GABA Concentrations Research Articles

Screening and characterization of lactic acid bacteria and fermentation of gamma-aminobutyric acid-enriched bamboo shoots.

In order to produce fermented bamboo shoots with functional properties, two strains of lactic acid bacteria were selected for inoculation and fermentation. One strain, Lactiplantibacillus plantarum R1, exhibited prominent potential probiotic properties (including gastrointestinal condition tolerance, adhesion ability, antimicrobial ability, and antibiotic resistance), while the other, Levilactobacillus brevis R2, demonstrated the capability of high γ-aminobutyric acid (GABA) production (913.99 ± 14.2 mg/L). The synergistic inoculation of both strains during bamboo shoot fermentation led to a remarkable increase in GABA content (382.31 ± 12.17 mg/kg), surpassing that of naturally fermented bamboo shoots by more than 4.5 times and outperforming mono-inoculated fermentation. Simultaneously, the nitrite content was maintained at a safe level (5.96 ± 1.81 mg/kg). Besides, inoculated fermented bamboo shoots exhibited an increased crude fiber content (16.58 ± 0.04 g/100 g) and reduced fat content (0.39 ± 0.02 g/100 g). Sensory evaluation results indicated a high overall acceptability for the synergistically inoculated fermented bamboo shoots. This study may provide a strategy for the safe and rapid fermentation of bamboo shoots and lay the groundwork for the development of functional vegetable products enriched with GABA.

Exogenous γ-Aminobutyric Acid (GABA) Enhanced Response to Abiotic Stress in Hypsizygus marmoreus by Improving Mycelial Growth and Antioxidant Capacity.

γ-Aminobutyric (GABA) acid is a nutrient and signaling molecule existing in many plants, participating in the regulation of metabolism and various physiological activities. Two strains of Hypsizygus marmoreus (a white variety and a brown variety) were investigated to study the impact of exogenous GABA on mycelial growth and the response to stress. Mycelial growth, microscopic morphology, antioxidant profile, and gad2 expression in H. marmoreu were investigated under salt, dehydration, or cold stress. The results indicated that 5 mM GABA stimulated mycelial growth under standard cultivation conditions, whereas GABA addition over 10 mM hindered the growth. Under salt, dehydration, or cold stress, treatment with 5 mM GABA significantly enhanced the mycelial growth rate and density of both H. marmoreus strains by promoting front hyphae branching. Meanwhile, the activities of key antioxidant enzymes such as peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) were enhanced by GABA, thereby augmenting the defensive network against abiotic stress. Additionally, gad2 expression and GABA concentration were increased under abiotic stresses as a resistance regulation response. The exogenous addition of GABA strengthened the upregulation of gad2 expression and GABA production. These findings indicated that exogenously adding low concentrations of GABA effectively enhanced the mycelial growth and antioxidant profile of H. marmoreus, thereby improving its resistance against stresses.

Predicting and optimizing reactive oxygen species metabolism in Punica granatum L. through machine learning: role of exogenous GABA on antioxidant enzyme activity under drought and salinity stress

BackgroundDrought and salinity stress have been proposed as the main environmental factors threatening food security, as they adversely affect crops' agricultural productivity. As a potential solution, the application of plant growth regulators to enhance drought and salinity tolerance has gained considerable attention. γ-aminobutyric acid (GABA) is a four-carbon non-protein amino acid that accumulates in plants as a response to stressful conditions. This study focused on a comparative assessment of several machine learning (ML) regression models, including radial basis function, generalized regression neural network (GRNN), random forest (RF), and support vector regression (SVR) to develop predictive models for assessing the effect of different concentrations of GABA (0, 10, 20, and 40 mM) on various physio-biochemical traits during periods of drought, salinity, and combined stress conditions. The physio-biochemical traits included antioxidant enzyme activities (superoxide dismutase, SOD; peroxidase, POD; catalase, CAT; and ascorbate peroxidase, APX), protein content, malondialdehyde (MDA) levels, and hydrogen peroxide (H2O2) levels. The non‑dominated sorting genetic algorithm‑II (NSGA‑II) was employed for optimizing the superior prediction model.ResultsThe GRNN model outperformed the other ML algorithms and was therefore selected for optimization by NSGA-II. The GRNN-NSGA-II model revealed that treatment with GABA at concentrations of 20.90 mM and 20.54 mM, under combined drought and salinity stress conditions at 20.86 and 20.72 days post-treatment, respectively, could result in the maximum values for protein content (by 0.80 and 0.69), APX activity (by 50.63 and 51.51), SOD activity (by 0.54 and 0.53), POD activity (by 1.53 and 1.72), CAT activity (by 4.42 and 5.66), as well as lower MDA levels (by 0.12 and 0.15) and H2O2 levels (by 0.44 and 0.55), respectively, in the ‘Atabaki’ and ‘Rabab’ cultivars.ConclusionsThis study demonstrates that the GRNN-NSGA-II model, as an advanced ML algorithm with a strong predictive ability for outcomes in combined stressful environmental conditions, provides valuable insights into the significant factors influencing such multifactorial processes.

Increased stress vulnerability in the offspring of socially isolated rats: Behavioural, neurochemical and redox dysfunctions

Stressful events during pregnancy impact on the progeny neurodevelopment. However, little is known about preconceptional stress effects. The rat social isolation represents an animal model of chronic stress inducing a variety of dysfunctions. Moreover, social deprivation during adolescence interferes with key neurodevelopmental processes. Here, we investigated the development of behavioural, neurochemical and redox alterations in the male offspring of socially isolated female rats before pregnancy, reared in group (GRP) or in social isolation (ISO) from weaning until young-adulthood. To this aim, females were reared in GRP or in ISO conditions, from PND21 to PND70, when they were mated. Their male offspring was housed in GRP or ISO conditions through adolescence and until PND70, when passive avoidance-PA, novel object recognition-NOR and open field-OF tests were performed. Levels of noradrenaline (NA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), glutamate (GLU) and GABA were assessed in the prefrontal cortex (PFC). Moreover, cortical ROS levels were quantified, as well as NF-kB and the NADPH oxidase NOX2 expression, redox status (expressed as GSH:GSSG ratio) and SOD1 amount.A significant decrease of the latency time in the PA was observed in the offspring of ISO females. In the NOR test, while a significant increase in the exploratory activity towards the novel object was observed in the offspring of GRP females, no significant differences were found in the offspring of ISO females. No significant differences were found in the OF test among experimental groups. Theoffspring of ISO females showed increased NA and 5-HIAA levels, whereas in the offspring persistently housed in isolation condition from weaninguntil adulthood, we detected reduced 5-HT levels and ehnanced 5-HIAA amount. No significant changes in GLU concentrations were detected, while decreased GABA content was observed in the offspring of ISO females exposed to social isolation. Increased ROS levels as well as reduced NF-κB, NOX2 expression were detected in the offspring of ISO females. This was accompanied by reduced redox status and enhanced SOD1 levels.In conclusion, our results suggest that female exposure to chronic social stress before pregnancy might have a profound influence on the offspring neurodevelopment in terms of cognitive, neurochemical and redox-related alterations, identifying this specific time window for possible preventive and therapeutic strategies.

Culture-dependent and -independent analyses of bacterial compositions and its contributions to formation of γ-aminobutyric acid and poly-γ-glutamic acid in Cheonggukjang

This study was performed to unveil bacterial compositions and their contributions to the formation of γ-aminobutyric acid (GABA) and poly-γ-glutamic acid (γ-PGA) in Cheonggukjang. To predict possible key factors contributing to the content of the bioactive compounds in Cheonggukjang, commercial products were analyzed for various parameters. The content of GABA and γ-PGA showed a negative (R2 = 0.61 – 0.73) and positive correlation (R2 = 0.53 – 0.96) with antioxidative activity. Consistently, GABA content showed a moderate negative correlation with γ-PGA content (R2 = 0.58). Among the physicochemical and microbial parameters, only salinity showed a moderate negative correlation with γ-PGA content (R2 = 0.75), which might be due to the inhibition of bacterial growth. It was also suggested that multiple factors (including bacterial species) were involved in the formation of GABA and γ-PGA in Cheonggukjang. To reveal dominant bacterial species and further presume their contributions to the bioactive compound formation in Cheonggukjang, both culture-independent (metagenomic) and -dependent (culturomic) methods were used. Culture-independent method showed that Bacillus piscis was dominant (23.37 – 94.89 %), followed by B. hisashii (0.00 – 62.45 %) and B. coagulans (0.00 – 13.82 %). Considering the quantitative speciation data on the bioactive compound content in Cheonggukjang (and bacterial production capability) together, it was further elucidated that B. piscis contributed primarily to the bioactive compound formation. Unlike this, culture-dependent analysis revealed that B. licheniformis and B. subtilis were dominant (30.0 – 47.6 and 17.5 – 39.5 %, respectively). Based on the quantitative speciation data on the bacterial production capability of GABA and γ-PGA, B. subtilis was the primarily contributing bacterial species to the bioactive compound formation. Consequently, it was observed that the bacterial compositions and their contributions to the bioactive compound formation determined by the two methods differed considerably, i.e., B. piscis and B. subtilis were identified to be prominent bacterial contributors, respectively, depending on the method used.

Attenuation of Streptozotocin-Induced Diabetic Neuropathic Allodynia by Flavone Derivative Through Modulation of GABA-ergic Mechanisms and Endogenous Biomarkers.

Diabetic neuropathic pain is one of the most devasting disorders of peripheral nervous system. The loss of GABAergic inhibition is associated with the development of painful diabetic neuropathy. The current study evaluated the potential of 3-Hydroxy-2-methoxy-6-methyl flavone (3-OH-2'MeO6MF), to ameliorate peripheral neuropathic pain using an STZ-induced hyperglycemia rat model. The pain threshold was assessed by tail flick, cold, mechanical allodynia, and formalin test on days 0, 14, 21, and 28 after STZ administration accompanied by evaluation of several biochemical parameters. Administration of 3-OH-2'-MeO6MF (1,10, 30, and 100mg/kg, i.p) significantly enhanced the tail withdrawal threshold in tail-flick and tail cold allodynia tests. 3-OH-2'-MeO6MF also increased the paw withdrawal threshold in mechanical allodynia and decreased paw licking time in the formalin test. Additionally, 3-OH-2'-MeO6MF also attenuated the increase in concentrations of myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), nitrite, TNF-α, and IL 6 along with increases in glutathione (GSH). Pretreatment of pentylenetetrazole (PTZ) (40mg/kg, i.p.) abolished the antinociceptive effect of 3-OH-2'-MeO6MF in mechanical allodynia. Besides, the STZ-induced alterations in the GABA concentration and GABA transaminase activity attenuated by 3-OH-2'-MeO6MF treatment suggest GABAergic mechanisms. Molecular docking also authenticates the involvement of α2β2γ2L GABA-A receptors and GABA-T enzyme in the antinociceptive activities of 3-OH-2'-MeO6MF.

Protective effects of a probiotic-fermented germinated grain complex on neurotransmitters and sleep quality in sleep-deprived mice.

To explore the effects of probiotic fermentation products of germinated grains on cognitive and sleep improvement in mice with sleep deprivation induced by chlorophenylalanine (PCPA), and to provide theoretical and experimental basis for the development of natural products to alleviate insomnia. ELISA and high-performance liquid chromatography (HPLC) were used to determine the contents of γ-aminobutyric acid and L-theanine in fermentation products. Open Field Test was used to analyze the changes of emotional behavior between groups before and after intervention. ELISA was used to analyze the changes of hypothalamic serotonin, GABA, glutamate, and serum interleukin 6. 16S rRNA sequencing was used to analyze the changes of intestinal flora before and after the intervention of compound fermentation products. LC-MS/MS was used to analyze the changes of intestinal SCFAs before and after the intervention. The content of GABA and L-theanine in 7 L fermentation products was 12.555 μmol/L (1.295 mg/L) and 0.471 mg/mL by ELISA. Compared with the PCPA-induced Model group, the sleep duration of the KEY group was statistically significant (p < 0.0001). Compared with the PCPA-induced Model group, the number of crossing the central lattice in the KEY group was significantly increased, and the number of grooming was significantly reduced (all p < 0.05), suggesting that the anxiety behavior of the mice was improved. In addition, this study found that the compound fermentation products could significantly increase the content of neurotransmitters such as 5-HT, GABA and Glu in the hypothalamus of mice, reduce the content of inflammatory factors such as IL-6, IL-1β and TNF-α in serum, regulate the structure of intestinal flora and increase the content of short-chain fatty acids. Probiotic fermentation products of germinated grains can significantly improve sleep deprivation in PCPA mice, which may be related to regulating the levels of neurotransmitters and inflammatory factors, improving the structure of intestinal flora, and increasing the content of short-chain fatty acids. This study provides new candidates and research directions for the development of natural drugs to alleviate insomnia.

Neuroprotective effects of g-Aminobutyric acid-enriched germinated riceberry extract in cerebral ischemic reperfusion-induced cognitive impairment mice

This study investigates the neuroprotective effects of riceberry (RB) and germinated riceberry (GRB) extracts on cognitive impairment induced by cerebral ischemia-reperfusion (IR) injury. Our findings indicate that the germination process reduces total phenolic content and total antioxidant capacity, accompanied by a decline in antioxidant activity. However, the enriched γ-aminobutyric acid (GABA) content significantly increased in the GRB extract, reaching an 11.55-fold higher concentration than the RB extract. Male ICR mice were used in this study and received RB (500 mg/kg BW) or GRB (250 and 500 mg/kg BW) extracts for 28 days, with cerebral IR injury induced on day 21. Memory and learning were assessed using the Morris water maze on days 22–27 and novel object recognition on day 28. Both RB and GRB extracts improved spatial and recognition memory while reducing hippocampal malondialdehyde levels, indicating decreased oxidative stress. GRB demonstrated superior effects, displaying accelerated learning responses and enhanced retention of spatial memory. The study highlights the potential of GRB, attributed to its high GABA content, in mitigating cognitive impairment induced by cerebral IR injury. Further research is needed to explore the underlying mechanisms and optimize therapeutic applications.

The Influence of Soaking Condition and Germination on Antioxidant Activity, and Chemical Properties of White Waxy Corn

White waxy corn enjoys global popularity because of its appealing taste and distinctive texture. Although it serves as a dietary cornerstone in numerous regions, it is characterized by relatively modest nutritional content. The objective of this research is to investigate various soaking solutions (including citrate buffer pH 3.0, citrate buffer pH 3.0 with 0,5% vitamin B6, citrate buffer pH 3.0 with 0,5% vitamin B6 and 0,5% glutamic acid) and different germination periods (ranging from 0 to 96 hours) on the level of antioxidant activity, ɣ-aminobutyric acid (GABA), polyphenols, and protein in white waxy corn. The highest ABTS inhibition (66.8%) was achieved through the soaking process involving citrate buffer pH 3.0 combined with L-glutamic acid and vitamin B6 solution during 96-hour germination. In contrast, the highest GABA concentration (213.9 ppm) was attained using citrate buffer pH 3.0 for 96-hour germination. The highest protein content (3110.9 ppm) was observed after 72 hours of germination using a soaking solution of citrate buffer pH three combined with L-glutamic acid and vitamin B6. However, the highest polyphenol (5603.3 ppm) was obtained using citrate buffer pH three for 72 hours. Soaking and germination can improve the chemical composition and antioxidant activity of white waxy corn.

Neuronal Hyperactivity in the Hippocampus during the Early Stage of Streptozotocin-Induced Type 1 Diabetes in Mice

Introduction: Cognitive dysfunction due to reduced neuronal transmission in the brain is a major emerging complication in diabetes. However, recent neuroimaging studies have demonstrated non-linear changes including hyperactivity in the hippocampus during the early stage of diabetes. This study aimed to determine the changes in neuronal activity at a single-cell level in hippocampal CA1 pyramidal neurons in the early stage of streptozotocin-induced type 1 diabetes in mice. Methods: Whole-cell patch-clamp recordings from acute brain slices were performed in mice over 4 consecutive weeks following the induction of hyperglycaemia using streptozotocin. In addition, microdialysate was collected from CA1 area while the mice were in an arousal state. The concentrations of glutamate and GABA in the microdialysate were then measured using ultra-performance liquid chromatography with mass spectrometry. Results: CA1 neurons in streptozotocin-induced diabetic mice exhibited higher membrane potentials (p = 0.0052), higher frequency of action potentials (p = 0.0052), and higher frequency of spontaneous excitatory post-synaptic currents (p = 0.037) compared with controls during the second week after hyperglycaemia was established. No changes in electrophysiological parameters were observed during the first, the third, and the fourth week. Moreover, the diabetic mice had higher extracellular glutamate concentration in CA1 area compared with controls (p = 0.021) during the second week after the initiation of diabetes. No change in the extracellular GABA concentration was observed. Conclusion: Our study demonstrated a temporary state of neuronal hyperactivity at the single-cell level in the hippocampal CA1 region during the early stage of diabetes. This neuronal hyperactivity might be related to altered glutamate metabolism and provide clues for future brain-target intervention.

Enhancement of γ-Aminobutyric Acid and the Characteristics of Nutrition and Function in White Quinoa through Ultrasound Stress at the Pre-Germination Stage.

The global production of quinoa has been increasing in recent years. In plant-based foods, ultrasound stress has received increasing attention, owing to its ability to enhance the production of primary and secondary metabolites. We studied the effects of ultrasonic stress at the pre-germination stage on the γ-aminobutyric acid (GABA) accumulation and characteristics of nutrition and function in quinoa. The results showed that ultrasonic conditions of 100 W for 4 min promoted an increase in GABA content by 9.15-fold, to 162.47 ± 6.69 mg/100 g·DW, compared to that of untreated quinoa, through promoting a 10.2% and 71.9% increase in the water absorption and glutamate decarboxylase activity of quinoa, respectively. Meanwhile, compared to untreated quinoa, ultrasonic stress at the pre-germination stage enhanced the total phenolic, total flavonoid, and total saponin contents of quinoa by 10.2%, 33.6%, and 90.7%, to 3.29 mg GA/g·DW, 104.0 mg RE/100 g·DW, and 7.13 mg/g, respectively, without decreasing its basic nutritional quality. Ultrasonic stress caused fissures on the surface of quinoa starch particles. Additionally, germination under ultrasonic stress increased the n3 polyunsaturated fatty acids by 14.4%. Furthermore, ultrasonic stress at the pre-germination stage promoted the scavenging of 2,2-diphenyl1-picrylhydrazyl radicals and inhibitions of α-amylase, α-glucosidase, and pancreatic lipase by 14.4%, 14.9%, 24.6%, and 20.0% in vitro, compared to untreated quinoa. The results indicated that the quinoa sprouted via ultrasonic stress could represent a promising method through which to develop nutritionally balanced whole grains rich in GABA, with hypoglycemic and hypolipidemic activities, which could provide theoretical support for the development of functional whole-grain foods based on quinoa.

Mepiquat chloride priming confers the ability of cotton seed to tolerate salt by promoting ABA-operated GABA signaling control of the ascorbate–glutathione cycle

BackgroundEnsuring that seeds germinate and emerge normally is a prerequisite for cotton production, esp. in areas with salinized soil. Priming with mepiquat chloride (MC) can promote seed germination and root growth under salt stress, but its mechanism has not been fully elucidated. In this study, physiological and biochemical experiments revealed that MC-priming promotes the tolerance of cotton seeds to salt stress by increasing the ability of antioxidant enzymes related to the ascorbate–glutathione (AsA-GSH) cycle to scavenge reactive oxygen species (ROS).ResultsResults revealed that treatment with inhibitors of abscisic acid (ABA) and γ-aminobutyric acid (GABA) biosynthesis reduced the positive effects of MC-priming. Similarly, MC-priming increased the contents of ABA and GABA under salt stress by stimulating the expression levels of GhNCED2 and GhGAD4 and the activity of calmodulin-binding (CML) glutamate decarboxylase (GAD). Further analysis showed that an inhibitor of ABA synthesis reduced the positive impacts of MC-priming on the content of GABA under salt stress, but the content of ABA was not affected by the GABA synthesis inhibitor. Furthermore, a multi-omics analysis revealed that MC-priming increased the abundance and phosphorylation levels of the proteins related to ABA signaling, CML, and Ca2+ channels/transporters in the MC-primed treatments, which resulted in increased oscillations in Ca2+ in the MC-primed cotton seeds under salt stress.ConclusionIn summary, these results demonstrate that MC-mediated ABA signaling operates upstream of the GABA synthesis generated by GAD by activating the oscillations of Ca2+ and then enhancing activity of the AsA-GSH cycle, which ensures that cotton seeds are tolerant to salt stress.

Increased cortical inhibition following brief motor memory reactivation supports reconsolidation and overnight offline learning gains.

Practicing motor skills stabilizes and strengthens motor memories by repeatedly reactivating and reconsolidating them. The conventional view, by which a repetitive practice is required for substantially improving skill performance, has been recently challenged by behavioral experiments, in which even brief reactivations of the motor memory have led to significant improvements in skill performance. However, the mechanisms which facilitate brief reactivation-induced skill improvements remain elusive. While initial memory consolidation has been repeatedly associated with increased neural excitation and disinhibition, reconsolidation has been shown to involve a poorly understood mixture of both excitatory and inhibitory alterations. Here, we followed a 3-d reactivation-reconsolidation framework to examine whether the excitatory/inhibitory mechanisms which underlie brief reactivation and repetitive practice differ. Healthy volunteers practiced a motor sequence learning task using either brief reactivation or repetitive practice and were assessed using ultrahigh field (7T) magnetic resonance spectroscopy at the primary motor cortex (M1). We found that increased inhibition (GABA concentrations) and decreased excitation/inhibition (glutamate/GABA ratios) immediately following the brief reactivation were associated with overnight offline performance gains. These gains were on par with those exhibited following repetitive practice, where no correlations with inhibitory or excitatory changes were observed. Our findings suggest that brief reactivation and repetitive practice depend on fundamentally different neural mechanisms and that early inhibition-and not excitation-is particularly important in supporting the learning gains exhibited by brief reactivation.

Reduced GABA concentration in patients with white matter hyperintensities.

To investigate potential alterations of white matter hyperintensities (WMHs) on J-edited MR spectroscopy (MRS) measures of the primary inhibitory neurotransmitter γ-aminobutyric acid (GABA). Twenty-four WMHs patients and 20 healthy controls (HCs) were recruited to undergo magnetic resonance spectroscopy (MRS) scan at 3T from voxels in left centrum semiovale white matter, using the MEGA point resolved spectroscopy (MEGA-PRESS) technique with the MATLAB-based Gannet tool to estimate GABA+ co-edited macromolecule (GABA+) levels and using Tarquin software to estimate levels of glutamate + glutamine (Glx), total N-acetylaspartate (tNAA), total choline (tCho), and total creatine (tCr). Independent t-tests or Mann-Whitney U-tests were used to test group differences between WMHs and HCs. Additionally, WMHs patients were divided into mild and moderate-severe WMHs subgroup according to the Fazekas scale. Analysis of variance (ANOVA) and post-hoc tests were used among WMHs subgroups and HCs. We found there was a significant reduction in GABA+ levels (p = 0.018) in WMHs patients compared with healthy controls. In subgroup analyses, there was also a significant reduction of GABA+ levels in moderate-severe WMHs subgroup (p = 0.037) and mild WMHs subgroup (p = 0.047) when compared to HCs. Besides, the moderate-severe WMHs subgroup had significantly higher levels of tCho compared with healthy controls (p = 0.019). In conclusion, reduced GABA+ levels in WMHs patients and elevated tCho levels in moderate-severe WMHs were observed when compared with HCs. These results demonstrate that abnormalities of the GABAergic system and choline metabolism may contribute to the pathogenesis of WMHs.

Supplementation with high-GABA-producing Lactobacillus plantarum L5 ameliorates essential tremor triggered by decreased gut bacteria-derived GABA

BackgroundThe γ-aminobutyric acid (GABA) hypothesis posits a role of GABA deficiency in the central nervous system in the pathogenesis and progression of essential tremor (ET). However, the specific causative factor for GABA deficiency is not clear. The gut microbiota in mammals has recently been considered as a significant source of GABA. Furthermore, the GABA-based signals originating from the intestine can be transmitted to the brain through the “enteric nervous system–vagus nerve–brain” axis. However, the plausible contribution of gut microbiota to ET seems inspiring but remains obscure.MethodsFecal samples from patients with ET and healthy controls were examined by metagenomic sequencing to compare the composition of gut microbiota and the expression of genes involved in GABA biosynthesis. The impact of gut microbiota on ET was explored through transplantation of fecal microbiota from patients with ET into the murine ET model. Lactic acid bacteria producing high amounts of GABA were identified through whole-genome sequencing and ultra-performance liquid chromatography-tandem mass spectrometry. Subsequently, mice were treated with the high-GABA-producing strain Lactobacillus plantarum L5. Tremor severity, behavioral tests, pro-inflammatory cytokines, GABA concentration, and gut microbiota composition were examined in these mice.ResultsThe gut microbiota of patients with ET demonstrated an impaired GABA-producing capacity and a reduced fecal GABA concentration. Transplantation of the gut microbiota from patients with ET induced an extension of tremor duration and impaired mobility in the murine model of ET. L5 exhibited an augmented GABA-producing capacity, with the De Man-Rogosa-Sharpe culture broth containing 262 mg/l of GABA. In addition, administration of L5 significantly decreased the tremor severity and enhanced the movement capability and grasping ability of ET mice. In vivo mechanistic experiments indicated that L5 reshaped the gut microbial composition, supplemented the mucosa-associated microbiota with GABA-producing capacity, increased the GABA concentrations in the cerebellum, and diminished inflammation in the central nervous system.ConclusionsThese findings highlight that deficiency of GABA-producing gut microbes plays an essential role in the pathogenesis of ET and that L5 is a promising candidate for treating ET.

Synchrony in auditory 40-Hz gamma oscillations increases in older age and correlates with hearing abilities and cortical GABA levels

Abstract Synchronized 40-Hz gamma oscillations in specific sensory and higher-order thalamocortical networks provide a neural mechanism for feature binding. Aging-related changes in gamma oscillations may cause deficits in auditory feature binding, contributing to impaired speech-in-noise perception. Gamma synchrony is controlled through inhibitory mechanisms mediated by the neurotransmitter γ-aminobutyric acid (GABA), which has been shown to decline in aging. This study investigated aging-related changes in gamma oscillations and how they relate to auditory function and cortical GABA levels. Magnetoencephalograms of 40-Hz auditory steady-state responses (ASSRs) were recorded in young and older adults by presenting amplitude-modulated tones in quiet and mixed with concurrent multi-talker babble noise. Responses in the quiet condition had longer latencies and more prominent amplitudes, indicating the 40-Hz ASSRs in noise were dominated by a sensory component and in quiet by a component involved in higher-order processing. The ASSR amplitudes increased in older adults under both stimulus conditions. However, larger ASSR amplitudes were associated with more severe hearing and speech-in-noise loss only in the noise condition. This suggests the aging-related increase in synchrony of sensory gamma oscillations has a detrimental effect on auditory processing. It may cause increased interference between competing sounds in the central auditory system, making it difficult for the aging auditory system to separate speech features from noise and bind them into a distinct perceptual object. Also in older adults, larger amplitudes of the 40-Hz ASSRs in the quiet condition were associated with higher left auditory cortex GABA concentrations measured with magnetic resonance spectroscopy, supporting GABA’s role in internally generated gamma synchrony in aging.

Enhancing Nutritional Profile of Pasta: The Impact of Sprouted Pseudocereals and Cushuro on Digestibility and Health Potential.

We hypothesized that optimizing the formulation of pasta by incorporating sprouted pseudocereal flours, specifically quinoa (Chenopodium quinoa Willd) or kiwicha (Amaranthus caudatus L.) and cushuro (Nostoc sphaericum Vaucher ex Bornet & Flahault) flours, could offer the potential to simultaneously enhance nutritional quality and health-promoting properties in pasta. In this study, our objective was to optimize the formulation of composite flour (a ternary blend of wheat, sprouted pseudocereal, and cushuro flours) using a mixture composite design to maximize total soluble phenolic compounds (TSPC), γ-aminobutyric acid (GABA), antioxidant activity, and mineral bioaccesilability by reducing phytic acid (PA) content. Two optimal formulations were identified: one consisting of 79% wheat flour (WF), 13% SQF, and 8% CuF (oPQC), and the other composed of 70% WF, 15% SKF, and 15% CuF (oPKC). These optimized pastas exhibited reduced starch content and notably higher levels of total dietary fiber (1.5-3.61-fold), protein (1.16-fold), fat (1.3-1.5-fold), ash (2.2-2.7-fold), minerals (K, Na, Fe, Zn, Mg, Mn, and Ca), PA (3-4.5-fold), TSPC (1.3-1.9-fold), GABA (1.2-2.6-fold), and ORAC (6.5-8.7-fold) compared to control pasta (100% WF). Notably, the glycemic index of oPQC (59.8) was lower than that of oPKC (54.7) and control pasta (63.1). The nutritional profile of the optimized pasta was largely retained after cooking, although some significant losses were observed for soluble dietary fiber (18.2-44.0%), K (47.5-50.7%), Na (42.5-63.6), GABA (41.68-51.4%), TSPC (8-18%), and antioxidant activity (45.4-46.4%). In vitro digestion of cooked oPQC and oPKC demonstrated higher bioaccessible content of GABA (6.7-16.26 mg/100 g), TSPC (257.7-261.8 mg GAE/100 g), Ca (58.40-93.5 mg/100 g), and Fe (7.35-7.52 mg/100 g), as well as antioxidant activity (164.9-171.1 µmol TE/g) in intestinal digestates compared to control pasta. These findings suggest that the incorporation of sprouted pseudocereals and cushuro flour offers a promising approach to enhance the nutritional quality and bioactive content of wheat-based pasta, potentially providing health benefits beyond traditional formulations.

Investigating the effects of aerobic exercise primed anodal transcranial direct current stimulation on γ‐aminobutyric acid concentrations in mild vascular cognitive impairment

AbstractBackgroundMild vascular cognitive impairment (mVCI) is characterized by minor deficits in cognition and memory due to underlying vascular pathology. Anodal transcranial direct current stimulation (atDCS), a non‐invasive neuromodulation technique, has been demonstrated to improve cognition. The effects of atDCS have been suggested to be mediated by γ‐aminobutyric acid (GABA)–a major inhibitory neurotransmitter associated with cerebral perfusion and oxygenation, and cognition and memory. However, previous studies have reported mixed results regarding changes in GABA concentrations following atDCS. Physical activity has been reported to increase cortical GABA levels, and in particular, aerobic exercise (AE) is associated with improved cognition in older adults. Preliminary data from an ongoing trial (EXPRESS‐V) was used to evaluate whether GABA concentration in the motor cortex was altered following AE and/or atDCS and whether this was associated with changes in global cognition in mVCI.MethodIn this double‐blind, randomized clinical trial, participants received one of four interventions for two weeks: AE and atDCS, AE and sham atDCS, exercise education and atDCS, or exercise education and sham atDCS. mVCI was determined based on a modified Gorelick criteria. At baseline and endpoint, GABA concentration in the motor cortex was measured using magnetic resonance spectroscopy and quantified with the Mescher‐Garwood point resolved spectroscopy pulse sequence, and global cognition was assessed using the Montreal Cognitive Assessment. Wilcoxon signed rank test was used to determine changes in GABA concentrations (ΔGABA). Spearman correlation was used to determine the association between ΔGABA and changes in global cognition (ΔMoCA).ResultTen participants have enrolled so far, with nine participants having completed the study (22.2% female, age = 66.4(9.8), years of education = 8.8(3.4), 55.6% White, baseline MoCA score = 22.8(3.1)). To date, ΔGABA was insignificant between baseline and endpoint (Z = 23.0, p = 0.953). However, a positive trend between ΔGABA and ΔMoCA was observed (ρ = 0.650, p = 0.058).ConclusionPreliminary results from nine participants showed a positive trend between ΔGABA and ΔMoCA. Since the trial is ongoing, with the target of recruiting 80 participants by 2024, analyses on unblinded data upon study completion will determine whether AE and atDCS leads to greater ΔGABA, and whether this is accompanied by greater ΔMoCA in mVCI.

CmCML11 interacts with CmCAMTA5 to enhance γ-aminobutyric acid (GABA) accumulation by regulating GABA shunt in fresh-cut cantaloupe

The effect of calcium chloride (CaCl2) treatment on γ-aminobutyric acid (GABA) accumulation in fresh-cut cantaloupe and the involved mechanisms were investigated. The result showed that 1% (w/v) CaCl2 treatment increased GABA content and activities of glutamate decarboxylase (GAD) and succinate semialdehyde dehydrogenase (SSADH), while decreased glutamate (Glu) content and GABA transaminase (GABA-T) activities in fresh-cut cantaloupe. CmCML11 and CmCAMTA5 expressions of CaCl2-treated fruit increased by 187.4% and 165.6% than control fruit in the initial 6 h. Besides, expressions of GABA shunt genes, including CmGAD1, CmGAD2, CmGABA-T and CmSSADH were also up-regulated by CaCl2 treatment during early storage. Moreover, acting as a transcriptional activator, CmCAMTA5 could bind to the CG-box in promoters of CmGAD1, CmGABA-T and CmSSADH and activate their transcription. Furthermore, the interaction between CmCML11 and CmCAMTA5 could enhance the transcriptional activation on GABA shunt genes which were regulated by CmCAMTA5. Collectively, our findings revealed that CaCl2 treatment promoted GABA accumulation in fresh-cut cantaloupe via the combined effect of CmCML11 and CmCAMTA5 in the regulation of expressions of CmGAD1, CmGABA-T, and CmSSADH in GABA shunt.

Low-temperature acclimation related with developmental regulations of polyamines and ethylene metabolism in wheat recombinant inbred lines

Winter survival is determined by complicated developmental regulations enabling wheat to adjust their transcriptome and metabolome to develop low temperature (LT) tolerance. The aim of the study was to clarify the metabolic responses developmentally regulated in six F6 recombinant inbred lines from a cross between Pishtaz (spring parent) and Mironovskaya 808 (winter parent). Spring genotypes, including pishtaz, RILs 4006 and 4014 showed lower LT tolerance, PAs (except the spermin), GABA and proline contents and DPPH• scavenging capacity. In these genotypes, genes and enzymes involved in the pathways of PAs and GABA degradation and ethylene biosynthesis were more active than other genotypes. RILs 4012 and 4016 with short vernalization displayed higher tolerance and lower H2O2 content compared to Pishtaz. Strong vernalization requirements in winter and facultative genotypes (Mironovskaya 808 parent and RILs 4003 and 4005) results in up-regulation of the metabolites and genes involved in PAs and GABA biosynthesis pathways (particularly when vernalization fulfillment occurred) to establish high tolerance as compared to genotypes without vernalization requirement. LT tolerance in all genotypes significantly decreased after vernalization fulfillment in February. Results indicated that LT tolerance was partly validated from developmental regulation of PAs, GABA, and ethylene metabolism during venalization and LT acclimation.