Showing papers on "gamma-Aminobutyric acid published in 2022"

GABAergic System Dysfunction in Autism Spectrum Disorders

Abstract: Autism spectrum disorder (ASD) refers to a series of neurodevelopmental diseases characterized by two hallmark symptoms, social communication deficits and repetitive behaviors. Gamma-aminobutyric acid (GABA) is one of the most important inhibitory neurotransmitters in the central nervous system (CNS). GABAergic inhibitory neurotransmission is critical for the regulation of brain rhythm and spontaneous neuronal activities during neurodevelopment. Genetic evidence has identified some variations of genes associated with the GABA system, indicating an abnormal excitatory/inhibitory (E/I) neurotransmission ratio implicated in the pathogenesis of ASD. However, the specific molecular mechanism by which GABA and GABAergic synaptic transmission affect ASD remains unclear. Transgenic technology enables translating genetic variations into rodent models to further investigate the structural and functional synaptic dysregulation related to ASD. In this review, we summarized evidence from human neuroimaging, postmortem, and genetic and pharmacological studies, and put emphasis on the GABAergic synaptic dysregulation and consequent E/I imbalance. We attempt to illuminate the pathophysiological role of structural and functional synaptic dysregulation in ASD and provide insights for future investigation.

GABA Levels in the Midcingulate Cortex and Clozapine Response in Patients with Treatment‐Resistant Schizophrenia: A 1 H‐MRS Study

Abstract: Background Gamma-Aminobutyric Acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. GABAergic dysfunction has been implicated in the pathophysiology of schizophrenia. Clozapine, the only approved drug for treatment-resistant schizophrenia (TRS), involves the GABAergic system as one of its targets. However, no studies have investigated the relationship between brain GABA levels, as measured by proton magnetic resonance spectroscopy (1H-MRS), and clozapine response in patients with TRS. Methods This study enrolled patients with TRS who did not respond to clozapine (ultra-resistant schizophrenia: URS) and who responded to clozapine (non-URS), patients with schizophrenia who responded to first-line antipsychotics (first-line responders: FLR), and healthy controls (HCs). We measured GABA levels in the midcingulate cortex (MCC) using 3T 1H-MRS and compared these levels among the groups. The associations between GABA levels and symptom severity were also explored within the patient groups. Results A total of 98 participants (URS: n = 22; non-URS: n = 25; FLR: n = 16; HCs: n = 35) completed the study. We found overall group differences in MCC GABA levels (F(3,86) = 3.25, P = 0.04). Specifically, patients with URS showed higher GABA levels compared to those with non-URS (F(1,52) = 8.40, P = 0.03, Cohen's d = 0.84). MCC GABA levels showed no associations with any of the symptom severity scores within each group or the entire patient group. Conclusion Our study is the first to report elevated GABA levels in the MCC in patients with schizophrenia resistant to clozapine treatment compared with those responsive to clozapine. Longitudinal studies are required to evaluate if GABA levels are a suitable biomarker to predict clozapine resistance.

Gamma‐aminobutyric acid (GABA) levels in the midcingulate cortex and clozapine response in patients with treatment‐resistant schizophrenia: A proton magnetic resonance spectroscopy (1H‐MRS) study

Abstract: Gamma‐Aminobutyric Acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. GABAergic dysfunction has been implicated in the pathophysiology of schizophrenia. Clozapine, the only approved drug for treatment‐resistant schizophrenia (TRS), involves the GABAergic system as one of its targets. However, no studies have investigated the relationship between brain GABA levels, as measured by proton magnetic resonance spectroscopy (1H‐MRS), and clozapine response in patients with TRS.

Probiotic Properties and Optimization of Gamma-Aminobutyric Acid Production by Lactiplantibacillus plantarum FBT215

Abstract: Gamma-aminobutyric acid (GABA) improves various physiological illnesses, including diabetes, hypertension, depression, memory lapse, and insomnia in humans. Therefore, interest in the commercial production of GABA is steadily increasing. Lactic acid bacteria (LAB) have widely been reported as a GABA producer and are safe for human consumption. In this study, GABA-producing LAB were preliminarily identified and quantified via GABase assay. The acid and bile tolerance of the L. plantarum FBT215 strain were evaluated. The one-factor-at-a-time (OFAT) strategy was applied to determine the optimal conditions for GABA production using HPLC. Response surface methodology (RSM) with Box-Behnken design was used to predict the optimum GABA production. The strain FBT215 was shown to be acid and bile tolerant. The optimization of GABA production via the OFAT strategy resulted in an average GABA concentration of 1688.65 ± 14.29 μg/ml, while it was 1812.16 ± 23.16 μg/ml when RSM was applied. In conclusion, this study provides the optimum culture conditions for GABA production by the strain FBT215 and indicates that L. plantarum FBT215 is potentially promising for commercial functional probiotics with health claims.

Production of Gamma-Aminobutyric Acid by Levilactobacillus brevis CD0817 by Coupling Fermentation with Self-Buffered Whole-Cell Catalysis

Abstract: There is a recent trend of using lactic acid bacteria for the production of gamma-aminobutyric acid (GABA). This study described a method that combines fermentation and self-buffered whole-cell catalysis for the efficient production of GABA using Levilactobacillus brevis CD0817. Upon the completion of GABA fermentation, cells were recovered to conduct whole-cell catalysis by which the substrate L-glutamic acid was catalytically decarboxylated to GABA. L-glutamic acid itself maintained the acidity essential for decarboxylation. To maximize the whole-cell catalysis ability, the effects of the cell culture method, catalysis temperature, catalysis time, cell concentration, and L-glutamic acid dosage were investigated. The results illustrate that the cells that were cultivated for 16 h in a fermentation medium supplemented with 20.0 g/L of glucose were the most suitable for the whole-cell catalytic production of GABA. At 16 h, the fermentative GABA content reached 204.2 g/L. Under optimized whole-cell catalytic conditions (temperature 45.0 °C, time 12.0 h, wet cells 25.0 g/L, and L-glutamic acid 120.0 g/L), 85.1 g/L of GABA was obtained, with 3.7 ± 0.9 g/L of substrate residue. GABA was recovered from the system by sequentially performing rotary vacuum evaporation, precipitation with ethanol, filtration with filter paper, and drying. The purity of the GABA product reached 97.1%, with a recovery rate of 87.0%. These data suggest that the proposed method has potential applications in the production of GABA.

Gamma-aminobutyric acid and glutamate/glutamine levels in the dentate nucleus and periaqueductal gray with episodic and chronic migraine: a proton magnetic resonance spectroscopy study

Abstract: Abstract Background The pathogenesis of migraine chronification remains unclear. Functional and structural magnetic resonance imaging studies have shown impaired functional and structural alterations in the brains of patients with chronic migraine. The cerebellum and periaqueductal gray (PAG) play pivotal roles in the neural circuits of pain conduction and analgesia in migraine. However, few neurotransmitter metabolism studies of these migraine-associated regions have been performed. To explore the pathogenesis of migraine chronification, we measured gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels in the dentate nucleus (DN) and PAG of patients with episodic and chronic migraine and healthy subjects. Methods Using the MEGA-PRESS sequence and a 3-Tesla magnetic resonance scanner (Signa Premier; GE Healthcare, Chicago, IL, USA), we obtained DN and PAG metabolite concentrations from patients with episodic migraine ( n = 25), those with chronic migraine ( n = 24), and age-matched and sex-matched healthy subjects ( n = 16). Patients with chronic migraine were further divided into those with ( n = 12) and without ( n = 12) medication overuse headache. All scans were performed at the Beijing Tiantan Hospital, Capital Medical University. Results We found that patients with chronic migraine had significantly lower levels of GABA/water (p = 0.011) and GABA/creatine (Cr) (p = 0.026) in the DN and higher levels of Glx/water (p = 0.049) in the PAG than healthy controls. In all patients with migraine, higher GABA levels in the PAG were significantly associated with poorer sleep quality (GABA/water: r = 0.515, p = 0.017, n = 21; GABA/Cr: r = 0.522, p = 0.015, n = 21). Additionally, a lower Glx/Cr ratio in the DN may be associated with more severe migraine disability ( r = -0.425, p = 0.055, n = 20), and lower GABA/water ( r = -0.424, p = 0.062, n = 20) and Glx/Water ( r = -0.452, p = 0.045, n = 20) may be associated with poorer sleep quality. Conclusions Neurochemical levels in the DN and PAG may provide evidence of the pathological mechanisms of migraine chronification. Correlations between migraine characteristics and neurochemical levels revealed the pathological mechanisms of the relevant characteristics.

Screening of gamma-aminobutyric acid-producing lactic acid bacteria and the characteristic of glutamate decarboxylase from Levilactobacillus brevis F109-MD3 isolated from kimchi

Abstract: Abstract Aims This study aimed to screen the γ-aminobutyric acid (GABA)-producing lactic acid bacteria (LAB) from kimchi, and investigate the glutamate decarboxylase (GAD) activity of the highest GABA-producing strain. Methods and Results Seven strains of LAB were screened from kimchi with GABA-producing activity. Strain Levilactobacillus brevis F109-MD3 showed the highest GABA-producing ability. It produced GABA at a concentration of 520 mmol l−1 with a 97.4% GABA conversion rate in MRS broth containing 10% monosodium glutamate for 72 h. The addition of pyridoxal 5’-phosphate had no significant effect on the GAD activity of L. brevis F109-MD3. The optimal pH range of GAD was 3.0–5.0 and the optimal temperature was 65°C. The D value of GAD at 50, 60 and 70°C was 7143, 971 and 124 min respectively and Z value was 11.36°C. Conclusions Seven strains isolated from kimchi, especially F109-MD3, showed high GABA-production ability even in the high concentrations of MSG at 7.5% and 10%. The GAD activity showed an effective broad pH range and higher optimal temperature. Significance and Impact of the Study These seven strains could be potentially useful for food-grade GABA production and the development of healthy foods.

Relative bioavailability and plasma kinetics of oral gamma-aminobutyric acid (GABA) and its precursor glutamate from tomato in healthy men

Abstract: Gamma-aminobutyric acid (GABA) and its precursor glutamate play signaling roles in a range of tissues. Both function as neurotransmitters in the central nervous system, but they also modulate pancreatic and...

Effects of pulsed light on germination and gamma-aminobutyric acid synthesis in brown rice.

Abstract: This study observed the effects of pulsed light (PL) on the germination and gamma-aminobutyric acid (GABA) production of brown rice and analyzed the correlations among glutamic acid (Glu) content, glutamate decarboxylase (GAD) activity, and GABA content in germinating brown rice. Both germination and GABA content were increased by exposure to PL, and this effect was evident when brown rice was exposed to PL immediately after being soaked. The PL group had significantly higher Glu and GABA content than the control check (CK) group which was unexposed to PL during the germination of brown rice. Glu content peaked at 18 h and GABA peaked at 24h in the PL group, which were 12 h and 6 h earlier than the CK group, respectively. GAD activity of the PL group peaked 12 h after germination, 6 h earlier than the CK group. PL exposure also increased the free amino acid content in the earliest stage of brown-rice germination. During brown-rice germination, the production of GABA is regulated by GAD activity and is significantly positively correlated with Glu content. PL treatment had a significant effect on GAD activity and Glu content during the germination process of brown rice and helped to increase its GABA content. PRACTICAL APPLICATION: This study has shown that pulsed light exposure is an efficient and stable processing method for producing brown rice with high GABA. This will provide a new direction for developing novel germination grain foods.

Critical Optimized Conditions for Gamma-Aminobutyric Acid (GABA)-Producing Tetragenococcus Halophilus Strain KBC from a Commercial Soy Sauce Moromi in Batch Fermentation

Abstract: Gamma-aminobutyric acid (GABA) has several health-promoting qualities, leading to a growing demand for natural GABA production via microbial fermentation. The GABA-producing abilities of the new Tetragenococcus halophilus (THSK) isolated from a commercial soy sauce moromi were proven in this investigation. Under aerobic conditions, the isolate produced 293.43 mg/L of GABA after 5 days of cultivation, compared to 217.13 mg/L under anaerobic conditions. Critical parameters such as pH, monosodium glutamate (MSG), and sodium chloride (NaCl) concentrations were examined to improve GABA yield. MSG had the most significant impact on GABA and GABA synthesis was not suppressed even at high NaCl concentrations. Data showed that a pH of 8, MSG content of 5 g/L, and 20% NaCl were the best culture conditions. The ultimate yield was improved to 653.101 mg/L, a 2.22-fold increase (293.43 mg/L). This design shows that the bacteria THSK has industrial GABA production capability and can be incorporated into functional food.

The influence of a tomato food matrix on the bioavailability and plasma kinetics of oral gamma-aminobutyric acid (GABA) and its precursor glutamate in healthy men.

Abstract: Gamma-aminobutyric acid (GABA) and its precursor glutamate play signaling roles in a range of tissues. Both function as neurotransmitters in the central nervous system, but they also modulate pancreatic and immune functioning, for example. Besides endogenous production, both compounds are found in food products, reaching relatively high levels in tomatoes. Recent studies in rodents suggest beneficial effects of oral GABA on glucose homeostasis and blood pressure. However, the bioavailability from food remains unknown. We studied the bioavailability of GABA and glutamate from tomatoes relative to a solution in water. After a fasting blood sample was taken, eleven healthy men randomly received 1 liter of 4 different drinks in a cross-over design with a one-week interval. The drinks were a solution of 888 mg L-1 GABA, a solution of 3673 mg L-1 glutamate, pureed fresh tomatoes and plain water as the control. Following intake, 18 blood samples were taken at intervals for 24 hours. Plasma GABA and glutamate concentrations were determined by ultra-pressure liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Fasting plasma GABA and glutamate concentrations were found to be 16.71 (SD 2.18) ng mL-1 and 4626 (SD 1666) ng mL-1, respectively. Fasting GABA levels were constant (5.8 CV%) between individuals, while fasting glutamate levels varied considerably (23.5 CV%). GABA from pureed tomatoes showed similar bioavailability to that of a solution in water. For glutamate, the absorption from pureed tomatoes occurred more slowly as seen from a longer tmax (0.98 ± 0.14 h vs. 0.41 ± 0.04 h, P = 0.003) and lower Cmax (7815 ± 627 ng mL-1vs. 16 420 ± 2778 ng mL-1, P = 0.006). These data suggest that GABA is bioavailable from tomatoes, and that food products containing GABA could potentially induce health effects similar to those claimed for GABA supplements. The results merit further studies on the bioavailability of GABA from other food products and the health effects of GABA-rich diets. The clinical trial registry number is NCT04086108 (https://clinicaltrials.gov/ct2/show/NCT04303468).

Exogenous Gamma-Aminobutyric Acid Application Induced Modulations in the Performance of Aromatic Rice Under Lead Toxicity

Abstract: Gamma-aminobutyric acid (GABA) is a non-protein amino acid and has a multi-functional role in abiotic stress tolerance. A pot experiment was conducted to assess the role of exogenous gamma-aminobutyric acid (GABA) application to modulate the growth, yield, and related physio-biochemical mechanisms in two aromatic rice cultivars, that is, Guixiangzhan (GXZ) and Nongxiang 18 (NX-18), under Pb toxic and normal conditions. The experimental treatments were comprised of Ck: without Pb and GABA (control), GABA: 1 mM GABA is applied under normal conditions (without Pb), Pb + GABA: 1 mM GABA is applied under Pb toxicity (800 mg kg−1 of soil), and Pb= only Pb (800 mg kg−1 of soil) is applied (no GABA). The required concentrations of GABA were applied as a foliar spray. Results revealed that Pb stress induced oxidative damage in terms of enhanced malondialdehyde (MDA), electrolyte leakage (EL), and H2O2 contents, while exogenous GABA application improved leaf chlorophyll, proline, protein and GABA contents, photosynthesis and gas exchange, and antioxidant defense under Pb toxicity in both rice cultivars. Moreover, glutamine synthetase (GS) and nitrate reductase (NR) activities were variably affected due to GABA application under Pb stress. The yield and related traits, that is, productive tillers/pot, grains/panicle, filled grain %, 1,000-grain weight, and grain yield were 13.64 and 10.29, 0.37% and 2.26%, 3.89 and 19.06%, 7.35 and 12.84%, and 17.92 and 40.56 lower under Pb treatment than Pb + GABA for GXZ and NX-18, respectively. Furthermore, exogenous GABA application in rice reduced Pb contents in shoot, leaves, panicle, and grains compared with Pb-exposed plants without GABA. Overall, GXZ performed better than NX-18 under Pb toxic conditions.

Gamma Aminobutyric Acid (GABA) Enrichment in Plant-Based Food – A Mini Review

Abstract: Gamma aminobutyric acid (GABA) is a four-C, nonprotein amino acid that plays a significant role in human nervous system. Research on GABA in medical and pharmaceutical fields has uncovered some of the exciting physiological benefits of GABA to humans. This mini review reports three main biosynthetic pathways of GABA in plants, that involved either decarboxylation of glutamate, degradation of polyamine or non-enzymatic conversion of proline into GABA. GABA is naturally present in foods, as part of the essential metabolic processes or interaction between the organism with the environment. In comparison, plant-based foods contain relatively lower amount of GABA than the animal-based foods. Generally, dietary GABA intake through plant-based diet is insignificance due to the trace amount present, except for materials that have been manipulated via germination and/or fermentation. However, data on GABA stability post-processing and during storage, its bioavailability and clinical implications upon consumption is relatively scarce in the literature, and therefore this warrant further investigation.

Postpartum State, but Not Maternal Caregiving or Level of Anxiety, Increases Medial Prefrontal Cortex GAD65 and vGAT in Female Rats

Abstract: Upregulation of the inhibitory neurotransmitter, GABA, is involved in many of the behavioral differences between postpartum and nulliparous female rodents. This is evidenced by studies showing that pharmacological blockade of GABAergic activity impairs maternal caregiving and postpartum affective behaviors. However, the influence of motherhood on the capacity for GABA synthesis or release in the medial prefrontal cortex (mPFC; brain region involved in many social and affective behaviors) is not well-understood. Western blotting was used to compare postpartum and nulliparous rats in protein levels of the 65-kD isoform of glutamic acid decarboxylase (GAD65; synthesizes most GABA released from terminals) and vesicular GABA transporter (vGAT; accumulates GABA into synaptic vesicles for release) in the mPFC. We found that postpartum mothers had higher GAD65 and vGAT compared to virgins, but such differences were not found between maternally sensitized and non-sensitized virgins, indicating that reproduction rather than just the display of maternal caregiving is required. To test whether GAD65 and vGAT levels in the mPFC were more specifically related to anxiety-related behavior within postpartum mothers, we selected 8 low-anxiety and 8 high-anxiety dams based on their time spent in the open arms of an elevated plus maze on postpartum day 7. There were no significant differences between the anxiety groups in either GAD65 or vGAT levels. These data further indicate that frontal cortical GABA is affected by female reproduction and more likely contributes to differences in the display of socioemotional behaviors across, but not within, female reproductive state.

Application of Enterococcus malodoratus SJC25 for the Manufacture of Whey-Based Beverage Naturally Enriched with GABA

Abstract: Gamma-aminobutyric acid (GABA) is used as a dietary supplement because of its health-promoting properties. However, concern over the use of synthetic products has increased the demand for foods that are naturally fortified with GABA. In addition, excess whey is a major concern for the dairy industry due to the high cost of treating it. Here, we report the use of a novel Enterococcus malodoratus strain isolated from cheese to produce sweet whey beverages naturally enriched with GABA. After the screening of cheese isolates, E. malodoratus strains were identified as high GABA producers. One beverage was prepared from pasteurized sweet whey enriched in glutamic acid and E. malodoratus SJC25. The fermented beverages were supplemented with a fruit preparation and subjected to chemical, microbiological and sensory analysis. The bacterial counts and GABA content were maintained until storage at 4 °C for 14 days. High conversion rates of glutamic acid to GABA (50–71%) were obtained in the beverages. The GABA content in whey-based beverages reached 250–300 mg/100 mL, which is equivalent to the content of commercially available GABA supplements. The beverages received a positive rating (4/5) by the taste panel. To our knowledge, this is the first report on E. malodoratus as a potential GABA producer.

Dietary Gamma-Aminobutyric Acid (GABA) Induces Satiation by Enhancing the Postprandial Activation of Vagal Afferent Nerves

Abstract: Gamma-aminobutyric acid (GABA) is present in the mammalian brain as the main inhibitory neurotransmitter and in foods. It is widely used as a supplement that regulates brain function through stress-reducing and sleep-enhancing effects. However, its underlying mechanisms remain poorly understood, as it is reportedly unable to cross the blood–brain barrier. Here, we explored whether a single peroral administration of GABA affects feeding behavior as an evaluation of brain function and the involvement of vagal afferent nerves. Peroral GABA at 20 and 200 mg/kg immediately before refeeding suppressed short-term food intake without aversive behaviors in mice. However, GABA administration 30 min before refeeding demonstrated no effects. A rise in circulating GABA concentrations by the peroral administration of 200 mg/kg GABA was similar to that by the intraperitoneal injection of 20 mg/kg GABA, which did not alter feeding. The feeding suppression by peroral GABA was blunted by the denervation of vagal afferents. Unexpectedly, peroral GABA alone did not alter vagal afferent activities histologically. The coadministration of a liquid diet and GABA potentiated the postprandial activation of vagal afferents, thereby enhancing postprandial satiation. In conclusion, dietary GABA activates vagal afferents in collaboration with meals or meal-evoked factors and regulates brain function including feeding behavior.

Continuous theta-burst stimulation to the sensorimotor cortex affects contralateral gamma-aminobutyric acid level and resting-state networks

Abstract: Continuous theta-burst stimulation (cTBS) is a noninvasive repetitive brain stimulation protocol that suppresses the excitability of the primary motor cortex. It induces cerebral cortical inhibition by increasing inhibitory interneuronal excitability that is associated with increases in gamma-aminobutyric acid (GABA) concentration in the stimulated cortices. cTBS has been applied in the rehabilitation of stroke patients to modulate interhemispheric imbalance. However, the precise mechanisms of cTBS in remote brain areas remain uncertain. We evaluated cTBS-induced GABA level changes in bilateral sensorimotor cortices using GABA-edited magnetic resonance spectroscopy, alternations of motor evoked potentials (MEPs), and resting-state networks (RSNs) using resting-state functional magnetic resonance imaging in 24 healthy right-handed adults (mean age: 34.4 ± 5.0 years). GABA levels in the stimulated left hemisphere significantly increased from baseline (p = 0.013), which was comparable with those of previous reports. GABA levels in the unstimulated right hemisphere showed a trend decrease. cTBS induced a significant decrease in right hand-MEP amplitudes (22.06% ± 43.50%) from baseline (p = 0.026) in accordance with GABA concentrations. However, multiple RSNs, including the default mode and primary motor networks, did not show any obvious differences between pre- and post-stimulus comparisons in the sensorimotor network using the dual regression approach. These results suggest that cTBS simultaneously increases ipsilateral GABA in the stimulated left hemisphere and decreases contralateral GABA in the unstimulated right hemisphere. Neuromodulation following cTBS may be associated with the interhemispheric inhibition because of alterations in GABA levels between the stimulated and unstimulated cortices.

Exogenous gamma‐aminobutyric acid addition enhances porcine sperm acrosome reaction

Abstract: Abstract The widely used porcine artificial insemination procedure involves the use of liquid‐stored semen because it is difficult to control the quality of frozen–thawed porcine sperm. Therefore, there is a high demand for porcine semen. The control and enhancement of sperm function are required for the efficient reproduction of pigs. We previously reported that gamma‐aminobutyric acid (GABA) enhanced sperm capacitation and acrosome reaction in mice. In this study, we demonstrated the presence of GABAA receptors in porcine sperm acrosome. Furthermore, we investigated the GABA effects on porcine sperm function. We did not detect any marked effect of GABA on sperm motility and tyrosine phosphorylation of sperm proteins. However, GABA promoted acrosome reaction, which was suppressed by a selective GABAA receptor antagonist. GABA binds to GABAA receptors, resulting in chloride ion influx. We found that treatment with 1 μM GABA increased the intracellular concentration of chloride ion in the sperm. In addition, the GABA concentration effective in the acrosome reaction was correlated with the porcine sperm concentration. These results indicate that GABA and its receptors can act as modulators of acrosome reaction. This study is the first to report the effects of GABA on porcine sperm function.