Huanglian Jiedu decoction (HLJD) has been used to treat ischemic stroke in clinic. However, the detailed protective mechanisms of HLJD on ischemic stroke have yet to be elucidated. The aim of this study is to elucidate the underlying pharmacological mechanisms of HLJD based on the inhibition of neuroinflammation and the amelioration of nerve cell damage. A middle cerebral artery occlusion reperfusion (MCAO/R) model was established in rats and received HLJD treatment. Effects of HLJD on neurological function was assessed based on Bederson\'s score, postural reflex test and asymmetry score. 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining, Hematein and eosin (HE) and Nissl staining were used to observe the pathological changes in brain. Then, transcriptomics was used to screen the differential genes in brain tissue in MCAO/R model rats following HLJD intervention. Subsequently, the effects of HLJD on neutrophil extracellular trap (NET) formation-related neuroinflammation, gamma-aminobutyric acid (GABA)ergic synapse activation, nerve cell damage and proliferation were validated using immunofluorescence, western blot and enzyme-linked immunosorbent assay (ELISA). Our results showed that HLJD intervention reduced the Bederson\'s score, postural reflex test score and asymmetry score in MCAO/R model rats. Pathological staining indicated that HLJD treatment decreased the cerebral infarction area, mitigated neuronal damage and increased the numbers of Nissl bodies. Transcriptomics suggested that HLJD affected 435 genes in MCAO/R rats. Among them, several genes involving in NET formation and GABAergic synapses pathways were dysregulated. Subsequent experimental validation showed that HLJD reduced the MPO+CitH3+ positive expression area, reduced the protein expression of PAD4, p-P38/P38, p-ERK/ERK and decreased the levels of IL-1β, IL-6 and TNF-α, reversed the increase of Iba1+TLR4+, Iba1+p65+ and Iba1+NLRP3+ positive expression area in brain. Moreover, HLJD increased GABA levels, elevated the protein expression of GABRG1 and GAT3, decreased the TUNEL positive expression area and increased the Ki67 positive expression area in brain. HLJD intervention exerts a multifaceted positive impact on ischemia-induced cerebral injury in MCAO/R rats. This intervention effectively inhibits neuroinflammation by mitigating NET formation, and concurrently improves nerve cell damage and fosters nerve cell proliferation through activating GABAergic synapses.

Drug addiction is a chronic and relapse brain disorder. Psychostimulants such as cocaine and amphetamine are highly addictive drugs. Abuse drugs target various brain areas in the nervous system. Recent studies have shown that the prefrontal cortex (PFC) plays a key role in regulating addictive behaviors. The PFC is made up of excitatory glutamatergic cells and gamma-aminobutyric acid (GABAergic) interneurons. Recently, studies showed that GABA level was related with psychostimulant addiction. In this review, we will introduce the role and mechanism of GABA and γ-aminobutyric acid receptors (GABARs) of the PFC in regulating drug addiction, especially in psychostimulant addiction.

Translating sensory inputs to perceptual decisions relies on building internal representations of features critical for solving complex tasks. Yet, we still lack a mechanistic account of how the brain forms these mental templates of task-relevant features to optimize decision-making. Here, we provide evidence for recurrent inhibition: an experience-dependent plasticity mechanism that refines mental templates by enhancing γ-aminobutyric acid (GABA)-mediated (GABAergic) inhibition and recurrent processing in superficial visual cortex layers. We combine ultrahigh-field (7 T) functional magnetic resonance imaging at submillimeter resolution with magnetic resonance spectroscopy to investigate the fine-scale functional and neurochemical plasticity mechanisms for optimized perceptual decisions. We demonstrate that GABAergic inhibition increases following training on a visual (i.e., fine orientation) discrimination task, enhancing the discriminability of orientation representations in superficial visual cortex layers that are known to support recurrent processing. Modeling functional and neurochemical plasticity interactions reveals that recurrent inhibitory processing optimizes brain computations for perpetual decisions and adaptive behavior.

Cognitive impairment affects 29-67% of patients with neuromyelitis optica spectrum disorder. Previous studies have reported glutamate homeostasis disruptions in astrocytes, leading to imbalances in gamma-aminobutyric acid levels. However, the association between these neurotransmitter changes and cognitive deficits remains inadequately elucidated. Point RESolved Spectroscopy and Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy techniques were utilized to evaluate gamma-aminobutyric acid, glutamate, glutathione levels, and excitation/inhibition balance in the anterior cingulate cortex, posterior cingulate cortex, and occipital cortex of 39 neuromyelitis optica spectrum disorder patients and 41 healthy controls. Cognitive function was assessed using neurocognitive scales. Results showed decreased gamma-aminobutyric acid levels alongside increased glutamate, glutathione, and excitation/inhibition ratio in the anterior cingulate cortex and posterior cingulate cortex of neuromyelitis optica spectrum disorder patients. Specifically, within the posterior cingulate cortex of neuromyelitis optica spectrum disorder patients, decreased gamma-aminobutyric acid levels and increased excitation/inhibition ratio correlated significantly with anxiety scores, whereas glutathione levels predicted diminished executive function. The results suggest that neuromyelitis optica spectrum disorder patients exhibit dysregulation in the GABAergic and glutamatergic systems in their brains, where the excitation/inhibition imbalance potentially acts as a neuronal metabolic factor contributing to emotional disorders. Additionally, glutathione levels in the posterior cingulate cortex region may serve as predictors of cognitive decline, highlighting the potential benefits of reducing oxidative stress to safeguard cognitive function in neuromyelitis optica spectrum disorder patients.

The confinement of transgenic fish is essential to prevent their escape and reproduction in natural ecosystems. Reversible transgenic sterilization is a promising approach to control the reproduction of transgenic fish. Therefore, the present study was conducted to develop a reversibly sterile channel catfish (Ictalurus punctatus) via the transgenic overexpression of the goldfish (Carassius auratus) glutamic acid decarboxylase (GAD) gene driven by the common carp (Cyprinus carpio) β-actin promoter to disrupt normal gamma-aminobutyric acid (GABA) regulation. Three generations of GAD-transgenic fish were produced. All studied generations showed repressed reproductive performance; however, this was not always statistically significant. In F1, 5.4% of the transgenic fish showed a sexual maturity score ≥ 4 (maximum = 5) at five years of age, which was lower (p = 0.07) than that of the control group (16.8%). In the spawning experiments conducted on F1 transgenic fish at six and nine years of age, 45.5% and 20.0% of fish spawned naturally, representing lower values (p = 0.09 and 0.12, respectively) than the percentages in the sibling control fish of the same age (83.3% and 66.7%, respectively). Four of six pairs of the putative infertile six-year-old fish spawned successfully after luteinizing hormone-releasing hormone analog (LHRHa) therapy. Similar outcomes were noted in the three-year-old F2 fish, with a lower spawning percentage in transgenic fish (20.0%) than in the control (66.7%). In one-year-old F2-generation transgenic fish, the observed mean serum gonadotropin-releasing hormone (GnRH) levels were 9.23 ± 2.49 and 8.14 ± 2.21 ng/mL for the females and males, respectively. In the control fish, the mean levels of GnRH were 11.04 ± 4.06 and 9.03 ± 2.36 ng/mL for the females and males, respectively, which did not differ significantly from the control (p = 0.15 and 0.27 for females and males, respectively). There was no significant difference in the estradiol levels of the female transgenic and non-transgenic fish in the one- and four-year-old F2-generation fish. The four-year-old F2-generation male transgenic fish exhibited significantly (p < 0.05) lower levels of GnRH and testosterone than the control fish. In conclusion, while overexpressing GAD repressed the reproductive abilities of channel catfish, it did not completely sterilize transgenic fish. The sterilization rate might be improved through selection in future generations.

OBJECTIVE: To investigate the effects of electroacupuncture combined with paliperidone palmitate long-acting injection (PP-LAI) on withdrawal symptoms and neurotransmitters in methamphetamine (MA) addicts.
METHODS: A total of 109 methamphetamine addicts, who were treated in the hospital from October 2021 to October 2022, were selected. According to the random number table, the patients were divided into the study group (n=54) and the control group (n=55), in which the control group was treated with PP-LAI and the study group was treated with electroacupuncture on the basis of the control group; the methamphetamine withdrawal symptom score scale was used to assess the therapeutic effect before treatment and within 12 months after treatment; the changes of brain neurotransmitters dopamine, γ-aminobutyric acid, serotonin, acetylcholine values were compared between the two groups.
RESULTS: 1) There was no statistical difference in MA withdrawal symptom scores between the two groups before treatment (p>0.05); 2) MA withdrawal symptom scores have a statistically significant difference between the study group and the control group after 3 and 6 months of treatment; 3) dopamine levels in the study group were significantly higher than those in the control group after 6 months of completion of treatment, and γ-aminobutyric acid values and 5- serotonin values in the study group were significantly lower than those in the control group (p<0.05).
CONCLUSIONS: Electroacupuncture combined with PP-LAI can partially improve the withdrawal symptoms and anxiety of methamphetamine addicts. This is a potential treatment for preventing relapse of withdrawal symptoms.

Lowing blood lipid levels with probiotics has good application prospects. This study aimed to isolate probiotics with hypolipidemic efficacy from homemade na dish and investigate their mechanism of action. In vitro experiments were conducted to determine the cholesterol-lowering ability of five isolates, with results showing that Lactiplantibacillus plantarum N4 exhibited a high cholesterol-lowering rate of 50.27% and significant resistance to acid (87%), bile salt (51.97%), and pepsin (88.28%) in simulated gastrointestinal fluids, indicating promising application prospects for the use of probiotics in lowering blood lipids. The findings from the in vivo experiment demonstrated that the administration of N4 effectively attenuated lipid droplet accumulation and inflammatory cell infiltration in the body weight and liver of hyperlipidemic rats, leading to restoration of liver tissue morphology and structure, as well as improvement in lipid and liver biochemical parameters. 16S analysis indicated that the oral administration of N4 led to significant alterations in the relative abundance of various genera, including Sutterella, Bacteroides, Clostridium, and Ruminococcus, in the gut microbiota of hyperlipidemia rats. Additionally, fecal metabolomic analysis identified a total of 78 metabolites following N4 intervention, with carboxylic acids and their derivatives being the predominant compounds detected. The transcriptomic analysis revealed 156 genes with differential expression following N4 intervention, leading to the identification of 171 metabolic pathways through Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Notably, the glutathione metabolism pathway, PPAR signaling pathway, and bile secretion pathway emerged as the primary enrichment pathways. The findings from a comprehensive multi-omics analysis indicate that N4 influences lipid metabolism and diminishes lipid levels in hyperlipidemic rats through modulation of fumaric acid and γ-aminobutyric acid concentrations, as well as glutathione and other metabolic pathways in the intestinal tract, derived from both the gut microbiota and the host liver. This research offers valuable insights into the therapeutic potential of probiotics for managing lipid metabolism disorders and their utilization in the development of functional foods.

CONCLUSIONS: γ-Aminobutyric acid alleviates acid-aluminum toxicity to roots associated with enhanced antioxidant metabolism as well as accumulation and transportation of citric and malic acids. Aluminum (Al) toxicity has become the main limiting factor for crop growth and development in acidic soils and is further being aggravated worldwide due to continuous industrial pollution. The current study was designed to examine effects of GABA priming on alleviating acid-Al toxicity in terms of root growth, antioxidant defense, citrate and malate metabolisms, and extensive metabolites remodeling in roots under acidic conditions. Thirty-seven-day-old creeping bentgrass (Agrostis stolonifera) plants were used as test materials. Roots priming with or without 0.5 mM GABA for 3 days were cultivated in standard nutrient solution for 15 days as control or subjected to nutrient solution containing 5 mM AlCl3·6H2O for 15 days as acid-Al stress treatment. Roots were sampled for determinations of root characteristics, physiological and biochemical parameters, and metabolomics. GABA priming significantly alleviated acid-Al-induced root growth inhibition and oxidative damage, despite it promoted the accumulation of Al in roots. Analysis of metabolomics showed that GABA priming significantly increased accumulations of organic acids, amino acids, carbohydrates, and other metabolites in roots under acid-Al stress. In addition, GABA priming also significantly up-regulated key genes related to accumulation and transportation of malic and citric acids in roots under acid-Al stress. GABA-regulated metabolites participated in tricarboxylic acid cycle, GABA shunt, antioxidant defense system, and lipid metabolism, which played positive roles in reactive oxygen species scavenging, energy conversion, osmotic adjustment, and Al ion chelation in roots.

The gut microbiome plays a fundamental role in metabolism, as well as the immune and nervous systems. Microbial imbalance (dysbiosis) can contribute to subsequent physical and mental pathologies. As such, interest has been growing in the microbiota-gut-brain brain axis and the bioelectrical communication that could exist between bacterial and nervous cells. The aim of this study was to investigate the bioelectrical profile (electrome) of two bacterial species characteristic of the gut microbiome: a Proteobacteria Gram-negative bacillus Escherichia coli (E. coli), and a Firmicutes Gram-positive coccus Enterococcus faecalis (E. faecalis). We analyzed both bacterial strains to (i) validate the fluorescent probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol, DiBAC4(3), as a reliable reporter of the changes in membrane potential (Vmem) for both bacteria; (ii) assess the evolution of the bioelectric profile throughout the growth of both strains; (iii) investigate the effects of two neural-type stimuli on Vmem changes: the excitatory neurotransmitter glutamate (Glu) and the inhibitory neurotransmitter γ-aminobutyric acid (GABA); (iv) examine the impact of the bioelectrical changes induced by neurotransmitters on bacterial growth, viability, and cultivability using absorbance, live/dead fluorescent probes, and viable counts, respectively. Our findings reveal distinct bioelectrical profiles characteristic of each bacterial species and growth phase. Importantly, neural-type stimuli induce Vmem changes without affecting bacterial growth, viability, or cultivability, suggesting a specific bioelectrical response in bacterial cells to neurotransmitter cues. These results contribute to understanding the bacterial response to external stimuli, with potential implications for modulating bacterial bioelectricity as a novel therapeutic target.

BACKGROUND: Changing climate is causing erratic rainfall and prolonged drought periods, thus posing serious threats to crop productivity. Owing to severity of drought events, it is imperative to take proactive measures to enhance the resilience of drought sensitive crops like rice. Therefore, the present study was carried out to improve the drought stress tolerance in rice through gamma amino butyric acid (GABA) application.
METHODS: The experiment was included four GABA concentrations i.e., 0 mM as control, 1 mM, 1.5 mM, and 2 mM, two water levels i.e., 100% and 50% field capacity (referred as FC100 for well-watered and FC50 for drought conditions, respectively), and two fragrant rice cultivars i.e., Super Basmati and Basmati-515.
RESULTS: The findings unveiled a comprehensive improvement in various parameters with GABA application in fragrant rice under both well-watered (FC100) and water-limited (FC50) conditions, compared to the control. Specifically, GABA induced enhancements were observed in plant height, root length, fresh weight, dry weight, total soluble protein content, and total free amino acid content across both cultivars. Moreover, GABA application significantly improved peroxidase (POD) and catalase (CAT) enzyme activities, alongside elevating anthocyanin levels, while concurrently reducing H2O2 contents in both FC100 and FC50 treatments. Furthermore, the positive impact of GABA extended to morphological traits, with notable increases in panicle length, total tillers and productive tillers per hill, branch and grain numbers per panicle, and 1000-grain weight for Super Basmati and Basmati 515 cultivars under both water regimes, compared to Ck. Similarly, the grain yield increased by 31.01% and 27.32% under FC100 and 36.85% and 27.71% under FC50 in Super Basmati and Basmati-515, respectively, in response to GABA application, compared to Ck. Additionally, principal component analysis (PCA) revealed significant variances attributed to Dim1 and Dim2, with 86.1% and 4.0% of the variance, respectively, across three bi-plots encompassing rice cultivars, water levels, and GABA treatments. Notably, all tested indices, except for H2O2 and non-productive tillers per hill, exhibited positive correlations amongst themselves and with rice yield, further emphasizing the beneficial effects of GABA application on fragrant rice under well-watered and drought conditions.
CONCLUSIONS: GABA significantly improved fragrant rice performance under both well-watered (FC100) and water-limited (FC50) conditions. Moreover, integrating GABA application into rice cultivation practices could not only improve the crop resilience to drought stress but also potentially benefiting the future food and nutritional security globally. However, however; further research is needed to understand the cellular and molecular mechanisms of the functionality of GABA in fragrant rice, particularly under drought conditions.