High Concentrations Of GABA Research Articles

Factors promoting the release of picrotoxin from the trap in the GABA(A) receptor pore

Picrotoxin (PTX), a convulsant of plant origin, has been used in many studies as research tool. PTX is the open channel blocker of the GABAA receptor (GABAAR). Being in the pore, PTX initiates transfer of the channel to the closed state and thus it falls into the “trap”. The consequence of this PTX trapping is so-called aftereffect, i.e. continuation of the blockade of the GABA-induced chloride current (IGABA) after removal of PTX from the external solution. The present work shows that the positive allosteric modulators (PAMs) of the GABAA receptor, allopregnanolone (Allo) and zolpidem (Zolp) as well as a high concentration of GABA shortened the PTX aftereffect. Experiments were carried out on isolated Purkinje neurons of the rat cerebellum using the whole-cell patch-clamp method. IGABA was induced by applications of 5 μM GABA (EC30) for 1 s with 30 s intervals. 50 μM PTX completely blocked IGABA, and recovery upon PTX washout occurred with a time constant (τrec) of 20.2 min. 1 μM Allo reduced the blocking effect of PTX by 30% and accelerated the recovery of IGABA by almost 10 times (τrec = 2.4 min). 0.5 μM Zolp did not change the IGABA block in the presence of PTX but accelerated the recovery of IGABA by more than 3 times (τrec = 5.6 min). Increasing the GABA concentration to 20 μM did not change the blocking effect of PTX, but accelerated recovery by 6 times (τrec = 3.3 min). The mechanism of the shortening of the PTX aftereffect is presumably the expansion of the GABAAR pore in the presence of PAMs and a high concentration of the agonist and, as a consequence, the escape of PTX from the “trap”. The work describes new pharmacological properties of Allo and Zolp.

Betel quid: New insights into an ancient addiction.

The use of areca nuts (areca) in the form of betel quids constitutes the fourth most common addiction in the world, associated with high risk for oral disease and cancer. Areca is a complex natural product, making it difficult to identify specific components associated with the addictive and carcinogenic properties. It is commonly believed that the muscarinic agonist arecoline is at the core of the addiction. However, muscarinic receptor activation is not generally believed to support drug-taking behaviour. Subjective accounts of areca use include descriptions of both sedative and stimulatory effects, consistent with the presence of multiple psychoactive agents. We have previously reported partial agonism of α4-containing nicotinic acetylcholine receptors by arecoline and subsequent inhibition of those receptors by whole areca broth. In the present study, we report the inhibition of nicotinic acetylcholine receptors and other types of neurotransmitter receptors with compounds of high molecular weight in areca and the ability of low molecular weight areca extract to activate GABA and glutamate receptors. We confirm the presence of a high concentration of GABA and glutamate in areca. Additionally, data also indicate the presence of a dopamine and serotonin transporter blocking activity in areca that could account for the reported stimulant and antidepressant activity. Our data suggest that toxic elements of high molecular weight may contribute to the oral health liability of betel quid use, while two distinct low molecular weight components may provide elements of reward, and the nicotinic activity of arecoline contributes to the physical dependence of addiction.

Biosynthesis of γ-aminobutyric acid by lactic acid bacteria in surplus bread and its use in bread making.

AimsThe aim of this study was to investigate the effectiveness of bread as substrate for γ‐aminobutyric acid (GABA) biosynthesis, establishing a valorization strategy for surplus bread, repurposing it within the food chain.Methods and ResultsSurplus bread was fermented by lactic acid bacteria (LAB) to produce GABA. Pediococcus pentosaceus F01, Levilactobacillus brevis MRS4, Lactiplantibacillus plantarum H64 and C48 were selected among 33 LAB strains for the ability to synthesize GABA. Four fermentation experiments were set up using surplus bread as such, added of amylolytic and proteolytic enzymes, modifying the pH or mixed with wheat bran. Enzyme‐treated slurries led to the release of glucose (up to 20 mg g−1) and free amino acid, whereas the addition of wheat bran (30% of bread weight) yielded the highest GABA content (circa 800 mg kg −1 of dry weight) and was the most suitable substrate for LAB growth. The selected slurry was ultimately used as an ingredient in bread making causing an increase in free amino acids.ConclusionsBesides the high GABA concentration (148 mg kg −1 dough), the experimental bread developed in this study was characterized by good nutritional properties, highlighting the efficacy of tailored bioprocessing technologies as means to mitigate food wastage.Significance and Impact of StudyOur results represent a proof of concept of effective strategies to repurpose food industry side streams.

Are there profiles of cheeses with a high GABA and safe histamine content?

Some bacteria decarboxylate amino acids as a means of resisting acid stress. It is a mechanism commonly used by bacteria in fermented dairy products. The decarboxylation of histidine to histamine occurs frequently in some types of cheese, but high concentrations of histamine can be harmful to consumers. Not all amino acid decarboxylation products are, however, undesirable. GABA, the decarboxylation product of glutamate, has positive effects on human health. Although histamine and GABA accumulate in large quantities in many types of cheese, there is little information regarding their relationship, and that which is available is restricted to a few cheese varieties. The present work examines whether cheeses exist with high concentrations of GABA but safe concentrations of histamine. The GABA and histamine contents of 250 cheeses representing 143 European varieties were examined, and the technological, environmental and metabolic (TEM) traits governing their accumulation identified. Two TEM profiles were associated with high GABA contents and safe histamine concentrations. These findings could help the dairy industry select the best technological conditions for making GABA-rich, histamine-safe cheeses. • GABA and histamine were determined in 250 cheeses of 143 different varieties. • GABA (healthy) and histamine (toxic) can accumulate at high concentrations. • A positive correlation exists between GABA and histamine concentration. • Cheeses with high GABA and low histamine contents were identified. • The technological/environmental/metabolic profiles of these cheeses were recorded.

Temperature dependence of the microwave dielectric properties of gamma-aminobutyric acid

The GABA molecule is the major inhibitory neurotransmitter in the mammalian central nervous system. Through binding to post-synaptic neurons, GABA reduces the neuronal excitability by hyperpolarization. Correct binding between the GABA molecules and its receptors relies on molecular recognition. Earlier studies suggest that recognition is determined by the geometries of the molecule and its receptor. We employed dielectric relaxation spectroscopy (DRS) to study the conformation and dielectric properties of the GABA molecule under physiologically relevant laboratory conditions. The dielectric properties of GABA investigated have given us new insights about the GABA molecule, such as how they interact with each other and with water molecules at different temperatures (22°C and 37.5°C). Higher temperature leads to lower viscosity, thus lower relaxation time. The change in the GABA relaxation time due to concentration change is more associated with the solution viscosity than with the GABA dipole moment. A resonance behavior was observed with high GABA concentrations at physiological temperature, where there might be a phase transition at a certain temperature for a given GABA concentration that leads to a sudden change of the dielectric properties.

In Vitro ACE Inhibitory Activity and Bioactive Compounds of Aqueous Extract of Citrus amblycarpa

Citrus amblycarpa contain flavonoid-rich compounds and play important role in suppressing the conversion of angiotensin-converting enzyme 1 (ACE 1) to angiotensin-enzyme 2 (ACE 2). This study aimed to determine the bioactive compounds in the lime peel extract and their ability as in vitro ACE inhibitor activity. The lime peel extract was obtained by boiling the dried peel and dried leaves for 7 min at 70oC. The bioactive compound of the peel and the leaves were compared. The total phenolic, quercetin, rutin, and GABA were further quantified using spectrophotometer UV vis. The aqueous extract of C. ambylcarpa peel showed a high concentration of phenolic, quercetin, rutin, and GABA than that of the leaves extract. Furthermore, the peel extract at low concentration (0.0001 g/mL) has high efficiency in inhibiting ACE activity up to 133%. It can be concluded that the peel of C. amblycarpa is a good candidate for the management of hypertension.

Enhancement of γ‐aminobutyric acid (GABA) content in fermented milk by using Enterococcus faecium and Weissella confusa isolated from sourdough

In recent years, the development of GABA-enriched foods through exploiting lactic acid bacteria (LAB) has gained much attention. In this study, Enterococcus faecium MDM21 and Weissella confusa MDM8 with high GABA-producing activity were isolated from sourdough and used as single or co-cultures (with Lactococcus lactis subsp. lactis BRM3) in manufacturing fermented milk rich in GABA. The studied strains were non-hemolytic and did not show irregular antibiotic resistance patterns. E. faecium MDM21 exhibited higher acidifying and proteolytic activity and produced higher amounts of GABA in milk than W. confusa MDM8 and Lc. lactis subsp. lactis BRM3, all as single starter cultures. However, higher GABA concentration and lower fermentation time were obtained when they were used as co-cultures with Lc. lactis subsp. lactis BRM3. Overall, the results showed that co-culture of E. faecium MDM21 and Lc. lactis subsp. lactis BRM3 can be introduced as a good candidate to develop novel functional dairy products. Novelty impact statement To the best of our knowledge, this is the first report to identify Weissella confusa as a GABA-producing strain. New fermented milk with high GABA content was produced, whereas no precursor had been used in the formulation. Co-cultures with a potent proteolytic strain enhanced the GABA content significantly in the final product.

Enhancing the production of γ-aminobutyric acid in Escherichia coli BL21 by engineering the enzymes of the regeneration pathway of the coenzyme factor pyridoxal 5’-phosphate

The compound γ-aminobutyric acid (GABA) was widely used in various fields. To enhance the production of GABA in Escherichia coli BL21(DE3), the enzymes of the regeneration pathway of the coenzyme factor pyridoxal 5'-phosphate (PLP) were engineered. The recombinant E. coli strain was screened and identified. The initial concentrations of L-monosodium glutamate (L-MSG) had an obvious influence on the production of GABA. The highest concentration of GABA in recombinant E. coli BL21/pET28a-gadA was 5.54g/L when the initial L-MSG concentration was 10g/L, whereas it was 8.45g/L in recombinant E. coli BL21/pET28a-gadA-SNO1-SNZ1 at an initial L-MSG concentration of 15g/L. The corresponding conversion yields of GABA in these two strains were 91.0% and 92.7%, respectively. When the initial concentrations of L-MSG were more than 15g/L, the concentrations of GABA in E. coli BL21/pET28a-gadA-SNO1-SNZ1 were significantly higher as compared to those in recombinant E. coli BL21/pET28a-gadA, and it reached a maximum of 13.20g/L at an initial L-MSG concentration of 25g/L, demonstrating that the introduction of the enzymes of the regeneration pathway of PLP favored to enhance the production of GABA. This study provides new insight into producing GABA effectively in E. coli BL21(DE3).

Epipregnanolone as a Positive Modulator of GABAA Receptor in Rat Cerebellar and Hippocampus Neurons.

Epipregnanolone (3β-hydroxy-5β-pregnan-20-one, Epi) is an endogenous steroid with important physiological effects and high affinity for GABAA receptors. The effect of Epi on GABA-induced chloride current (IGABA) in native neurons has hardly been studied. In this work, we studied the influence of Epi on the IGABA in the Purkinje cells of rat cerebellum and pyramidal neurons of rat hippocampus with the patch clamp technique. We showed that Epi is a positive modulator of the IGABA with EC50 of 5.7 µM in Purkinje cells and 9.3 µM in hippocampal neurons. Epi-induced potentiation of the IGABA was more potent at low vs. high GABA concentrations. Isopregnanolone (3β-hydroxy-5α-pregnan-20-one, Iso) counteracted Epi, reducing its potentiating effect by 2–2.3 times. Flumazenil, a nonsteroidal GABAA receptor antagonist, does not affect the Epi-induced potentiation. Comparison of the potentiating effects of Epi and allopregnanolone (3α-hydroxy-5α-pregnan-20-one, ALLO) showed that ALLO is, at least, a four times more potent positive modulator than Epi. The combined application of ALLO and Epi showed that the effects of these two steroids are not additive. We conclude that Epi has a dual effect on the IGABA increasing the current in the control solution and decreasing the stimulatory effect of ALLO.

Potential of Lactobacillus strains for health-promotion and flavouring of fermented dairy foods

Ninety-eight Lactobacillus (Lb.) strains were tested for safety traits, health-promoting properties, and sensory characteristics for the strains to be used in the manufacture of fermented dairy products. First, a screening based on the production of biogenic amines was performed, and the potential amine-producing strains were discarded. The remaining 62 strains were analysed for antibiotic resistance, the presence of antibiotic resistance and amino acid decarboxylase genes, and virulence factors (haemolytic, DNAse, and coagulase activity). Principal component analysis of the safety results allowed to select 39 strains. Antimicrobial activity was used to select 13 of them, which were further analysed for sensory characteristics, several interesting enzymatic activities and for γ-aminobutyric acid (GABA), ornithine, and tryptophan production. All these strains produced fermented milks without sensory defects, as well as pleasant sensory properties. Among them, the strains Lb24 and Lb86 highlighted by their β-galactosidase activity; the strain Lb47 was able to hydrolyse bile salts; the strains Lb86 and Lb93 produced high concentrations of both GABA and tryptophan, and the strain Lb111 produced the highest concentrations of ornithine. In consequence, these five strains (Lb24, Lb86, Lb47, Lb93 and Lb111) were selected and could be used in the manufacture of a variety of fermented dairy products.

Molecular cloning and pharmacology of Min-UNC-49B, a GABA receptor from the southern root-knot nematode Meloidogyne incognita.

Root-knot nematodes are plant-parasitic nematodes that cause immense damage to a broad range of cultivated crops by forming root galls, resulting in yield losses in crops. To facilitate the development of faster-acting selective nematicides, we cloned three cDNAs encoding UNC-49B proteins from the southern root-knot nematode Meloidogyne incognita and examined their functional and pharmacological properties by two-electrode voltage clamp electrophysiology using a Xenopus oocyte expression system. The three cloned cDNAs encoded Min-UNC-49B, Min-UNC-49B-L and Min-UNC-49B-XL; the last two proteins have longer N-terminal regions than the first protein. When expressed in Xenopus oocytes, these proteins responded to γ-aminobutyric acid (GABA) to activate currents with high-micromolar or low-millimolar half-maximal effective concentration (EC50 ) values, indicating the formation of functional homo-pentameric GABA receptors. Fipronil and picrotoxinin inhibited GABA-induced currents with high-nanomolar and low-micromolar half-maximal inhibitory concentration (IC50 ) values, respectively, in oocytes expressing Min-UNC-49B. The G2'A and T6'M mutations in the second transmembrane domain of Min-UNC-49B enhanced and reduced the sensitivity of Min-UNC-49B to these two antagonists, respectively. Samaderine B and SF-14 inhibited GABA responses in oocytes expressing Min-UNC-49B with low-micromolar and high-nanomolar IC50 values, respectively. Ivermectin, α-terpineol, thymol and methyl eugenol exerted dual effects on Min-UNC-49B by potentiating currents induced by low concentrations of GABA and inhibiting currents induced by high concentrations of GABA. We have shown that structurally diverse compounds act at Min-UNC-49B GABA receptors. Our results may serve as a starting point to decipher the molecular function of native GABA receptors of plant-parasitic nematodes, which could aid in the structure-based design of novel nematicides. © 2020 Society of Chemical Industry.

GABA, noise and gain in human visual cortex

High levels of GABA (gamma-aminobutyric acid, the brain's primary inhibitory neurotransmitter) are associated with enhanced cognitive and perceptual performance. It has been proposed that these effects result from GABA reducing neural noise or variability, but the precise mechanisms remain unknown. We have measured how individual differences in GABA concentration in the visual cortex are related to performance on a visual contrast discrimination task. Our results reveal that the facilitatory strength of the typical “dipper” function elicited by this task is strongly correlated with GABA concentration. A simple, biologically plausible, network model comprising excitatory and suppressive neural populations accounts for the data well and indicates that the strength of suppression increases as GABA concentration increases. Inter-individual variations in GABA were correlated both with the inhibition strength of the model (mimicking the effect of GABA) and, inversely, with the magnitude of the response criterion. This enhanced suppression has the dual effect of suppressing noise and reducing the gain of the neural response. Our findings thus suggest that the changes in performance conferred by high GABA concentration are mediated by both a reduction of noise and, paradoxically, a reduction in neural, but not perceptual, sensitivity.

Isolation, Identification, and Optimization of γ-Aminobutyric Acid (GABA)-Producing Bacillus cereus Strain KBC from a Commercial Soy Sauce moromi in Submerged-Liquid Fermentation

A new high γ-aminobutyric acid (GABA) producing strain of Bacillus cereus was successfully isolated from soy sauce moromi. This B. cereus strain named KBC shared similar morphological characteristics (Gram-positive, rod-shaped) with the reference B. cereus. 16S rRNA sequence of B. cereus KBC was found to be 99% similar with B. cereus strain OPWW1 under phylogenetic tree analysis. B. cereus KBC cultivated in unoptimized conditions using De Man, Rogosa, Sharpe (MRS) broth was capable of producing 523.74 mg L−1 of GABA within five days of the cultivation period. By using response surface methodology (RSM), pH level, monosodium glutamate (MSG) concentration and temperature were optimized for a high concentration of GABA production. The pH level significantly influenced the GABA production by B. cereus KBC with p-value = 0.0023. GABA production by B. cereus KBC under the optimized condition of pH 7, MSG concentration of 5 g L−1 and temperature of 40 °C resulted in GABA production of 3393.02 mg L−1, which is 6.37-fold higher than under unoptimized conditions. Overall, this study has shown that B. cereus KBC isolated from soy sauce moromi is capable of producing a high concentration of GABA together with the optimal fermentation conditions that have been statistically analysed using RSM.

Use of Streptococcus thermophilus for the in situ production of γ-aminobutyric acid-enriched fermented milk

γ-Aminobutyric acid (GABA) is a potentially bioactive ingredient with health-promoting properties that is added to functional foods. Streptococcus thermophilus was selected to produce naturally GABA-enriched fermented milk. This strain can yield a GABA concentration of 2.8 g/L after a 48-h fermentation. In the presence of 1 g/L food-grade casein hydrolysate as a nitrogen source, S. thermophilus yielded GABA concentrations as high as 5.4 g/L or even 8.3 g/L when cocultured with Lactobacillus rhamnosus. In other words, both of these added conditions promoted GABA enrichment. The GABA dose achieved with fermented milk was comparable to the doses of commercially available GABA supplements. Additionally, the in situ use of S. thermophilus to produce GABA-enriched fermented milk was cost effective. The complete genomic sequence of S. thermophilus GABA has been published and will be highly useful to other researchers studying the regulation of genes related to GABA accumulation. In conclusion, the S. thermophilus GABA-producing strain reported herein represents a natural method for the production of fermented milk containing high GABA concentrations.

Comparative study of striatum GABA concentrations and magnetic resonance spectroscopic imaging in Parkinson's disease monkeys

BackgroundParkinson's disease is a progressive degenerative nervous system disease. Recent studies have shown that secondary changes in the GABA system play directly affect the pathogenesis of PD. There is still much debate about GABA concentrations because currently, GABA concentrations in the brain tissue are obtained indirectly by measuring its concentration in the blood and cerebrospinal fluid. These results are unreliable. Magnetic resonance spectroscopy (MRS) is the only noninvasive method for evaluating the concentration of metabolites in living brain tissue and has been widely applied in research and clinical practice. In addition, combining MEGA-PRESS technology with LCModel software for quantitative GABA measurements is largely recognized. At present, the PD monkeys model in primates has been increasingly proficient. Primates are more similar to humans in terms of brain structure and function than other animals. However, 3.0 T MRS studies involving the PD monkey model to measure metabolites in living subjects with PD are still rare. The study was performed at 3.0 T MRI with control monkeys and PD monkeys that were injected methyl-phenyl-tetrahydropyridine (MPTP) in one side of common carotid artery before and 3 months after successful model establishment to measure GABA concentrations in the bilateral striatum. Behavioral observations were performed for all animals, and the behavioral score was recorded. After 3 months, the GABA concentration in the bilateral striatum was measured in both groups by high-performance liquid chromatography (HPLC). The data obtained from magnetic resonance spectroscopy (MRS) were compared with the actual measured GABA concentrations in tissues isolated from the corresponding regions, and their correlations with the behavior score were analyzed. The research objectives are to investigate the changes of γ-aminobutyric acid (GABA) concentration in the bilateral striatum of monkeys with Parkinson's disease (PD) and the value of quantitatively measuring its concentration by noninvasive 3.0 T spectroscopy.Results(1) The MRS results showed that the GABA concentration in the injured side of the striatum of the PD monkeys was higher than in the contralateral side, but the difference was not statistically significant (P = 0.154). Compared with that the blank control group, the GABA concentration in the striatum of the PD monkeys increased, but there was no difference between the groups (P = 0.381; P = 0.425). (2) The GABA concentration that determined from the isolated specimens by HPLC in the injured side of the striatum of the PD monkeys was significantly higher than that in the contralateral side (P < 0.01). Compared with the blank control group, the PD monkeys had higher GABA concentrations in both sides of the striatum, and there was a significant difference in the lesion side (P = 0.004), while there was a non-significant difference in the contralateral side (P = 0.475). (3) The mean GABA concentration in the injured striatum of PD monkeys determined by MRS was not significantly correlated with the behavioral score (r = 0.146, P = 0.688). The mean GABA concentration in the injured striatum determined from the isolated specimens was positively correlated with the behavioral score in the same period (r = 0.444, P = 0.038).ConclusionThe GABA concentration in the injured striatum of PD monkeys is increased and positively correlated with behavioral changes. Validity of noninvasive 3.0 T MRS to detect PD neurotransmitter changes is limited.

Psychosocial deficits across autism and schizotypal spectra are interactively modulated by excitatory and inhibitory neurotransmission.

Continued human and animal research has strengthened evidence for aberrant excitatory-inhibitory neural processes underlying autism and schizophrenia spectrum disorder psychopathology, particularly psychosocial functioning, in clinical and nonclinical populations. We investigated the extent to which autistic traits and schizotypal dimensions were modulated by the interactive relationship between excitatory glutamate and inhibitory GABA neurotransmitter concentrations in the social processing area of the superior temporal cortex using proton magnetic resonance spectroscopy. In total, 38 non-clinical participants (20 females; age range = 18-35 years, mean (standard deviation) = 23.22 (5.52)) completed the autism spectrum quotient and schizotypal personality questionnaire, and underwent proton magnetic resonance spectroscopy to quantify glutamate and GABA concentrations in the right and left superior temporal cortex. Regression analyses revealed that glutamate and GABA interactively modulated autistic social skills and schizotypal interpersonal features (pcorr < 0.05), such that those with high right superior temporal cortex glutamate but low GABA concentrations exhibited poorer social and interpersonal skills. These findings evidence an excitation-inhibition imbalance that is specific to psychosocial features across the autism and schizophrenia spectra.

In vitro effects of the neuroactive substances serotonin and γ-aminobutyric acid on leucocytes from sticklebacks (Gasterosteus aculeatus)

The majority of parasites have evolved strategies to evade the immune responses of their hosts. Neuroactive substances produced by cestodes are possible candidate molecules for regulating host immune responses. The neurons of helminths can synthesize a wide range of molecules that are identical to the ones functioning in their host organisms, and host lymphocytes have receptors for these neuroactive substances. We hypothesized that in teleost fish, antihelminthic immune responses are regulated via 5-hydroxytryptamine (5-HT, or serotonin) and γ-aminobutyric acid (GABA). In the present study, we investigated the in vitro influence of serotonin, GABA and Schistocephalus solidus (helminth) antigens on basic characteristics of the three-spined stickleback Schistocephalus solidus cellular immune response. Head kidney leucocytes (HKLs) were analysed by flow cytometry for cell viability and the frequency of leucocyte subsets (the granulocyte-to-lymphocyte ratio) and by a chemiluminescence assay for the production of reactive oxygen species (ROS). In short-term (2-h) HKL cultures, 5-HT did not change the total numbers of live HKLs, but the production of ROS decreased significantly with all 5-HT concentrations. In long-term (96-h) cultures, high 5-HT concentrations induced a decrease in leucocyte viability. This coincided with elevated ROS production in cultures with all 5-HT concentrations. In short-term (2-h) HKL cultures, GABA did not change the total numbers of live HKLs, but the production of ROS decreased significantly with high (100 nmol L−1) GABA concentrations. In long-term (96-h) cultures, high and medium concentrations of GABA (100 nmol L−1 and 10 nmol L−1) elevated the numbers of live HKLs compared to controls. The granulocyte-to-lymphocyte ratios generally increased upon exposure to GABA at all concentrations. All concentrations of GABA alone elevated the ROS production of HKLs compared to controls. In the present work, we showed that the neuroactive substances serotonin and GABA regulate the teleost immune system. Our study supports the hypothesis that these substances might be immunomodulators in tapeworm–fish parasite-host interactions.

Effects of Non-Protein Amino Acids in Nectar on Bee Survival and Behavior.

Nectar mediates complex interactions between plants and animals. Recent research has focused on nectar secondary compounds that may play a role in regulating some of these interactions. These compounds may affect the behavior of nectar feeders by interacting with their neurobiology. Non-protein amino acids (NPAAs) can constitute a large portion of the amino acid content of floral nectar, but their ecological function has, to date, not been investigated. In this study, we tested the effects of diets with low and high concentrations of γ-amino butyric acid (GABA) and β-alanine on the survival and behavior of Bombus terrestris and Apis mellifera. The most apparent effect on longevity was observed for B. terrestris workers that fed on high concentration of GABA, with longevity increased. By contrast, neither of the two NPAAs (at either concentration) had an affect on A. mellifera longevity. At the low NPAA concentration, only B. terrestris workers showed a difference in consumption, consuming more β-alanine solution than the other two solutions. By contrast, at the high NPAA concentration, only A. mellifera workers showed a difference in consumption, consuming more β-alanine solution. The effects of the NPAAs on behavior differed between the two species, with B. terrestris appearing more sensitive to the NPAAs than A. mellifera. After consuming NPAAs, B. terrestris showed changes in three (walking, flying, stationary) of the four behaviors recorded, although the effects varied with concentration and compound. In contrast, honey bees only showed a change in feeding behavior, with consumption of both NPAAs (at low concentrations) resulting in a decrease. Thus, pollinator intake of NPAAs may have important behavioral/ecological implications.

Analysis of the protective effects of γ-aminobutyric acid during fluoride-induced hypothyroidism in male Kunming mice

Context: Compounds to treat hypothyroidism in the absence of cardiac side effects are urgently required. In this regard, γ-aminobutyric acid (GABA) has gained interest due to its anti-anxiolytic, antihypertensive and antioxidant properties, and reported benefits to the thyroid system.Objective: We investigated the ability of GABA to ameliorate fluoride-induced thyroid injury in mice, and investigated the mechanism(s) associated with GABA-induced protection.Materials and methods: Adult male Kumning mice (N = 90) were exposed to NaF (50 mg/kg) for 30 days as a model of hypothyroidism. To evaluate the effects of GABA administration, fluoride-exposed mice received either thyroid tablets, or low (25 mg/kg), medium (50 mg/kg) or high (75 mg/kg) concentrations of pure GABA orally for 14 days groups (N = 10 each). The effects of low (50 mg/kg); medium (75 mg/kg) and high (100 mg/kg) concentrations of laboratory-separated GABA were assessed for comparison. Effects on thyroid hormone production, oxidative stress, thyroid function-associated genes, and side-effects during therapy were measured.Results: GABA supplementation in fluoride-exposed mice significantly increased the expression of thyroid TG, TPO, and NIS (P < 0.05), significantly improved the thyroid redox state (P < 0.05), modulated the expression of thyroid function-associated genes, conferred liver metabolic protection, and prevented changes to myocardial morphology, thus reducing side effects. Both pure and laboratory-separated GABA displayed comparative protective effects.Discussion and conclusion: Our findings support the assertion that GABA exerts therapeutic potential in hypothyroidism. The design and use of human GABA trials to improve therapeutic outcomes in hypothyroidism are now warranted.

The dynamics of cortical GABA in human motor learning.

Key points The ability to learn new motor skills is supported by plasticity in the structural and functional organisation of the primary motor cortex in the human brain.Changes inhibitory to signalling by GABA are thought to be crucial in inducing motor cortex plasticity.This study used magnetic resonance spectroscopy (MRS) to quantify the concentration of GABA in human motor cortex during a period of motor learning, as well as during a period of movement and a period at rest.We report evidence for a reduction in the MRS‐measured concentration of GABA specific to learning. Further, the GABA concentration early in the learning task was strongly correlated with the magnitude of subsequent learning: higher GABA concentrations were associated with poorer learning.The results provide initial insight into the neurochemical correlates of cortical plasticity associated with motor learning, specifically relevant in therapeutic efforts to induce cortical plasticity during recovery from stroke. The ability to learn novel motor skills is a central part of our daily lives and can provide a model for rehabilitation after a stroke. However, there are still fundamental gaps in our understanding of the physiological mechanisms that underpin human motor plasticity. The acquisition of new motor skills is dependent on changes in local circuitry within the primary motor cortex (M1). This reorganisation has been hypothesised to be facilitated by a decrease in local inhibition via modulation of the neurotransmitter GABA, but this link has not been conclusively demonstrated in humans. Here, we used 7 T magnetic resonance spectroscopy to investigate the dynamics of GABA concentrations in human M1 during the learning of an explicit, serial reaction time task. We observed a significant reduction in GABA concentration during motor learning that was not seen in an equivalent motor task lacking a learnable sequence, nor during a passive resting task of the same duration. No change in glutamate was observed in any group. Furthermore, M1 GABA measured early in task performance was strongly correlated with the degree of subsequent learning, such that greater inhibition was associated with poorer subsequent learning. This result suggests that higher levels of cortical inhibition may present a barrier that must be surmounted in order to achieve an increase in M1 excitability, and hence encoding of a new motor skill. These results provide strong support for the mechanistic role of GABAergic inhibition in motor plasticity, raising questions regarding the link between population variability in motor learning and GABA metabolism in the brain.