores were obtained before Scan-1 and Scan-3. Settings/Location: Screenings and interventions occurred at the Boston University Medical Center. Imaging occurred at McLean Hospital. Subjects: Subjects met criteria for MDD. Intervention: Ninety minutes of Iyengar yoga and coherent breathing at five breaths per minute plus homework. Outcome measures: GABA levels and the BDI-II. Results: BDI-II scores improved significantly in both groups. GABA levels from Scan-1 to Scan-3 and from Scan-2 to Scan-3 were significantly increased in the LDG (n = 15) and showed a trend in the total cohort. Post hoc, participants were divided into two groups based on having an increase in GABA levels at Scan-2. Increases in Scan-2 GABA levels were observed in participants whose mean time between their last YI and Scan-2 was 3.93 ± 2.92 standard deviation (SD) days, but not in those whose mean time between their last YI and Scan-2 was 7.83 ± 6.88 SD. Conclusions: This study tentatively supports the hypothesis that one of the mechanisms through which yoga improves mood is by increasing the activity of the GABA system. The observed increase in GABA levels following a YI that was no longer observed 8 days after a YI suggests that the associated increase in GABA after a YI is time limited such that at least one YI a week may be necessary to maintain the elevated GABA levels.

Towards direct analysis of solid and liquid samples exploiting a 3D printed dialysis unit and sequential injection: Application for automated derivatization and determination of gamma-aminobutyric acid in foodstuff and beverages.

In this work, a new design of a dialysis unit for direct analysis of solid and liquid samples is presented. The homemade unit was constructed using a 3D printer due to its simple and fast fabrication ability. The dialysis unit is composed of cylindrical-shaped donor and acceptor chambers. A stainless steel sieve is installed inside the donor chamber. SEM images clearly showed that the sieve prevented membrane blockage by suspension particles in the sample. Multiple dialysis units were connected to a sequential injection (SI) system for serial determination of gamma-aminobutyric acid (GABA) in solid and liquid samples. The dialysate from each dialysis unit was consecutively aspirated into the SI flow line for on-line derivatization of GABA with 2-hydroxy-1-naphthaldehyde (3.0% w/v). The derivative was detected spectrophotometrically at 425 nm. The linear calibration range extended to 1000 mg L-1 GABA (r2 > 0.99) with high precision (1.2 %RSD). The developed system was applied to analysis of dietary supplements, grains of germinated brown rice and milk. The samples were directly introduced into the donor chamber either as powder or liquids. The measured GABA content using the developed method was compared using high performance liquid chromatography, with good agreement using Pearson's correlation (r2 = 0.9999). The method has high accuracy based on recovery studies (99.8 ± 1.5%) and high sample throughput (64 samples h-1).

Treatment response after 6 and 26 weeks is related to baseline glutamate and GABA levels in antipsychotic-naïve patients with psychosis.

BACKGROUND: Poor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and γ-aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs). METHODS: Thirty-nine antipsychotic-naïve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response. RESULTS: Before treatment, thalamic glutamate/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate/Cr and GABA/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA/Cr in ACC. Baseline levels in responders and HCs did not differ. CONCLUSION: Glutamatergic and GABAergic abnormalities in antipsychotic-naïve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients.

Anxiolytic and memory enhancing potential of aloe vera and flax seed oil in rats: A comparative study with valproic acid.

For centuries, herbs and herbal oils are used for pharmacological purpose. Aloe vera is well-known as silent healer and flax seed oil is known to contain rich amount of omega-3 fatty acids, both are having effects on central nervous system. Valproic acid is anticonvulsant drug with some side effects and has shown effects on behaviors. This study was designed to monitor the effects of valproic acid, aloe vera and flax seed oil on cognitive and anxiolytic behaviors in rats. Animals were categorized into four groups: Control, valproic acid, aloe vera and flax seed oil which were respectively treated with water, valproic acid (300mg/kg), aloe vera (0.4ml/kg) and flax seed oil (1.8ml/kg). The treatment was continued 2 weeks for drug and 3 weeks for aloe vera and flax seed oil. Anxiolytic effect as well as increased GABA levels were observed following drug and oil treatments. Improvement in cognitive function with decrease in acetylcholine esterase activity in aloe vera and flax seed oil while impairment in learning memory with increase acetylcholine esterase activity was observed in rats treated with valproic acid. Results showed substantial decrease in acetylcholinesterase level in aloe vera and flax seed oil supporting the cognitive impact of oils in contrary to drug.

Rutin, γ-Aminobutyric Acid, Gallic Acid, and Caffeine Negatively Affect the Sweet-Mellow Taste of Congou Black Tea Infusions.

The sweet-mellow taste sensation is a unique and typical feature of premium congou black tea infusions. To explore the key taste-active compounds that influence the sweet-mellow taste, a sensory and molecular characterization was performed on thirty-three congou black tea infusions presenting different taste qualities, including the sweet-mellow, mellow-pure, or less-mellow taste. An integrated application of quantitative analysis of 48 taste-active compounds, taste contribution analysis, and further validation by taste supplementation experiments, combined with human sensory evaluation revealed that caffeine, γ-aminobutyric acid, rutin, succinic acid, citric acid, and gallic acid negatively affect the sweet-mellow taste, whereas glucose, sucrose, and ornithine positively contribute to the sweet-mellow taste of congou black tea infusions. Particularly, rutin, γ-aminobutyric acid, gallic acid, and caffeine, which impart the major inhibitory effect to the manifestation of the sweet-mellow taste, were identified as the key influencing components through stepwise screening and validation experiments. A modest level of these compounds was found to be favorable for the development and manifestation of the sweet-mellow taste. These compounds might potentially serve as the regulatory targets for oriented-manufacturing of high-quality sweet-mellow congou black tea.

Short echo-time Magnetic Resonance Spectroscopy in ALS, simultaneous quantification of glutamate and GABA at 3 T.

Cortical hyperexcitability has been found in early Amyotrophic Lateral Sclerosis (ALS) and is hypothesized to be a key factor in pathogenesis. The current pilot study aimed to investigate cortical inhibitory/excitatory balance in ALS using short-echo Magnetic Resonance Spectroscopy (MRS). Patients suffering from ALS were scanned on a 3 T Trio Siemens MR scanner using Spin Echo Full Intensity Acquired Localized (SPECIAL) Magnetic Resonance Spectroscopy in primary motor cortex and the occipital lobe. Data was compared to a group of healthy subjects. Nine patients completed the scan. MRS data was of an excellent quality allowing for quantification of a range of metabolites of interest in ALS. In motor cortex, patients had Glutamate/GABA and GABA/Cr- ratios comparable to healthy subjects. However, Glutamate/Cr (p = 0.002) and the neuronal marker N-acetyl-aspartate (NAA/Cr) (p = 0.034) were low, possibly due to grey-matter atrophy, whereas Glutathione/Cr (p = 0.04) was elevated. In patients, NAA levels correlated significantly with both hand strength (p = 0.027) and disease severity (p = 0.016). In summary SPECIAL MRS at 3 T allows of reliable quantification of a range of metabolites of interest in ALS, including both excitatory and inhibitory neurotransmitters. The method is a promising new technique as a biomarker for future studies on ALS pathophysiology and monitoring of disease progression.

Strength of resting state functional connectivity and local GABA concentrations predict oral reading of real and pseudo-words.

Reading is a learned activity that engages multiple cognitive systems. In a cohort of typical and struggling adult readers we show evidence that successful oral reading of real words is related to gamma-amino-butyric acid (GABA) concentration in the higher-order language system, whereas reading of unfamiliar pseudo-words is not related to GABA in this system. We also demonstrate the capability of resting state functional connectivity (rsFC) combined with GABA measures to predict single real word compared to pseudo-word reading performance. Results show that the strength of rsFC between left fusiform gyrus (L-FG) and higher-order language systems predicts oral reading behavior of real words, irrespective of the local concentration of GABA. On the other hand, pseudo-words, which require grapheme-to-phoneme conversion, are not predicted by the connection between L-FG and higher-order language system. This suggests that L-FG may have a multi-functional role: lexical processing of real words and grapheme-to-phoneme processing of pseudo-words. Additionally, rsFC between L-FG, pre-motor, and putamen areas are positively related to the oral reading of both real and pseudo-words, suggesting that text may be converted into a phoneme sequence for speech initiation and production regardless of whether the stimulus is a real word or pseudo-word. In summary, from a systems neuroscience perspective, we show that: (i) strong rsFC between higher order visual, language, and pre-motor areas can predict and differentiate efficient oral reading of real and pseudo-words. (ii) GABA measures, along with rsFC, help to further differentiate the neural pathways for previously learned real words versus unfamiliar pseudo-words.

Neurochemical effects of motor cortex stimulation in the periaqueductal gray during neuropathic pain.

OBJECTIVE: Motor cortex stimulation (MCS) is a neurosurgical technique used to treat patients with refractory neuropathic pain syndromes. MCS activates the periaqueductal gray (PAG) matter, which is one of the major centers of the descending pain inhibitory system. However, the neurochemical mechanisms in the PAG that underlie the analgesic effect of MCS have not yet been described. The main goal of this study was to investigate the neurochemical mechanisms involved in the analgesic effect induced by MCS in neuropathic pain. Specifically, we investigated the release of γ-aminobutyric acid (GABA), glycine, and glutamate in the PAG and performed pharmacological antagonism experiments to validate of our findings. METHODS: Male Wistar rats with surgically induced chronic constriction of the sciatic nerve, along with sham-operated rats and naive rats, were implanted with both unilateral transdural electrodes in the motor cortex and a microdialysis guide cannula in the PAG and subjected to MCS. The MCS was delivered in single 15-minute sessions. Neurotransmitter release was evaluated in the PAG before, during, and after MCS. Quantification of the neurotransmitters GABA, glycine, and glutamate was performed using a high-performance liquid chromatography system. The mechanical nociceptive threshold was evaluated initially, on the 14th day following the surgery, and during the MCS. In another group of neuropathic rats, once the analgesic effect after MCS was confirmed by the mechanical nociceptive test, rats were microinjected with saline or a glycine antagonist (strychnine), a GABA antagonist (bicuculline), or a combination of glycine and GABA antagonists (strychnine+bicuculline) and reevaluated for the mechanical nociceptive threshold during MCS. RESULTS: MCS reversed the hyperalgesia induced by peripheral neuropathy in the rats with chronic sciatic nerve constriction and induced a significant increase in the glycine and GABA levels in the PAG in comparison with the naive and sham-treated rats. The glutamate levels remained stable under all conditions. The antagonism of glycine, GABA, and the combination of glycine and GABA reversed the MCS-induced analgesia. CONCLUSIONS: These results suggest that the neurotransmitters glycine and GABA released in the PAG may be involved in the analgesia induced by cortical stimulation in animals with neuropathic pain. Further investigation of the mechanisms involved in MCS-induced analgesia may contribute to clinical improvements for the treatment of persistent neuropathic pain syndromes.