GABA Concentrations Research Articles

GABA and Glutamate in hMT+ Link to Individual Differences in Residual Visual Function After Occipital Stroke.

Damage to the primary visual cortex following an occipital stroke causes loss of conscious vision in the contralateral hemifield. Yet, some patients retain the ability to detect moving visual stimuli within their blind field. The present study asked whether such individual differences in blind field perception following loss of primary visual cortex could be explained by the concentration of neurotransmitters γ-aminobutyric acid (GABA) and glutamate or activity of the visual motion processing, human middle temporal complex (hMT+). We used magnetic resonance imaging in 19 patients with chronic occipital stroke to measure the concentration of neurotransmitters GABA and glutamate (proton magnetic resonance spectroscopy) and functional activity in hMT+ (functional magnetic resonance imaging). We also tested each participant on a 2-interval forced choice detection task using high-contrast, moving Gabor patches. We then measured and assessed the strength of relationships between participants' residual vision in their blind field and in vivo neurotransmitter concentrations, as well as visually evoked functional magnetic resonance imaging activity in their hMT+. Levels of GABA and glutamate were also measured in a sensorimotor region, which served as a control. Magnetic resonance spectroscopy-derived GABA and glutamate concentrations in hMT+ (but not sensorimotor cortex) strongly predicted blind-field visual detection abilities. Performance was inversely related to levels of both inhibitory and excitatory neurotransmitters in hMT+ but, surprisingly, did not correlate with visually evoked blood oxygenation level-dependent signal change in this motion-sensitive region. Levels of GABA and glutamate in hMT+ appear to provide superior information about motion detection capabilities inside perimetrically defined blind fields compared to blood oxygenation level-dependent signal changes-in essence, serving as biomarkers for the quality of residual visual processing in the blind-field. Whether they also reflect a potential for successful rehabilitation of visual function remains to be determined.

How anaerobic treatment is controlling the volatile components and key odorants of purple-colored leaf tea

Special purple-colored leaf tea products rich in γ-aminobutyric acid (GABA) have recently gained popularity. Although anaerobic treatment could effectively increase the GABA content in tea products, it also imparted an unknown unpleasant aroma. This study aimed to elucidate the dynamic effects of anaerobic treatment on volatile components during the purple-colored leaf tea processing and reveal the key aroma-active components. A total of 112 volatile components were identified, and it was found that anaerobic treatment could facilitate the accumulation of 2-heptanol, (E)− 2-hexenal, ethyl salicylate, phenylethyl alcohol, and (E,E)− 2,4-decadienal, but inhibited the formation of (Z)− 3-hexenyl acetate and methyl jasmonate. Moreover, 17 potent odorants including (E)-β-ionone, linalool, hexanal, 2-heptanol, (Z)− 3-nonen-1-ol, and (E,E)− 2,4-decadienal were distinguished as the key odorants of purple-colored leaf tea products rich in GABA based on gas chromatography–olfactometry and odor activity value analysis. These results provide new insights into the effect of anaerobic treatment on tea volatile metabolites.

Effects of Seed Germination on Physicochemical and Bioactive Compounds Characteristics of Velvet Bean Tempe

Indonesia, known as the largest tempe-producing country globally with approximately 160,000 producers, faces a challenge in meeting the demand for tempe due to insufficient local soybean supply. To address this issue, Indonesia has been compelled to import significant quantities of soybeans, reaching 1.68 million tons in 2020, which escalated by 47.78% to 2.49 million tons in 2021. This study aims to scientifically investigate the impact of velvet bean seed germination on the physicochemical characteristics and bioactive components of velvet bean tempe. The research methodology involved quantitative analysis to obtain reliable results. The preliminary analysis established that the optimal velvet bean tempe fermentation time was 48 hours. Following germination, the physical properties of velvet bean sprouts exhibited an increase in weight accompanied by a reduction in bulk density and absolute density. Furthermore, the germination treatment resulted in decreased brightness, saturation, whiteness, and pH values, while simultaneously increasing the hardness of the tempe. Chemical analysis demonstrated that germination of velvet bean seeds led to an elevation in moisture content and a decrease in carbohydrate content within the produced tempe. Additionally, bioactive component analysis revealed that the germination treatment contributed to a reduction in total phenol content from 52.46 to 36.30 mg AAE/100g, antioxidant capacity from 132.80 to 66.90 mg GAE/100g, and GABA content from 54.20 to 21.50 mg/100g in the tempe. These findings provide valuable scientific insights into alternative ingredient utilisation and production processes optimisation of velvet bean tempe.

Investigation on the Quality of Commercially Available GABA Tea in Taiwan

This study collected 220 commercially available samples of γ-Aminobutyric acid (GABA) tea produced in Taiwan from 2016 to 2021. The 220 tea samples were categorized into five types of GABA tea, including 108 GABA Oolong tea, 71 GABA Black tea, 21 GABA Paochong tea, 12 GABA Green tea, and 8 GABA Puerh tea samples. The most common type of GABA tea in Taiwan is GABA Oolong tea, followed by GABA Black tea. The physico-chemical constituents and consumer acceptance of the GABA tea samples were analyzed. The GABA content varied among the different types of GABA tea: GABA Oolong tea ranged from 128–286 mg/100 g, GABA Black tea ranged from 182–360 mg/100 g, GABA Paochong tea ranged from 98–203 mg/100 g, GABA Green tea ranged from 56–174 mg/100 g, and GABA Puerh tea ranged from 142–191 mg/100 g. In terms of the commercial standard of GABA tea, 22 out of the 220 GABA tea samples failed to meet the commercial standard, with a failure rate of 10%. During the fermentation process of GABA tea, the contents of GABA increased significantly, but the total polyphenol and total catechin contents remained stable. In terms of consumer acceptance, GABA Black tea is the most accepted by consumers, followed by GABA Puerh tea, GABA Paochong, and GABA Oolong tea. The sour flavor in GABA tea is similar to the original sour sensory properties found in black tea. It is assumed that this is the main reason GABA Black tea has the highest acceptance.

Development of a workflow for the selection, identification and optimization of lactic acid bacteria with high γ-aminobutyric acid production

Lactic acid bacteria produce γ-aminobutyric acid (GABA) as an acid stress response. GABA is a neurotransmitter that may improve sleep and resilience to mental stress. This study focused on the selection, identification and optimization of a bacterial strain with high GABA production, for development as a probiotic supplement. The scientific literature and an industry database were searched for probiotics and potential GABA producers. In silico screening was conducted to identify genes involved in GABA production. Subsequently, 17 candidates were screened for in vitro GABA production using thin layer chromatography, which identified three candidate probiotic strains Levilactobacillus brevis DSM 20054, Lactococcus lactis DS75843and Bifidobacterium adolescentis DSM 24849 as producing GABA. Two biosensors capable of detecting GABA were developed: 1. a transcription factor-based biosensor characterized by the interaction with the transcriptional regulator GabR was developed in Corynebacterium glutamicum; and 2. a growth factor-based biosensor was built in Escherichia coli, which used auxotrophic complementation by expressing 4-aminobutyrate transaminase (GABA-T) that transfers the GABA amino group to pyruvate, hereby forming alanine. Consequently, the feasibility of developing a workflow based on co-culture with producer strains and a biosensor was tested. The three GABA producers were identified and the biosensors were encapsulated in nanoliter reactors (NLRs) as alginate beads in defined gut-like conditions. The E. coli growth factor-based biosensor was able to detect changes in GABA concentrations in liquid culture and under gut-like conditions. L. brevis and L. lactis were successfully encapsulated in the NLRs and showed growth under miniaturized intestinal conditions.

Antiepileptics pharmacotherapy or antidiabetics may hold potential in ‎treatment of ‎‎epileptic ‎patients with diabetes mellitus: A narrative review

Several studies have reported the association of diabetes mellitus with epilepsy. With respect to ‎the management of diabetes–epilepsy patients, these studies pointed out the beneficial effects of ‎the ketogenic diet. Ketogenic diets may have antiepileptic properties as the utilization of ketone ‎bodies in the brain instead of glucose delays or inhibits the degradation of γ-aminobutyric acid ‎‎(GABA) transaminase, and thereby enhances the concentration of GABA. By restoring normal ‎intracerebral GABA levels and reducing the cerebral inflammation linked to epilepsy, metformin ‎is useful in preventing seizures. Sitagliptin is one of the dipeptidyl dipeptidase-4 inhibitors, ‎which have a positive impact on epilepsy in experimental animal models with pentylenetetrazole-‎induced seizures, by reducing reactive oxygen species, (antioxidant effect), normalization of ‎GABA level, suppression of neuroinflammation (autophagy) and reduced neuronal damage ‎‎(antiapoptotic effect). Weight gain is a well-known side effect of anti-seizure medications. ‎Sodium valproate can cause dyslipidemia and inhibit glucose transporter-1 in the brain, putting ‎patients with epilepsy and diabetes at risk of developing atherosclerosis. It's worth looking at ‎how ferroptosis and autophagy contribute to the etiology of diabetes and epilepsy, as well as ‎how antiepileptics and antidiabetics alter these pathological processes. Therefore, it was worth ‎performing a narrative-review on the effects of antiepileptics on diabetes, the effect of ‎antidiabetics on epilepsy, as well the net results of antiepileptic–antidiabetic interactions in those ‎patients.‎

Cenobamate and Clobazam Combination as Personalized Medicine in Autoimmune-Associated Epilepsy With Anti-Gad65 Antibodies.

Autoimmune-associated epilepsy (AAE) with antiglutamic acid decarboxylase 65 (GAD65) antibodies is considered a T-cell-mediated encephalitis that evolves to drug-resistant epilepsy. We do not have an effective therapeutic strategy for these patients. Because the GAD enzyme is primarily responsible for the conversion of glutamate to GABA, the mechanism of epileptogenesis in this condition predicts decreased levels of GABA content in synaptic vesicles. Cenobamate (CNB) acts as a positive allosteric modulator at synaptic and extra synaptic GABAA receptors, producing increased inhibitory neurotransmission in the brain. This mechanism could be especially beneficial in AAE with anti-GAD65 antibodies because it would be able to correct the imbalance due to the GABAergic stimulation deficit in postsynaptic neurons. We recruit a retrospective multicentric consecutive case series of AAE with anti-GAD65 antibodies from 5 epilepsy units in Spain who have received treatment with CNB. A total of 8 patients were recruited. This cohort of highly refractory patients have failed a mean of 9.50 (SD = 3.20) ASM without control of seizures for sustained periods of time. The average number of seizures per month during the previous 3 months before CNB treatment was 19.63 (SD = 17.03). After the introduction of CNB improvement was achieved in all our patients, with a median reduction in the number of seizures of 92.22% (interquartile range [IQR]: 57.25-98.75). The mean follow-up was 156.75 days (SD = 68.23). In patients with concomitant treatment with clobazam (CLB), the median percentage of seizure reduction was higher than those not taking CLB: 94.72% (IQR: 87.25-100) vs 41.50% (p = 0.044) and also higher than the control group of patients with refractory epilepsy not related to anti-GAD65 treated with the same combination: 94.72% (IQR: 87.25-100) vs 45.00% (IQR: 25.00-87.00) (p = 0.019). Treatment with the combination CNB + CLB could be a type of personalized medicine in patients with AAE with anti-GAD65. Our preliminary data will need to be endorsed with new prospective and controlled studies.

GABAB Receptors Tonically Inhibit Motoneurons and Neurotransmitter Release from Descending and Primary Afferent Fibers.

Motoneurons receive thousands of excitatory and inhibitory synapses from descending tracts and primary afferent fibers. The excitability of these neurons must be precisely regulated to respond adequately to the requirements of the environment. In this context, GABAA and GABAB receptors regulate motoneuron synaptic strength. GABAA and GABAB receptors are expressed on primary afferent fibers and motoneurons, while in the descending afferent fibers, only the GABAB receptors are expressed. However, it remains to be known where the GABA that activates them comes from since the GABAergic interneurons that make axo-axonic contacts with primary afferents have yet to be identified in the descending afferent terminals. Thus, the main aim of the present report was to investigate how GABAB receptors functionally modulate synaptic strength between Ia afferent fibers, excitatory and inhibitory descending fibers of the dorsolateral funiculus, and spinal motoneurons. Using intracellular recordings from the spinal cord of the turtle, we provide evidence that the GABAB receptor antagonist, CGP55845, not only prevents baclofen-induced depression of EPSPs but also increases motoneuron excitability and enhances the synaptic strength between the afferent fibers and motoneurons. The last action of CGP55845 was similar in excitatory and inhibitory descending afferents. Interestingly, the action of baclofen was more intense in the Ia primary afferents than in the descending afferents. Even more, CGP55845 reversed the EPSP depression induced by the increased concentration of ambient GABA produced by interneuron activation and GABA transporter blockade. Immunofluorescence data corroborated the expression of GABAB receptors in the turtle's spinal cord. These findings suggest that GABAB receptors are extrasynaptic and tonically activated on descending afferent fibers and motoneurons by GABA released from astrocytes and GABAergic interneurons in the cellular microenvironment. Finally, our results also suggest that the antispastic action of baclofen may be due to reduced synaptic strength between descending fibers and motoneurons.

Cortical excitability in human somatosensory and visual cortex: implications for plasticity and learning - a minireview.

The balance of excitation and inhibition plays a key role in plasticity and learning. A frequently used, reliable approach to assess intracortical inhibition relies on measuring paired-pulse behavior. Moreover, recent developments of magnetic resonance spectroscopy allows measuring GABA and glutamate concentrations. We give an overview about approaches employed to obtain information about excitatory states in human participants and discuss their putative relation. We summarize paired-pulse techniques and basic findings characterizing paired-pulse suppression in somatosensory (SI) and (VI) visual areas. Paired-pulse suppression describes the effect of paired sensory stimulation at short interstimulus intervals where the cortical response to the second stimulus is significantly suppressed. Simultaneous assessments of paired-pulse suppression in SI and VI indicated that cortical excitability is not a global phenomenon, but instead reflects the properties of local sensory processing. We review studies using non-invasive brain stimulation and perceptual learning experiments that assessed both perceptual changes and accompanying changes of cortical excitability in parallel. Independent of the nature of the excitation/inhibition marker used these data imply a close relationship between altered excitability and altered performance. These results suggest a framework where increased or decreased excitability is linked with improved or impaired perceptual performance. Recent findings have expanded the potential role of cortical excitability by demonstrating that inhibition markers such as GABA concentrations, paired-pulse suppression or alpha power predict to a substantial degree subsequent perceptual learning outcome. This opens the door for a targeted intervention where subsequent plasticity and learning processes are enhanced by altering prior baseline states of excitability.

Metagenomics-based inference of microbial metabolism towards neuroactive amino acids and the response to antibiotics in piglet colon.

Gut-derived neuroactive metabolites from amino acids perform a broad range of physiological roles in the body. However, the interaction between microbiota and epithelium in the metabolism of amino acids with neuroactive properties remains unclear in the colon of piglets. To investigate the microbial and epithelial metabolism, metagenomics and mucosal metabolomics were performed using colonic samples from 12 ileum-canulated piglets subjected to a 25-day infusion with saline or antibiotics. We categorized 23 metabolites derived from the metabolism of tryptophan, glutamate, and tyrosine, known as precursors of neuroactive metabolites. Microbial enzymes involved in the kynurenine synthesis via arylformamidase, 4-aminobutyric acid (GABA) synthesis via putrescine aminotransferase, and tyramine synthesis via tyrosine decarboxylase were identified in Clostridiales bacterium, uncultured Blautia sp., and Methanobrevibacter wolinii, respectively. Antibiotics significantly affected the microbiota involved in tryptophan-kynurenine and glutamate-GABA metabolism. An increase in the relative abundance of putrescine aminotransferase and Blautia sp. correlated positively with an increase in luminal GABA concentration. Overall, our findings provide new insights into the microbial ability to metabolize key amino acids that are precursors of neuroactive metabolites.

Integrating animal experiments, mass spectrometry and network-based approach to reveal the sleep-improving effects of Ziziphi Spinosae Semen and γ-aminobutyric acid mixture

BackgroundZiziphi Spinosae Semen (ZSS) is a plant widely used as medicine and food in Asian countries due to its numerous health benefits. γ-aminobutyric acid (GABA), a non-proteinaceous amino acid, is one of the major inhibitory neurotransmitters with a relaxant function. In this study, a system pharmacology approach was employed to assess the effects of a mixture composed of ZSS and GABA (ZSSG) on sleep improvement.MethodsMice were divided into five groups (n = 10) and received either no treatment, sodium pentobarbital, or sodium barbital with diazepam or ZSSG. The effects of ZSSG on sleep quality were evaluated in mice, and differential metabolites associated with sleep were identified among the control, ZSS, GABA, and ZSSG groups. Additionally, network-based ingredient-insomnia proximity analysis was applied to explore the major ingredients.ResultsZSSG significantly improved sleep quality by decreasing sleep latency and prolonging sleep duration in sodium pentobarbital-induced sleeping mouse model (P < 0.05). ZSSG significantly enhanced the brain content of GABA in mice. Furthermore, ZSSG also significantly decreased sleep latency-induced by sodium barbital in mice (P < 0.05). Metabolic analysis revealed significant differences in 10 metabolites between ZSSG group and the groups administering ZSS or GABA. Lastly, using the network-based ingredient screening model, we discovered potential four active ingredients and three pairwise ingredient combinations with synergistic effect on insomnia from ZSSG among 85 ingredients identified by UPLC-Q/TOF–MS. Also, we have constructed an online computation platform.ConclusionOur data demonstrated that ZSSG improved the sleeping quality of mice and helped to balance metabolic disorders-associated with sleep disorders. Moreover, based on the network-based prediction method, the four potential active ingredients in ZSSG could serve as quality markers-associated with insomnia. The network-based framework may open up a new avenue for the discovery of active ingredients of herbal medicine for treating complex chronic diseases or symptoms, such as insomnia.

Sex-related exacerbation of injury-induced mechanical hypersensitivity in GAD67 haplodeficient mice.

Decreased GABA levels in injury-induced loss of spinal inhibition are still under intense interest and debate. Here, we show that GAD67 haplodeficient mice exhibited a prolonged injury-induced mechanical hypersensitivity in postoperative, inflammatory, and neuropathic pain models. In line with this, we found that loss of 1 copy of the GAD67-encoding gene Gad1 causes a significant decrease in GABA contents in spinal GABAergic neuronal profiles. Consequently, GAD67 haplodeficient males and females were unresponsive to the analgesic effect of diazepam. Remarkably, all these phenotypes were more pronounced in GAD67 haplodeficient females. These mice had significantly much lower amount of spinal GABA content, exhibited an exacerbated pain phenotype during the second phase of the formalin test, developed a longer lasting mechanical hypersensitivity in the chronic constriction injury of the sciatic nerve model, and were unresponsive to the pain relief effect of the GABA-transaminase inhibitor phenylethylidenehydrazine. Our study provides strong evidence for a role of GABA levels in the modulation of injury-induced mechanical pain and suggests a potential role of the GABAergic system in the prevalence of some painful diseases among females.

Annotation of genes involved in gamma-aminobutyric multiplication during coix germination by metabolome and transcriptome analysis

ABSTRACT Job’s tears (coix) is a widely used grain with rich and balanced nutritional value. In this study, a total of 71 metabolites, including amino acid metabolism, sugar metabolism and fatty acid metabolism, were significantly increased in the germinating coix through liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Significant increase in gamma-aminobutyric (GABA) content during seed germination was detected in the metabolites detected. Transcript profiles generated through high-throughput RNA-sequencing data and 2431 differentially expressed genes (DEGs) were identified. The functional of DEGs were also significantly clustered in glucose metabolism and fatty acid metabolism. In the annotation of metabolite variation and differentially expressed genes, 23 regulatory genes and 10 significantly enriched metabolites for GABA content proliferation during coix germination were identified by association analysis. These results provided a theoretical basis for understanding the germination mechanism of coix and promoting its production and application.

Effect of Noise and Music on Neurotransmitters in the Amygdala: The Role Auditory Stimuli Play in Emotion Regulation.

Stress caused by noise is becoming widespread globally. Noise may lead to deafness, endocrine disorders, neurological diseases, and a decline in mental health. The mechanism behind noise-induced neurodevelopmental abnormalities is unclear, but apoptosis and pro-inflammatory signals may play an important role. In this study, weaned piglets were used as a model to explore noise-induced neurodevelopmental abnormalities. We hypothesized that long-term noise exposure would induce anxiety and cause acute stress, exhibited by alterations in neurotransmission in the amygdala. A total of 72 hybrid piglets (Large White × Duroc × Min Pig) were randomly divided into three groups, including noise (exposed to mechanical noise, 80-85 dB), control (blank, exposed to natural background sound, <40 dB), and music (positive control, exposed to Mozart K.448, 60-70 dB) groups. The piglets were exposed to 6 h of auditory noise daily (10:00-16:00) for 28 days. Compared with the control group, piglets exposed to noise showed more aggressive behavior. The expression of Caspase3, Caspase9, Bax, NF-κB (p56), TLR4, MYD88, I κ B α, IL-1 β, TNF-α, and IL-12RB2 was significantly upregulated in the amygdala, while the expression of Nrf2, HO-1, CAT, and SOD was downregulated in piglets in the noise group. Cell death occurred, and numerous inflammatory cells accumulated in the amygdala of piglets in the noise group. Targeted metabolomics showed that the content of inhibitory neurotransmitter GABA was higher in the amygdala of piglets in the noise group. Compared with the noise group, piglets in the music group displayed more positive emotion-related behaviors. Compared with the noise group, the expression of genes related to apoptosis, inflammation, and oxidative damage was lower in the music group. Cells of the amygdala in the music group were also of normal morphology. Our results show that noise-induced stress causes apoptosis and neuroinflammation in the amygdala and induces anxiety during the early neonatal neural development of piglets. In contrast, to some extent, music alleviates noise-induced anxiety.

Influences of UV-B treatment and cooking methods on bioactive components in germinated highland barley

This study explored the impacts of UV-B radiation and cooking methods on the content and release of bioactive components in germinated highland barley. Optimal UV-B radiation (0.2 W m−2 for 6 h/d) increased flavonoid content by the third day, whereas excessive radiation (0.4 W m−2) caused a decrease. Under 0.1 W m−2 UV-B radiation for 9 h/d, polyphenol content rose by 34.40%, and under 0.2 W m−2 for 6 h/d, it increased by 49.40%. After three days of germination under 0.2 W m−2 irradiation for 12 h/d, riboflavin content reached up to 2.5 μg/g. GABA content in the control group increased by 40.21% on the third day compared to the initial, with the highest content in samples irradiated for 3 h/d under 0.2 and 0.4 W m−2. β-glucan content in the control group decreased by 20.15% on the third day compared to the initial, with a more pronounced decrease under long-time high radiation. Different cooking methods affected the release of these components during in vitro digestion. Microwaving proved to be the most effective treatment for promoting the release of flavonoids, polyphenols, riboflavin, and β-glucan, but it was less favorable for GABA release. These findings offer insights for optimizing the nutritional quality of germinated highland barley.

Controlled germination of grain crops is an effective way to processing low-quality raw materials

Relevance. The development of technologies of cereal crops germination and obtaining of raw ingredients with increased antioxidant properties, containing in their composition biologically active substances of natural origin, will allow to form a modern domestic market of useful food products to maintain the health of the country in the long term. One such approach could be controlled germination of grain crops by ultrasonic treatment during the soaking stage. This technology will maximise the yield of finished products per unit of processed raw material, process low-quality raw materials and create products with increased nutritional value.Methods. The objects of the study were three samples of grain crops: wheat, barley, oats. At the initial stage, incoming quality control of raw materials and their disinfection by physical method of exposure were carried out. For experimental samples of cereal crops at the stage of soaking the impact of ultrasound (22 ± 1.25 kHz) 245 W/l for 5 min, then the grain was soaked for 8 hours (wheat grain) and 12 hours (barley and oats grain), the process of germination was carried out until reaching the sprout size 1.5–2 mm in more than 90% of grains. All operations with control samples were performed in the same sequence, excluding the process of ultrasound exposure. The total content of flavonoids and polyphenolic compounds was determined in all tested samples using spectrophotometric method, total antioxidant activity using DPPH-method, and γ-aminobutyric acid content using automated liquid chromatography system.Results. The studies showed that all germinated samples of cereal crops are characterized by sufficiently high values of flavonoid and polyphenolic compounds. At the same time, the samples obtained by ultrasound exposure showed an increase in the content of flavonoids by an average of 7.3–8.9 times, polyphenols by 2–5.6 times. In the process of intensified controlled germination, the total antioxidant activity increased by 31.6–40.0%, relative to the control samples of grain crops. The increase in GABA content in samples after ultrasound exposure averaged 360–490%. The results confirmed the possibility and feasibility of using the proposed technology of controlled germination in obtaining raw ingredients from germinated cereal crops. The study was carried out with the financial support of the Russian Science Foundation Grant 23-26-00290.

Contribution of Putrescine and Glutamic Acid on γ-Aminobutyric Acid Accumulation of Malus baccata Borkh. Roots under Suboptimal Low Root-Zone Temperature

GABA (γ-aminobutyric acid) is found in plants and accumulates rapidly under stresses. However, the contributions of glutamic acid and a (Glu)-derived pathway and polyamines (PAs) catabolism pathway on GABA accumulation and the regulatory effects of exogenous putrescine (Put) on a GABA shunt under suboptimal low root-zone temperatures remain unknown. Our results showed that suboptimal low root-zone temperatures (treatment L) significantly increased GABA contents and GABA transaminase (GABA-T) activities. The contribution rate of the PAs catabolism pathway increased from 20.60% to 43.31%. Treatment L induced oxidative stress in Malus baccata Borkh. roots. Exogenous Put increased the contents of endogenous Put, spermine (Spm), and spermidine (Spd), promoted the transformation of PAs, increased the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), and decreased the contents of hydrogen peroxide (H2O2), superoxide anion (O2∙−), and malondialdehyde (MDA). Meanwhile, contrasting results were observed after aminoguanidine (AG, an inhibitor of diamine oxidase) application. These findings revealed that the Glu-derived pathway is the main route of GABA synthesis. The contribution rate of the Pas catabolism pathway increased gradually with the extension of treatment time, and the treatment of exogenous Put significantly improved the tolerance of Malus baccata Borkh. Roots to suboptimal low temperature by regulating the transformation of Pas, GABA shunt, and the antioxidant system.

Effects of γ-aminobutyric acid supplementation on glucose control in adults with prediabetes: A double-blind, randomized, placebo-controlled trial

BackgroundGamma-aminobutyric acid (GABA) is mainly known as an endogenously produced neurotransmitter. However, GABA intake from dietary sources like tomatoes and fermented foods can be considerable. Studies in rodent models have shown beneficial effects of oral GABA supplementation on glucose homeostasis and cardiovascular health. Still, it is currently unknown whether oral GABA supplementation produces cardiometabolic benefits in humans. ObjectivesThis study aimed to investigate whether oral GABA supplementation can improve glucose homeostasis in individuals at risk of developing type 2 diabetes. MethodsIn a randomized, placebo-controlled, double-blind, parallel-arm trial, 52 individuals with prediabetes (classified by impaired glucose tolerance and/or impaired fasting glucose), aged 50 to 70 y with a body mass index ≥25 kg/m2 received either 500 mg GABA 3 times daily or a placebo for 95 days. The primary outcome was the effect of the intervention on glucose response after an OGTT. As exploratory secondary outcomes, markers of glycemic control (glycated hemoglobin, insulin, glucagon, mean amplitude of glycemic excursions, and standard deviation as measured with flash glucose monitoring), cardiovascular health (blood pressure, 24-h blood pressure, circulating triglycerides, cholesterol), and self-reported sleep quality were measured before and after the intervention. ResultsCompared with placebo, GABA supplementation for 95 days did not change the postprandial glucose response (0.21 mmol/L; 95% confidence interval: −0.252, 0.674; P = 0.364). After correction for the false discovery rate, all other outcomes (including fasting plasma GABA concentration) showed no significant effects from GABA intervention at a group level. ConclusionsGABA supplementation does not change the postprandial glucose response in individuals at risk of developing type 2 diabetes. However, based on findings in secondary outcome measures, further research is warranted in other study populations. Research could focus on the effects of GABA in individuals with advanced diabetes or other cardiometabolic disorders.This trial was registered at www.clinicaltrials.gov as NCT04303468.

A comparative approach on the spray and freeze drying of probiotic and Gamma-aminobutyric acid as a single entity: Characterization and evaluation of stability in simulated gastrointestinal conditions

To promote the adequate supplementation of probiotics and bioactives in food formulations, this study aimed to develop synbiotic co-microcapsules containing probiotic strain Lactococcus lactis SKL 13 and bioactive compound, namely γ-Aminobutyric acid (GABA), using spray (at the air inlet and outlet temperatures of 110 ± 2 °C and 50 ± 5 °C, respectively, with a feed flow rate of 2.5 mL min−1) and freeze-drying (at - 40 °C temperature, 1 mbar pressure for 12 h) in a ternary exopolysaccharide (such as maltodextrin, dextran, and inulin in a combination of 8.41, 4.59, and 0.40 g/100 mL, respectively) matrix. The freeze-drying resulted in higher probiotic and GABA encapsulation efficiencies of 95.08 and 90.04%, respectively, than spray drying (probiotics: 93.12% and GABA: 83.46%). The absence of diffraction peaks indicated an amorphous metastable state of microcapsules. Only ∼1% reduction in probiotic count and ∼5% decrease in GABA content were observed in dried capsules after 60 days of storage as well as both the powders showed non-significant (p > 0.05) reduction in probiotic count (2.9 and 1.35 log CFU/mL in intestinal and gastric conditions, respectively) and 80% release of GABA after 240 min of simulated gastrointestinal conditions. The Fourier-transform infrared (FTIR) and scanning electron microscopy (SEM) results further confirmed the proper embedding of probiotics and GABA in the dried microcapsules. The lower moisture content (4.15%), good flowability and higher thermal decomposition peaks at an elevated temperature of 308 °C exhibited by spray-dried powder compared to freeze-dried particles indicated their greater potentiality for high-temperature food applications.

Prebiotics modulate the microbiota-gut-brain axis and ameliorate cognitive impairment in APP/PS1 mice.

Prebiotics, including fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS), stimulate beneficial gut bacteria and may be helpful for patients with Alzheimer's disease (AD). This study aimed to compare the effects of FOS and GOS, alone or in combination, on AD mice and to identify their underlying mechanisms. Six-month-old APP/PS1 mice and wild-type mice were orally administered FOS, GOS, FOS + GOS or water by gavage for 6weeks and then subjected to relative assays, including behavioral tests, biochemical assays and 16S rRNA sequencing. Through behavioral tests, we found that GOS had the best effect on reversing cognitive impairment in APP/PS1 mice, followed by FOS + GOS, while FOS had no effect. Through biochemical techniques, we found that GOS and FOS + GOS had effects on multiple targets, including diminishing Aβ burden and proinflammatory IL-1β and IL-6 levels, and changing the concentrations of neurotransmitters GABA and 5-HT in the brain. In contrast, FOS had only a slight anti-inflammatory effect. Moreover, through 16S rRNA sequencing, we found that prebiotics changed composition of gut microbiota. Notably, GOS increased relative abundance of Lactobacillus, FOS increased that of Bifidobacterium, and FOS + GOS increased that of both. Furthermore, prebiotics downregulated the expression levels of proteins of the TLR4-Myd88-NF-κB pathway in the colons and cortexes, suggesting the involvement of gut-brain mechanism in alleviating neuroinflammation. Among the three prebiotics, GOS was the optimal one to alleviate cognitive impairment in APP/PS1 mice and the mechanism was attributed to its multi-target role in alleviating Aβ pathology and neuroinflammation, changing neurotransmitter concentrations, and modulating gut microbiota.