Gamma-aminobutyric Acid Research Articles

Exosomal therapy mitigates silver nanoparticles-induced neurotoxicity in rats

Introduction Our investigation aims to appraise the neuroprotective impact of Bone Marrow-Mesenchymal Stem Cells (BM-MSCs) derived exosomes against Ag NPs-inducing neurotoxicity in rats. Materials and Methods Twenty-four albino rats were divided into 3 groups. Group I (control negative), Group II (intraperitoneally injected with Ag NPs for 28 days, whereas Group III (intraperitoneally injected with Ag NP and BM-MSCs derived exosomes. Results There was a marked elevation of Malondialdehyde (MDA) along with a reduction of brain antioxidants, Gamma-aminobutyric acid (GABA) and Monoamine Oxidase (MAO) in the Ag NPs receiving group. Ag NPs upregulated c-Jun N-terminal Kinases (JNK) genes and c-Myc and downregulated the tissue inhibitors of metalloproteinases (TIMP-1) and Histone deacetylase 1 (HDAC1) genes. Otherwise, the co-treatment of BM-MSCs derived exosomes with Ag NPs could markedly increase the rat’s body weight, activity and learning while, decreasing anxiety, restoring all the toxicological parameters and improving the microscopic appearance of different brain areas. Conclusion BM-MSCs-derived exosomes downregulated both apoptotic and inflammatory mediators and upregulated the antiapoptotic genes. BM-MSCs-derived exosomes exhibit a great therapeutic effect against the neurotoxic effects of Ag NPs.

Lacticaseibacillus paracasei 207-27 alters the microbiota-gut-brain axis to improve wearable device-measured sleep duration in healthy adults: a randomized, double-blind, placebo-controlled trial.

Objective: Probiotics have been reported to exert beneficial effects on sleep through the gut-brain axis. Therefore, this randomized, double-blind, placebo-controlled trial assessed the effects of Lacticaseibacillus paracasei 207-27 supplementation on sleep quality and its safety and potential mechanisms. Method and study design: Healthy adults under mild stress aged 18-35 years consumed low or high doses of L. paracasei 207-27 or a placebo for 28 days. Fecal samples, blood samples, and questionnaires were collected at the baseline and the end of the intervention. Sleep quality was measured using wearable devices and Pittsburgh sleep quality index (PSQI) questionnaire. Serum inflammatory markers, corticotropin-releasing hormone, adrenocorticotropic hormone (ACTH), cortisol (COR), γ-aminobutyric acid, and 5-hydroxytryptamine levels were detected using enzyme-linked immunosorbent assay. The gut microbiota was analyzed using 16S rRNA sequencing and bioinformatics. Short-chain fatty acids levels were detected using gas chromatography-mass spectrometry. Results: Both the low-dose and high-dose groups exhibited significant improvements in wearable device- measured sleep duration compared to the placebo group. The global scores of PSQI in three groups significantly decreased after intervention without statistical difference between groups. At the phylum level, the low-dose group exhibited a higher relative abundance of Bacteroidota and a lower Firmicutes-to-Bacteroidetes (F/B) ratio. At the genus level, two treatment groups had higher relative abundance of Bacteroides and Megamonas, alongside lower levels of Escherichia-Shigella. Furthermore, the low-dose group exhibited significant increases in acetic acid, propionic acid, butyric acid, and valeric acid levels, while two treatment groups exhibited a significant decrease in COR levels. Correlation analysis revealed that the increased levels of acetic acid and butyric acid in the low-dose group may be associated with decreased ACTH. Conclusion: L. paracasei 207-27 administration in healthy adults resulted in improvements in gut microbiota community and sleep duration. The mechanisms might involve modulation of the gut microbiota structure to regulate the function of the gut-brain axis, including increases in SCFA levels and decreases in hypothalamic-pituitary-adrenal axis activity. The Chinese clinical trial registry number is ChiCTR2300069453 (https://www.chictr.org.cn/showproj.html?proj=191193, registered 16 May 2023 - retrospectively registered).

Disrupting stroke-induced GAT-1-syntaxin1A interaction promotes functional recovery after stroke.

Although stroke is a frequent cause of permanent disability, our ability to promote stroke recovery is limited. Here, we design a small-molecule stroke recovery promoting agent that works by dissociating γ-aminobutyric acid (GABA) transporter 1 (GAT-1) from syntaxin1A (Synt1A), a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein. Stroke induces an increase in GAT-1-Synt1A interaction in the subacute phase, a critical period for functional recovery. Uncoupling GAT-1-Synt1A reverses stroke-induced GAT-1 dysfunction and cortical excitability decline and enhances synaptic GABAergic inhibition and consequently cortical oscillations and network plasticity by facilitating the assembly of the SNARE complex at the synapse. Based on the molecular mechanism of GAT-1 binding to Synt1A, we design GAT-1-Synt1A blockers. Among them, ZLQ-3 exhibits the greatest potency. Intranasal use of ZLQ-3-1, a glycosylation product of ZLQ-3, substantially lessens impairments of sensorimotor and cognitive functions in rodent models. This compound, or its analogs, may serve as a promoting agent for stroke recovery.

Characterizing and optimizing glutamate decarboxylase from Priestia flexa for efficient biosynthesis of γ-aminobutyric acid from l-glutamic acid powder

Gamma-aminobutyric acid (GABA) is widely applied in the food and pharmaceutical industries, and is experiencing a continually growing market demand. Nevertheless, the efficient and stable production of GABA confronts challenges, especially the instability of its core enzyme, glutamate decarboxylase (GAD). GAD exhibits high activity under acidic conditions but very poor stability. This limitation severely restricts its application in large-scale industrial production. In this study, we identified and characterized a GAD from Priestia flexa (PfGAD) with high activity. We further developed a variant with significantly enhanced acidic st ability. The specific activity of the variant achieved 139.8 U/mg, and its residual activity remained approximately 90 % after overnight incubation in pH 3.0 buffer. Moreover, we engineered a strain by overexpressing a transporter protein for GABA and l-glutamic acid, while deleting the pepD gene. The yield of GABA led to 251.8 g L−1, accompanied by a conversation rate of 97.8 %, meanwhile the cell growth maintained normal. Our approach successfully addresses the challenge of balancing cell growth and GABA accumulation. Our findings offer valuable insights into acid resistance modification of the enzyme, and optimizing GABA production through strain modification, holding significant potential for the industrial application of GABA.

Identification of metabolomic changes and potential therapeutic targets during ovarian aging.

To reveal the metabolic differences of follicle fluid (FF) and granulosa cell (GC) between younger women and advanced age women in ART cycles, and then find potential therapeutic targets of ovarian aging. Forty-five patients were included in the study and they were divided into three groups according to their age (Group A: 20-30 years old; Group B: 30-35 years old; Group C: 35-45 years old). All patients underwent controlled ovarian stimulation using the follicular phase long-acting protocol, FF and GC were obtained 36-38 hours after HCG administration. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for metabolomics analysis and metabolic pathway analysis (MetPA) was utilized to find related pathways. Between group A and group C, there were 72 and 21 differential metabolites in FF and GC, respectively. KEGG enrichment analysis showed six pathways were co-enriched by the differential metabolites of FF and GC. Among them, we noticed that in the pathway GABAergic synapse, GABA (gamma-aminobutyric acid) was down-regulated in GC, while its downstream metabolite succinic acid was down-regulated in FF. Further ROC curve analysis was performed on these two metabolites, and the results showed that they all had a favorable predictive value. This study indicated that GABA and succinic acid could be potential therapeutic targets for ovarian aging, GABA may delay ovarian aging and improve ovarian function through its antioxidant properties, which may be a future direction of clinical treatment.

Light-Activated Agonist-Potentiator of GABAA Receptors for Reversible Neuroinhibition in Wildtype Mice.

Gamma aminobutyric acid type A receptors (GABAARs) play a key role in the mammalian central nervous system (CNS) as drivers of neuroinhibitory circuits, which are commonly targeted for therapeutic purposes with potentiator drugs. However, due to their widespread expression and strong inhibitory action, systemic pharmaceutical potentiation of GABAARs inevitably causes adverse effects regardless of the drug selectivity. Therefore, therapeutic guidelines must often limit or exclude clinically available GABAAR potentiators, despite their high efficacy, good biodistribution, and favorable molecular properties. One solution to this problem is to use drugs with light-dependent activity (photopharmacology) in combination with on-demand, localized illumination. However, a suitable light-activated potentiator of GABAARs has been elusive so far for use in wildtype mammals. We have met this need by developing azocarnil, a diffusible GABAergic agonist-potentiator based on the anxiolytic drug abecarnil that is inactive in the dark and activated by visible violet light. Azocarnil can be rapidly deactivated with green light and by thermal relaxation in the dark. We demonstrate that it selectively inhibits neuronal currents in hippocampal neurons in vitro and in the dorsal horns of the spinal cord of mice, decreasing the mechanical sensitivity as a function of illumination without displaying systemic adverse effects. Azocarnil expands the in vivo photopharmacological toolkit with a novel chemical scaffold and achieves a milestone toward future phototherapeutic applications to safely treat muscle spasms, pain, anxiety, sleep disorders, and epilepsy.

Altered functional connectivity within the primary visual networks and neurotransmitter activity in male smokers: A group ICA study

Smoking puts patients at high risk for cognitive and psychiatric disorders. The aim of this study was to explore the effects of nicotine use on primary visual network (PVN) and its association with neurotransmitters. A total of 59 tobacco use disorder (TUD) patients and 51 healthy controls (HC) participated in this study and underwent resting state functional magnetic resonance imaging scans. Functional connectivity (FC) within the network was explored using independent component analysis. In addition, the spatial correlations of PVN changes with neurotransmitters and their correlations with clinical characteristics of patients were evaluated using the JuSpace toolbox and SPSS. We found reduced FC within the PVN in patients with TUD compared with HC. In terms of relevant analysis, there is a spatial correlation between FC changes in the patient's PVN and a higher distribution of dopamine receptor and gamma-aminobutyric acid receptor. This study revealed changes in the FC and neurotransmitters of the PVN in patients with TUD, expanding the potential neural mechanisms underlying sensory perception and psychiatric disorders.

Evaluation of the sedative-motor effects of novel GABAkine imidazodiazepines using quantitative observation techniques in rhesus monkeys.

Benzodiazepines bind to γ-aminobutyric acid type A (GABAA) receptor subtypes identified by different α subunits (i.e., α1GABAA, α2GABAA, α3GABAA, and α5GABAA). Sedative-motor effects of benzodiazepines are thought to involve α1GABAA and α3GABAA subtypes. We evaluated observable measures of sedative-motor effects and species-typical behaviors in monkeys following acute administration of novel GABAkines (positive allosteric modulators of GABAA receptors), with varying degrees of selective efficacy at different GABAA receptor subtypes. We predicted that the induction of sedative-motor effects would depend on the degree of α1GABAA and α3GABAA efficacy. Adult female rhesus monkeys (N = 4) were implanted with chronic indwelling i.v. catheters. Quantitative behavioral observation was conducted by trained observers following administration of multiple doses of the conventional benzodiazepine alprazolam and the GABAkines MP-III-80 (preferential efficacy at α2/α3/α5GABAA subtypes), KRM-II-81, MP-III-24 (both with preferential efficacy for α2/α3GABAA subtypes), and MP-III-22 (preferential potency and efficacy for α5GABAA subtypes). As with alprazolam, all GABAkines induced significant levels of mild sedation ("rest/sleep posture"). Deep sedation was observed with alprazolam, MP-III-80, and MP-III-22; motoric effects (observable ataxia) were obtained with alprazolam, KRM-II-81, and MP-III-22 only. Surprisingly, the order of potency for rest/sleep posture was significantly associated only with potency at α5GABAA subtypes. GABAkines with preferential efficacy at α2/α3GABAA and/or α5GABAA subtypes engendered sedative-motor effects in monkeys, although only compounds with α5GABAA activity engendered deep sedation. Moreover, the significant relationship between potency obtained with in vitro electrophysiology data and the rest/sleep posture measure suggests a role for the α5GABAA subtype in this milder form of sedation.

Palatability of organic acids and their derivatives for cichlid fishes (Cichlidae)

Taste attractivity of 15 organic acids and their derivatives (ascorbic, citric, sorbic, malic, oxalic, acetic, glycolic, α- and γ-aminobutyric acids, their Na+- and K+-salts; 0,1 M) was compared for 5 species of cichlid fishes (Cichlidae) – Nile Oreochromis niloticus and Mozambique O. mossambicus tilapias, golden mbuna Melanochromis auratus, lemon cichlid Neolamprologus leleupi and tailbar cichlid Vieja hartwegi. Citric and oxalic acids, Na+-ascorbate, K+-sorbate and K+-citrate, ammonium oxalate have an attractive or indifferent taste for fish, ascorbic and sorbic acids, Na+-citrate and Na+-malate have an aversive or indifferent taste. Malic acid has an attractive taste for tailbar cichlid, an aversive taste for Mozambique tilapia and an indifferent taste for other cichlids. Acetic acid and isomers of aminobutyric acid have indifferent taste for all fishes. The taste attractivity of organic acids may be different compared to salts formed on their basis. The attractiveness of salts is higher than that of the corresponding acids in 10 out of 28 cases, lower in 4 cases, and the same in 14 cases. The conversion of ascorbic and sorbic acids into Na+ and K+ salts is accompanied by an increase in taste attractivity in most cichlids, malic acid to malate Na+ – in half of the species. For most fish, citric acid and its Na+- and K+-salts have similar attractiveness. Oxalic acid, compared with ammonium oxalate, has a higher attractiveness for lemon cichlid, a lower one for Mozambique tilapia and the same taste quality for the other three fish species. There are no differences between the consumption of agar pellets with isomers of aminobutyric acid and pellets with acetic and glycolic (hydroxy acetic) acids in all cichlids. The feeding behavior shown by cichlids during the orosensory testing of pellets is similar – fish perform a small number of rejections and repeated grasps of pellets, the duration of pellet retention time in the oral cavity is similar.

Senegenin regulates the mechanism of insomnia through the Keap1/Nrf2/PINK1/Parkin pathway mediated by GAD67.

GAD67 impacts insomnia as a key enzyme catalysing the conversion of glutamate (Glu) to gamma-aminobutyric acid (GABA). Senegenin enhances neuroprotection and is used widely to treat insomnia and other neurological diseases. This study aimed to investigate how senegenin regulates insomnia through a GAD67-mediated signalling pathway. We measured GAD67 expression levels in insomnia patients and evaluated the expression levels of GAD67 and Keap1/Nrf2/Parkin/PINK1-related cytokines following GAD67 lentiviral transfection in PC12 cells and in rat models. We also assessed cellular reactive oxygen species (ROS) and mitochondrial membrane potential levels. Additionally, EEG/EMG was used to analyse the sleep phases of rats and to assess memory and exploration functions. Pathological changes and the expression of GAD67 and sleep-related proteins in the hippocampus were examined. The results showed that GAD67 expression was increased in insomnia patients, ROS levels were elevated, and the mitochondrial membrane potential was decreased in the GAD67-KD group. Insomnia rats exhibited changes in sleep rhythm, learning, and exploration dysfunction, pathological changes in the CA1 region of the hippocampus, and differential expression of GAD67 and sleep-related factors. Inhibitory neurofactor expression levels were decreased in insomnia rats, showing a positive correlation in the GAD67-KD group and a negative correlation in the GAD67-OE group. Conversely, excitatory factor expression levels were increased in insomnia rats, showing a positive correlation in the GAD67-KD group and a negative correlation in the GAD67-OE group. Senegenin intervention modulated cytokine expression levels. In conclusion, GAD67 negatively regulates insomnia, and senegenin can regulate insomnia by mediating the expression of cytokines in the GAD67-regulated Keap1/Nrf2/Parkin/PINK1 pathway.

Adaptive laboratory evolution of Lipomyces starkeyi for high production of lignin derivative alcohol and lipids with comparative untargeted metabolomics-based analysis.

Adaptive laboratory evolution (ALE) is an impactful technique for cultivating microorganisms to adapt to specific environmental circumstances or substrates through iterative growth and selection. This study utilized an adaptive laboratory evolution method on Lipomyces starkeyi for high tolerance in producing lignin derivative alcohols and lipids from syringaldehyde. Afterward, untargeted metabolomics analysis was employed to find the key metabolites that play important roles in the better performance of evolved strains compared to the wild type. Lignin, a prominent constituent of plant biomass, is a favorable source material for the manufacture of biofuel and lipids. Nevertheless, the effective transformation of chemicals produced from lignin into products with high economic worth continues to be a difficult task. In this study, we exposed L. starkeyi to a series of flask passaging experiments while applying selective pressure to facilitate its adaptation to syringaldehyde, a specific type of lignin monomeric aldehyde. Using ALE, we successfully developed a new strain, DALE-22, which can synthesize syringyl alcohol up to 18.74 mM from 22.28 mM syringaldehyde with 41.9% lipid accumulation. In addition, a comprehensive examination of untargeted metabolomics identified six specific crucial metabolites linked to the improved tolerance of the evolved strain in the utilization of syringaldehyde, including 2-aminobutyric acid, allantoin, 4-hydroxyphenethyl alcohol, 2-aminoethanol, tryptophan, and 5-aminovaleric acid. The results of our study reveal how L. starkeyi adapts to using substrates produced from lignin. These findings offer important information for developing strategies to improve the process of converting lignin into valuable products for sustainable biorefinery applications.

Relationship between the GABA Pathway and Signaling of Other Regulatory Molecules

GABA (gamma-aminobutyric acid) is an amino acid whose numerous regulatory functions have been identified in animal organisms. More and more research indicate that in plants, this molecule is also involved in controlling basic growth and development processes. As recent studies have shown, GABA plays an essential role in triggering plant resistance to unfavorable environmental factors, which is particularly important in the era of changing climate. The main sources of GABA in plant cells are glutamic acid, converted in the GABA shunt pathway, and polyamines subjected to oxidative degradation. The action of GABA is often related to the activity of other messengers, including phytohormones, polyamines, NO, H2O2, or melatonin. GABA can function as an upstream or downstream element in the signaling pathways of other regulators, acting synergistically or antagonistically with them to control cellular processes. Understanding the role of GABA and its interactions with other signaling molecules may be important for developing crop varieties with characteristics that enable adaptation to a changing environment.

Gamma-Aminobutyric Acid (GABA) as a Defense Booster for Wheat against Leaf Rust Pathogen (Puccinia triticina).

Wheat leaf rust, caused by Puccinia triticina, poses a growing threat to global wheat production, necessitating alternative strategies for effective disease management. This study investigated the potential of gamma-aminobutyric acid (GABA) to enhance resistance to leaf rust in two wheat cultivars: the susceptible Morocco and moderately resistant Sakha 94 cultivar. Our findings revealed that GABA significantly improved resistance in both cultivars to P. triticina, particularly in Morocco, by mitigating disease severity and reducing pustule density and size while extending both incubation and latent periods. This study assessed the effectiveness of two GABA application methods: plants received 1 mM GABA treatment, as a foliar spray, twenty-four hours prior to infection (pre-GABA), and plants received 1 mM GABA treatment both 24 h before and after infection (pre-/post-GABA), with the latter yielding significantly better results in reducing infection severity and improving plant resilience. Additionally, GABA application influenced stomatal behavior, promoting closure that may enhance resilience against leaf rust. GABA application on plants also modulated the production of reactive oxygen species (ROS). This led to a stronger oxidative burst in both susceptible and moderately resistant cultivars. GABA increased O2●- levels in guard cells and surrounding stomata, enhancing stomatal closure and the hypersensitive response. GABA enhanced the accumulation of soluble phenols and increased the activity of key antioxidant enzymes, catalase (CAT) and peroxidase (POX), which are vital for managing oxidative stress. To the best of our knowledge, this investigation represents the first report into the impact of GABA on wheat leaf rust disease.

Regulation of Glutamate and γ-Aminobutyric Acid Receptors in Rats with Depression by Sniffing the Essential Oil of Citrus × aurantium L. [Rutaceae

Background Modern research has proved that the volatile oil (VO) of Citrus × aurantium L. [Rutaceae] has the effect of treating depression, but the mechanism of treating depression by sniffing has not been studied. Purpose To study the mechanism of VO on depression. Methods Part I: Except for the blank group, the sniffing group and nasal drip group were continuously administered for 7 days to investigate the optimal administration method. Part II: Except for the blank group, the model, positive group, high, medium, and low dose group of VO were established by chronic unpredictable stress test. The VO was given on the 7th day of modeling for 17 consecutive days. The expression of neurotransmitters and receptors in the brain was determined. The medicinal ingredients in rat brain tissue and blood were detected by gas chromatography–mass spectrometry (GC–MS). Results Compared with nasal drip, sniffing administration has less irritation to the nasal mucosa. The VO could reduce the forced swimming immobility time, adjust the activity state, increase the content of γ-aminobutyric acid (GABA), reduce the content of glutamate, and upregulate the expression of GABAα1, GABAγ2, and their mRNA. The main pharmaceutical component is d-limonene. Conclusion d-limonene in VO upregulates GABAα1, GABAγ2 expression to treat depression.

Comprehensive stable-isotope tracing of glucose and amino acids identifies metabolic by-products and their sources in CHO cell culture

Mammalian cell culture processes are widely utilized for biotherapeutics production, disease diagnostics, and biosensors, and hence, should be optimized to support robust cell growth and viability. However, toxic by-products accumulate in cultures due to inefficiencies in metabolic activities and nutrient utilization. In this study, we applied comprehensive 13C stable-isotope tracing of amino acids and glucose to two Immunoglobulin G (IgG) producing Chinese Hamster Ovary (CHO) cell lines to identify secreted by-products and trace their origins. CHO cells were cultured in media formulations missing a single amino acid or glucose supplemented with a 13C-tracer of the missing substrate, followed by gas chromatography-mass spectrometry (GC-MS) analysis to track labeled carbon flows and identify by-products. We tracked the sources of all secreted by-products and verified the identity of 45 by-products, majority of which were derived from glucose, leucine, isoleucine, valine, tyrosine, tryptophan, methionine, and phenylalanine. In addition to by-products identified previously, we identified several metabolites including 2-hydroxyisovaleric acid, 2-aminobutyric acid, L-alloisoleucine, ketoisoleucine, 2-hydroxy-3-methylvaleric acid, desmeninol, and 2-aminobutyric acid. When added to CHO cell cultures at different concentrations, certain metabolites inhibited cell growth while others including 2-hydroxy acids, surprisingly, reduced lactate accumulation. In vitro enzymatic analysis indicated that 2-hydroxy acids were metabolized by lactate dehydrogenase suggesting a possible mechanism for lowered lactate accumulation, e.g., competitive substrate inhibition. The 13C-labeling assisted metabolomics pipeline developed and the metabolites identified will serve as a springboard to reduce undesirable by-products accumulation and alleviate inefficient substrate utilization in mammalian cultures used for biomanufacturing and other applications through altered media formulations and pathway engineering strategies.

GABALAGEN Facilitates Pentobarbital-Induced Sleep by Modulating the Serotonergic System in Rats.

Gamma-aminobutyric acid (GABA) is one of the inhibitory neurotransmitters with beneficial effects including sedative properties. However, despite various clinical trials, scientific evidence regarding the impact on sleep of orally ingested GABA, whether natural or synthesized through biological pathways, is not clear. GABALAGEN (GBL) is the product of fermented collagen by Lactobacillus brevis BJ20 (L. brevis BJ20) and Lactobacillus plantarum BJ21 (L. plantarum BJ21), enriched with GABA and characterized by low molecular weight. The aim of this study was to investigate the effect of GBL on sleep improvement via a receptor binding assay in a pentobarbital-induced sleep-related rat model. We utilized a pentobarbital-induced sleep-related rat model to conduct this research. The present study investigated the sedative effects of GBL through electroencephalography (EEG) analysis in the pentobarbital-induced sleep animal model. Exploration of the neural basis of these positive effects involved evaluating orexin in the brain via immunohistochemical methods and 5-HT in the serum using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we conducted a binding assay for 5-HT2C receptors, as these are considered pivotal targets in the mechanism of action for sleep aids. Diazepam (DZP) was used as a positive control to compare the efficacy of GBL. Results: In the binding assay, GBL displayed binding affinity to the 5-HT2C receptor (IC50 value, 5.911 µg/mL). Administration of a low dose of GBL (GBL_L; 100 mg/kg) increased non-rapid eye movement sleep time and decreased wake time based on EEG data in pentobarbital-induced rats. Administration of a high dose of GBL (GBL_H; 250 mg/kg) increased non-rapid eye movement sleep time. Additionally, GBL groups significantly increased concentration of the 5-HT level in the serum. GBL_H decreased orexin expression in the lateral hypothalamus. Conclusion: Overall, the sedative effect of GBL may be linked to the activation of serotonergic systems, as indicated by the heightened affinity of the 5-HT2C receptor binding and elevated levels of 5-HT observed in the serum. This suggests that GBL holds promise as a novel compound for inducing sleep in natural products.

Regulation of eating quality, sensory aroma and 2-acetyl-1-pyrroline biosynthesis in fragrant rice through foliage application of aromatic compounds

The experiment was conducted at the research area of Sher-e-Bangla Agricultural University from 15 June 2022, to 25 November 2022 (Aman season) to evaluate the impact of aromatic compound application on fragrant rice. The experiment included two factors: factor 1 comprised four rice varieties (BRRI dhan34, BRRI dhan70, BRRI dhan80, and Tulshimala), and factor 2 comprised application of four aromatic compounds (L-proline, α-ketoglutaric acid, γ-aminobutyric acid, and sodium selenite). A randomized complete block design was employed with three replications. Results revealed significant effects of aromatic compound applications and/or rice varieties on grain eating qualities, sensory aroma and 2-acetyl-1-pyrroline, which were superior in Tulshimala and BRRI dhan34. α-Ketoglutaric acid and sodium selenite application improved water uptake ratio, amylose and amylopectin content, alkali spreading value, gel consistency, protein content, sensory aroma score, and kernel stickiness and tenderness of fragrant rice. Moreover, α-ketoglutaric acid application led to enhanced 2-acetyl-1-pyrroline content in Tulshimala and BRRI dhan34. Several eating quality and fragrance parameters were found either positively or negatively correlated. Apparent amylose content exhibited a negative correlation with stickiness of kernel. Sensory aroma and grain 2-AP content were also positively correlated.

Enhancement of γ-aminobutyric acid content in Huangjiu through rice bran fermentation and its impact on the volatile organic compounds

Rice bran has high glutamic acid decarboxylase (GAD) activity and can be used to enrich and produce γ-aminobutyric acid (GABA). Glutinous rice was used as raw material to brew Huangjiu by liquefaction fermentation. Rice bran extract was added at different fermentation stages, then the content of GABA and basic physicochemical properties were tested, the changes of flavor substances and volatile organic compounds (VOCs) were observed in Huangjiu. The results showed the addition of concentrated GABA-enriched rice bran extract during the post-fermentation stage significantly increases the GABA content in Huangjiu. When the amount of rice bran used is 50 g, the GABA content in the Huangjiu can reach 592.44 mg/L after fermentation. The total sugar and pH of Huangjiu fermented with rice bran extract were higher than the control group, and the total acid and non-sugar solids were lower than the control group. Electronic tongue analysis showed that the addition of rice bran extract would affect the sourness, umami and saltiness taste of Huangjiu. Gas Chromatography-Ion Mobility Spectrometry (GC-IMS) analysis of Huangjiu made by adding rice bran extract at the post-fermentation stage showed increased isoamyl acetate, 2-heptanol, and other substances in comparison with the control group. The results of the study provide a cost-effective and rapid method for increasing the GABA content in Huangjiu. It also offers a theoretical basis and scientific guidance for the production of health-oriented Huangjiu.

Comparative Analysis of Microbial Diversity and Metabolic Profiles during the Spontaneous Fermentation of Jerusalem Artichoke (Helianthus tuberosus L.) Juice.

Jerusalem artichoke juice is valued for its nutritional content and health benefits. Spontaneous fermentation enhances its flavor, quality, and functional components through microbial metabolic activities. This study used high-throughput sequencing to analyze microbial community changes, and LC-MS and GC-MS to detect secondary metabolites and flavor compounds during fermentation. During natural fermentation, beneficial bacteria like Lactobacillus and Pediococcus increased, promoting lactic acid production and inhibiting harmful bacteria, while environmental bacteria decreased. Similarly, fungi shifted from environmental types like Geosmithia and Alternaria to fermentation-associated Pichia and Penicillium. A total of 1666 secondary metabolites were identified, with 595 upregulated and 497 downregulated. Key metabolic pathways included phenylpropanoid biosynthesis, with significant increases in phenylalanine, tryptophan, and related metabolites. Lipid and nucleotide metabolism also showed significant changes. Flavor compounds, including 134 identified alcohols, esters, acids, and ketones, mostly increased in content after fermentation. Notable increases were seen in Phenylethyl Alcohol, Ethyl Benzenepropanoate, 3-Methylbutyl Butanoate, Ethyl 4-Methylpentanoate, 5-Ethyl-3-Hydroxy-4-Methyl-2(5H)-Furanone, Ethyl Decanoate, Hexanoic Acid, and 1-Octanol. γ-aminobutyric acid (GABA) and other functional components enhanced the health value of the juice. This study provides insights into microbial and metabolic changes during fermentation, aiding in optimizing processes and improving the quality of fermented Jerusalem artichoke juice for functional food development.

Comparative Electroencephalographic Profile of a New Anesthetic and Anticonvulsant That Is Selective for the GABAAR Slow Receptor Subtype

BACKGROUND: Anesthetics like propofol increase electroencephalography (EEG) power in delta frequencies (0.1–4 Hz), with a decrease of power in bandwidths >30 Hz. Propofol is nonselective for gamma amino butyric acid type A receptor subtypes (GABAAR) as it enhances all 3 GABAAR subtypes (slow, fast, and tonic). Our newly developed anesthetic class selectively targets GABAAR-slow synapses to depress brain responsiveness. We hypothesized that a selective GABAAR-slow agonist, KSEB 01-S2, would produce a different EEG signature compared to the broad-spectrum GABAAR agonist (propofol), and tested this using rat EEG recordings. METHODS: Male rats were studied after Institutional Animal Care and Use Committees (IACUC) approval from the US Army Medical Research Institute of Chemical Defense and the University of Michigan. Rats were anesthetized using isoflurane (3%–5% induction, 1%–3% maintenance) with oxygen at 0.5 to 1.0 L/min. Stainless steel screws were placed in the skull and used to record subcranial cortical EEG signals. After recovery, either propofol or KSEB 01-S2 was administered and effects on EEG signals were analyzed. RESULTS: As previously reported, propofol produced increased power in delta frequencies (0.1–4 Hz) compared to predrug recordings and produced a decrease in EEG power >30 Hz but no significant changes were seen within ±20 seconds of losing the righting reflex. By contrast, KSEB 01-S2 produced a significant increase in theta frequency percent power (median 14.7%, 16.2/13.8, 75/25 confidence interval; to 34.7%, 35/31.8; P < .015) and a significant decrease in low gamma frequency percent power (16.9%, 18.6/15.8; to 5.45%, 5.5/5.39; P < .015) for all rats at ± 20 seconds of loss of consciousness (LOC). Both anesthetics produced a flattening of chaotic attractor plots from nonlinear dynamic analyses, like that produced by volatile and dissociative anesthetics at LOC. CONCLUSIONS: KSEB 01-S2 produced a markedly different EEG pattern, with a selective increase observed in the theta frequency range. KSEB 01-S2 also differs markedly in its activity at the GABAAR-slow receptor subtype, suggesting a possible mechanistic link between receptor subtype specificity and EEG frequency band signatures. Increased theta together with depressed gamma frequencies is interesting because GABAAR slow synapses have previously been suggested to underlie theta frequency oscillations, while fast synapses control gamma activity. These reciprocal effects support a previous model for theta and nested gamma oscillations based on inhibitory connections between GABAAR fast and slow interneurons. Although each anesthetic produced a unique EEG response, propofol and KSEB 01-S2 both increased slow wave activity and flattened chaotic attractor plots at the point of LOC.