Gamma-aminobutyric Acid Levels Research Articles

Neural response to stress differs by sex in young adulthood

Increase in stress-related disorders in women begins post-puberty and persists throughout the lifespan. To characterize sex differences in stress response in early adulthood, we used functional magnetic resonance imaging while participants underwent a stress task in conjunction with serum cortisol levels and questionnaires assessing anxiety and mood. Forty-two healthy subjects aged 18–25 years participated (21M, 21F). Interaction of stress and sex in brain activation and connectivity were examined. Results demonstrated significant sex differences in brain activity with women exhibiting increased activation in regions that inhibit arousal compared to men during the stress paradigm. Women had increased connectivity among stress circuitry regions and default mode network, whereas men had increased connectivity between stress and cognitive control regions. In a subset of subjects (13F, 17M), we obtained gamma-aminobutyric acid (GABA) magnetic resonance spectroscopy in rostral anterior cingulate cortex (rostral ACC) and dorsolateral prefrotal cortex (dlPFC) and conducted exploratory analyses to relate GABA measurements with sex differences in brain activation and connectivity. Prefrontal GABA levels were negatively associated with inferior temporal gyrus activation in men and women and with ventromedial prefrontal cortex activation in men. Despite sex differences in neural response, we found similar subjective ratings of anxiety and mood, cortisol levels, and GABA levels between sexes, suggesting sex differences in brain activity result in similar behavioral responses among the sexes. These results help establish sex differences in healthy brain activity from which we can better understand sex differences underlying stress-associated illnesses.

Electroacupuncture of the cymba concha alleviates p-chlorophenylalanine-induced insomnia in mice.

Insomnia is the most common sleep disorder and is often comorbid with mental and physical diseases. The present study was designed to investigate the hypnotic effect of electroacupuncture (EA) of the cymba concha to stimulate the auricular branch of the vagus nerve (ABVN). Mice were intraperitoneally injected with p-chlorophenylalanine (PCPA, 300 mg/kg·d) for 2 days to induce insomnia and subsequently received EA or manual acupuncture (MA) of the cymba concha for 30 min once daily for 5 consecutive days, or no treatment. The phenobarbital-induced sleep test was used to analyze the hypnotic effects and the open field test was used to analyze the locomotor activities and anxiolytic effects of EA/MA of the cymba concha. In addition, the levels of gamma-aminobutyric acid (GABA) and glutamate (Glu) in the hypothalamus and peripheral blood were determined by enzyme-linked immunosorbent assay (ELISA). PCPA injection significantly decreased sleep duration, increased sleep latency and induced anxiety-like behaviors in mice. In PCPA-insulted mice, EA of the cymba concha improved the sleep disturbance by significantly prolonging sleep duration, while no change in sleep latency was observed. Moreover, EA of the cymba concha improved PCPA-induced anxiety-like behaviors without decreasing locomotor activities in the open field test. EA of the cymba concha increased the level of GABA in the hypothalamus and peripheral blood, while Glu concentrations remained unchanged. These findings indicate that EA of the region innervated by the ABVN upregulates GABA levels in the hypothalamus and ameliorates the symptoms of insomnia and anxiety, suggesting that EA of the cymba concha might have potential value as an intervention for insomnia.

Gabaergic System in the Regulation of the Functioning of Pancreas Beta-Cells in Normal Physiological Conditions and in Diabetes

Abstract—The incidence of diabetes mellitus (DM) is steadily increasing all over the world, and at the same time there is an increase in its complications, which are the main causes of early disability and premature death. The pathogenesis of DM is based on a steady decrease in pancreatic β-cells. A decrease in β-cell mass leads to a decrease in insulin production and the development of hyperglycemia and associated severe complications. Therefore, the need to prevent the death of β-cells and stimulate their regeneration is obvious. In recent literature, much attention has been paid to the role of GABA in the regulation of the function of α- and β-cells of the pancreas and carbohydrate metabolism, which is the subject of this review. Gamma-aminobutyric acid (GABA) in β-cells and pancreatic islets is determined in quantities comparable to those in the brain. It also contains a high amount of glutamadecarboxylase, an enzyme that synthesizes GABA. In DM, the level of GABA in pancreatic β-cells decreases and this correlates with the severity of DM. GABA plays an important role in the paracrine regulation of α- and β-cell functions and carbohydrate homeostasis. The potential possibility of using GABA to achieve a decrease in apoptosis and, at the same time, an increase in the regeneration of β-cells, an increase in the β-cell mass of the pancreas has been proven. It has been proven that the positive effect of GABA on the structure and functions of pancreatic β-cells in DM can be significantly higher when combined with antidiabetic agents: GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitors, and others. The antidiabetic properties of GABA are explained by its interaction with various signaling proteins (Kloto protein, SIRT, PI3K/Akt, CREB-IRS2, NF-kB, Nrf2 and many others), through which these effects are realized. Data on the pancreatic protective effect of GABA and its derivatives can form the basis for the development of a new pharmacotherapeutic strategy for the treatment of DM and associated complications.

Chemical Composition and Hypnotic Effect of Picea mariana Essential Oils

With rapid economic development, social competition has become increasingly intense. Stress experienced by individuals has increased dramatically, resulting in a steady rise in insomnia. The present study investigated the effect of different concentrations of Picea mariana essential oils (PMEOs) on sleep improvement in mice exhibiting p-chlorophenylalanine (PCPA)-induced insomnia. First, the main constituents of PMEOs were analyzed by gas chromatography-mass spectrometry (GC-MS). The mice were weighed daily, and the sleep latency and duration were measured in each mouse group in the inverted reflex experiment. The number of neurons in the mouse brain was measured using Nissl staining. The expression level of 5-hydroxytryptamine-1A (5-HT1A) was determined by immunohistochemistry, whereas the expression level of gamma-aminobutyric acid A receptor subunit alpha-1 (GABAARɑ1) was detected by immunohistochemistry, western blotting, and reverse transcription-quantitative PCR (RT-qPCR). GC-MS identified the top five components comprising PMEOs as bornyl acetate, camphene, α-pinene, β-pinene, and 3-carene. Inhalation of PMEOs resulted in a progressive increase in the rate of body weight change, a decrease in sleep latency, and prolonged sleep duration in experimental mice. In Nissl staining, the number of neurons was significantly reduced in the PCPA group when compared with the elevated number in the PMEOs group. Immunohistochemistry revealed increased expression levels of GABAARα1 and 5-HT1A in the PMEOs group. Western blotting and RT-qPCR results showed increased levels of GABAARα1 protein and gene expression, respectively. PMEOs could increase GABAARα1 and 5-HT1A protein levels in mice, resulting in hypnotic effects.

Hydroxy proline and gamma-aminobutyric acid: markers of susceptibility to vine decline disease caused by the fungus Monosporascus cannonballus in melons (Cucumis melo L.).

Vine decline disease caused by the fungus Monosporascus cannonballus, is a threat to melon production (Cucumis melo L.) worldwide. Nonetheless, little is known about the metabolites produced during the host pathogen interaction. Thus, the objective of this study was to measure quantities of amino acids produced over time during such an interaction. Two melon genotypes named TAM-Uvalde (susceptible) and USDA PI 124104 (resistant) were grown and inoculated with M. cannonballus. The metabolites previously stated were measured before inoculation (0 hours) and 24, 48 and 72 hours after inoculation, using high performance liquid chromatography analysis. The production of some amino acids during the interaction of the resistant and susceptible melon genotypes with the fungus M. cannonballus was different regarding quantities over time. Interestingly, hydroxy proline was always up-regulated in higher quantities in response to pathogen infection in the genotype TAM-Uvalde. Also, the up-regulation in higher quantities of gamma-aminobutyric acid in the genotype TAM-Uvalde 48 and 72 hours after inoculation, suggests more penetration of the pathogen in its roots. Hence, taken together, hydroxy proline and gamma-aminobutyric acid levels could be used as markers of susceptibility to vine decline disease caused by M. cannonballus, which could be useful in developing resistant varieties.

The changes in Gamma-aminobutyric acid and polyphenols in mung beans (Vigna radiata L.) during germination

Gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, plays a role in regulating neuronal excitability. Polyphenols naturally occur in plants and help to prevent or reverse damage in cells caused by aging, the environment, and lifestyle. Edible sprouts such as mung beans are a valuable source that presents high content of bioactive compounds. These contents in raw mung beans are very low, but they increase significantly during germination. The objectives of this study were to determine the most appropriate germination conditions, including air relative humidity (80%, 90%, and 99%), salt concentrations (0, 0.5%, 1.0%, and 1.5%), and light conditions (dark, LED, and UV-C) during the soaking and incubation processes to maximize the content of GABA and polyphenols. The results showed that all investigated treatments (air relative humidity, salt, and light) increased GABA and polyphenol levels, but LED lighting and air relative humidity of 90% were the most effective. Under those conditions, the content of GABA and polyphenols in the germinated mung beans increased about 12 and 2 times, respectively. Furthermore, the changes in GABA and polyphenol contents were different under different soaking and incubation conditions. In conclusion, the nutritional quality of mung beans, in terms of GABA and polyphenols, could be improved by controlling light and air relative humidity during germination. It is also recommended that the germination conditions, including air relative humidity, soaking in water or salt, soaking time, and incubation time should be selected depending on the desired content of GABA or polyphenols.

Altered glutamate-glutamine and amide proton transfer-weighted values in the hippocampus of patients with amnestic mild cognitive impairment: A novel combined imaging diagnostic marker.

Early diagnosis of amnestic mild cognitive impairment (aMCI) and timely management to delay the onset of Alzheimer's disease (AD) would benefit patients. Pathological metabolic changes of excitatory/inhibitory neurotransmitters and abnormal protein deposition in the hippocampus of aMCI may provide a new clue to imaging diagnosis. However, the diagnostic performance using these hippocampal metabolite measurements is still unclear. We aimed to quantify right hippocampal glutamate-glutamine (Glx) and gamma-aminobutyric acid (GABA) levels as well as protein-based amide proton transfer-weighted (APTw) signals of patients with aMCI and investigate the diagnostic performance of these metabolites. In this cross-sectional study, 20 patients with aMCI and 20 age- and gender-matched healthy controls (HCs) underwent MEGA Point Resolved Spectroscopy (MEGA-PRESS) and APTw MR imaging at 3 T. GABA+, Glx, and APTw signals were measured in the right hippocampus. The GABA+ levels, Glx levels, Glx/GABA+ ratios, and APTw values were compared between the HCs and aMCI groups using the Mann-Whitney U test. Binary logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate MEGA-PRESS and APTw parameters' diagnostic performance. Compared with HCs, patients with aMCI had significantly lower Glx levels in the right hippocampus (7.02 ± 1.41 i.u. vs. 5.81 ± 1.33 i.u., P = 0.018). No significant changes in the GABA+ levels were observed in patients with aMCI (HCs vs. aMCI: 2.54 ± 0.28 i.u. vs. 2.47 ± 0.36 i.u., P = 0.620). In addition, Glx/GABA+ ratios between the two groups (HCs vs. aMCI: 2.79 ± 0.60 vs. 2.37 ± 0.55, P = 0.035) were significantly different. Compared with HCs, patients with aMCI showed higher APTw values in the right hippocampus (0.99 ± 0.26% vs. 1.26% ± 0.28, P = 0.006). The ROC curve analysis showed that Glx, GABA+, Glx/GABA+, and APTw values had an area under the curve (AUC) of 0.72, 0.55, 0.70, and 0.75, respectively, for diagnosing aMCI. In the ROC curve analysis, the AUC of the combination of the parameters increased to 0.88, which is much higher than that observed in the univariate analysis (P < 0.05). The combination of right hippocampal Glx levels and APTw values improved the diagnostic performance for aMCI, indicating it as a promising combined imaging diagnostic marker. Our study provided a potential imaging diagnostic strategy of aMCI, which may promote early detection of aMCI and facilitate timely intervention to delay the pathological progress toward AD.

Patterns of developmental regression and associated clinical characteristics in SLC6A1-related disorder.

SLC6A1-related disorder is a genetic neurodevelopmental disorder that is caused by loss of function variants in the SLC6A1 gene. Solute Carrier Family 6 Member 1 (SLC6A1) gene encodes for gamma-aminobutyric acid (GABA) transporter type 1 (GAT1), which is responsible for reuptake of GABA from the synaptic cleft. Tight regulation of GABA levels plays an important role in brain development by balancing inhibitory and excitatory neuronal signaling. Consequently, individuals with SLC6A1-related disorder can have manifestations such as developmental delay, epilepsy, autism spectrum disorder, and a subset have developmental regression. In this study, we identified patterns of developmental regression among a cohort of 24 patients with SLC6A1-related disorder and assessed for clinical characteristics associated with regression. We reviewed medical records of patients with SLC6A1-related disorder and divided subjects into two groups: 1) regression group and 2) control group. We described the patterns of developmental regression including whether there was a trigger prior to the regression, multiple episodes of regression, and whether or not skills were recovered. We assessed the relationship of clinical characteristics among the regression and control groups including demographic factors, seizures, developmental milestone acquisition, gastrointestinal problems, sleep problems, autism spectrum disorder, and behavioral problems. Individuals with developmental regression had a loss of skills that were previously mastered in developmental domains including speech and language, motor, social, and adaptive skills. The mean age at regression was 2.7 years and most subjects had regression of language or motor skills triggered by seizures, infection, or spontaneously. Although there was no significant difference in clinical characteristics between the two groups, there was a higher prevalence of autism and severe language impairment in the regression group. Future studies of a larger cohort of patients are required to make definitive conclusions. Developmental regression is often a sign of severe neurodevelopmental disability in genetic syndromes, but it is poorly understood in SLC6A1-related disorder. Understanding the patterns of developmental regression and the associated clinical characteristics in this rare disorder will be important to medical management, prognostication, and could impact the design of future clinical trials.

Chronic exposure to environmentally relevant concentrations of carbamazepine interferes with anxiety response of adult female zebrafish through GABA /5-HT pathway and HPI axis

Carbamazepine (CBZ) is one of the widely distributed pharmaceutical residues in aquatic environments, yet few researches have addressed its chronic effect on the anxiety of fish, and the mechanisms possibly involved remained elusive. In this study, adult female zebrafish (Danio rerio) were exposed to environmental relevant concentrations of CBZ (CBZ-low, 10 μg/L; CBZ-high, 100 μg/L) for 28 days. After exposure, CBZ-high didn't affect the anxiety of fish. However, the onset time to the higher half of the tank was delayed and the total duration in the lower half of the tank was increased in CBZ-low fish, suggesting an increased anxiety. Further investigation indicated that CBZ-low significantly decreased the gamma-aminobutyric acid (GABA) level in the brain, while increased the serotonin (5-HT) level in the brain and cortisol level in plasma. Accordingly, the mRNA levels of genes in GABA (gad2, abat, gabrb2, gabrg2, gria1a and slc12a2) pathway and HPI (crha, actha, pc1 and pc2) axis were also altered. Despite the upregulation of tph2 was consistent with increased 5-HT level in the brain, significantly downregulated htr1aa and htr1b may indicate attenuated 5-HT potency. Although CBZ-high significantly reduced GABA level in the brain and increased cortisol level in plasma, the effects were dramatically alleviated than that of CBZ-low. Consistently, the expression of genes in HPI (crha, actha, pc1 and pc2) axis and GABA (gad2 and abat) pathway were also altered by CBZ-high, probably due to inconspicuous anxiety response of CBZ-high. Briefly, our data suggested that low concentration of CBZ disrupted zebrafish anxiety by interfering with neurotransmission and endocrine system, thereby bringing about adverse ecological consequences.

Intragastric administration of prednisone acetate induced impairment of hippocampal long-term potentiation

Prednisone acetate (PA) has many adverse side effects despite the fact that oral administration of PA is widely administrated in the clinic. However, it is unknown whether PA can cause hippocampal long-term potentiation (LTP) impairment. Therefore, in our study, PA (5 mg/kg·d) through intragastric administration (gavage) was applied to establish a model of impaired hippocampal LTP in C57BL/6 mice, and the method was evaluated by comparing with another method to establish LTP impairment through subcutaneous injection of corticosterone (CORT, 50 mg/kg·d). First, our results showed PA caused a more significant decrease in population spike (PS, %) after high-frequency stimulation (HFS) than CORT, demonstrating PA induced impairment of hippocampal LTP more successfully than CORT. Second, PA caused poorer performance of memory than CORT. Third, PA caused more serious lesions and loss of the granule cell in the dentate gyrus than CORT. Finally, PA caused lower levels of glutamic acid (Glu), N-methyl-d-aspartate receptors (NMDARs) and gamma-aminobutyric acid (GABA) than CORT. All in all, PA (5 mg/kg·d) through intragastric administration (gavage) induced LTP impairment in the hippocampus more successfully than CORT. The neuronal lesions in the dentate gyrus and the consequent decrease of Glu and NMDARs (especially NMDAR2A) may be the cause of LTP impairment.

Improvement of Caciotta-like cheese nutritional value by means of enrichment with blackcurrant (Ribes nigrum) and Cornelian cherry (Cornus mas).

In this study, we supplemented models of Caciotta-like cheese with blackcurrant (Ribes nigrum) and Cornelian cherry (Cornus mas), as they have a high content of polyphenols, known as phytochemicals associated with health benefits. We evaluated the microbial composition, organoleptic aspects, total phenolic content, and chemical composition of model cheeses enriched with blackcurrant and Cornelian cherry. Two different suppliers have been tested: a conventional and an organic one. Two different conditions of preparation (freeze-dried and not freeze-dried) were tested in two different amounts (0.3 and 0.6% dry weight w/v milk volume). Polyphenols were determined using Folin-Ciocalteu reaction and spectrometry; microbial community was determined with selective 24 media and plate counts; composition was determined using nuclear magnetic resonance spectrometry. Organoleptic tests with an untrained panel have been performed. The enrichments with blackcurrant and Cornelian cherry increased the total polyphenol content in model cheeses, in particular, when blackcurrant and Cornelian cherry were from conventional farming. Blackcurrant-enriched cheeses showed higher counts of lactic acid bacteria, higher levels of organic acids, amino acids, gamma-aminobutyric acid, histamine, and lower amount of monosaccharides deriving from bacterial lactose fermentation in cheese, suggesting a positive effect of blackcurrant compounds on the growth and activity of lactic acid bacteria. The enrichments did not affect the acceptance of the cheese, neither by blackcurrant nor by Cornelian cherry incorporation, with the exception of the appearance. Overall, we showed that cheeses enriched with blackcurrant or Cornelian cherry from conventional farming increased the bioactive potential of the dairy product without having an adverse effect on the microbial community, physiochemical properties, or organoleptic properties.

Effect of berrycactus fruit (Myrtillocactus geometrizans) on glutamate, glutamine, and GABA levels in the frontal cortex of rats fed with a high-fat diet.

In addition to the known metabolic alterations, obesity has consequences at the brain level, driving imbalance in neurotransmitters such as glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA). The consumption of fruits with antioxidant properties, such as the berrycactus Myrtillocactus geometrizans, could have beneficial effects in such an imbalance. The study objective was to evaluate frontal cortex neurotransmitter levels and weight changes in rats fed with a high-fat diet (HFD) and MG. To achieve that, five groups of Wistar rats received different diets for 24 weeks: standard diet (SDt), HFD, HFD + MG extract 150 mg (HMg150), HFD + MG extract 300 mg (HMg300), and HFD + MG extract 450 mg (HMg450); rats received MG extract for the last 4 weeks. Weight and food intake were recorded every week, and also neurotransmitter levels were quantified using high-performance liquid chromatography. Groups fed with HFDs had increased Glu and Gln levels, decreased GABA, and also gained more weight compared to the SDt group; MG extract of 450 mg decreased Glu levels. Concentrations of 300 and 450 mg of MG extract decreased weight compared to the HFD and HMg150 groups. This study reports that HFDs have an impact on neurotransmitter levels and weight, MG extract showed a reduction in Glu concentration and weight.

Cerebellar gamma-aminobutyric acid: Investigation of group effects in neurodevelopmental disorders.

Neurodevelopmental disorders (NDDs) including autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) are thought to arise in part from the disruption in the excitatory/inhibitory balance of gamma-aminobutyric acid (GABA) and glutamate in the brain. Recent evidence has shown the involvement of the cerebellum in cognition and affect regulation, and cerebellar atypical function or damage is reported frequently in NDDs. Magnetic resonance spectroscopy studies have reported decreases in GABA in cortical brain areas in the NDDs, however, GABA levels in the cerebellum have not been examined. To determine possible group effects, we used a MEGA-PRESS acquisition to investigate GABA+ levels in a cerebellar voxel in 343 individuals (aged 2.5-22 years) with ASD, ADHD, OCD and controls. Using a mixed effects model, we found no significant differences between groups in GABA+ concentration. Our findings suggest that cerebellar GABA+ levels do not differentiate NDD groups.

Gamma-Aminobutyric Acid-Producing Levilactobacillus brevis Strains as Probiotics in Litchi Juice Fermentation.

Levilactobacillus brevis strains can be isolated from traditional Chinese pickles and used as the starter cultures to improve the nutritional profiles of fermented juices. Three L. brevis strains (LBG-29, LBG-24, LBD-14) that produce high levels of gamma-aminobutyric acid (GABA; &gt;300 mg/L) were isolated from traditional Chinese pickles. The strains showed tolerance to low pH and high bile salts and exhibited safety in vitro. Litchi juice was fermented using each strain at 37 °C for 48 h. The litchi juice was determined to be a good substrate for fermentation as the process enhanced its functional profile. Overall, cell vitality increased (above 8.7 log10 CFU/mL), the antioxidant activities of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion-reducing antioxidant power (FRAP) were significantly increased, and the antioxidant capacity of the 2,2'-amino-di(3-ethyl-benzothiazoline sulphonic acid-6)ammonium salt (ABTS) was decreased. There was also a significant increase in the GABA and acetic acid content after LBG-29 and LBG-24 fermentation. It was thus determined that the LBG-29 and LBG-24 strains could be used to improve beverage functionality and aid in the development of new products. This is the first report of litchi fermentation using L. brevis as a starter culture. Further research is required to elucidate the functional benefits for the human body and the nutritional and functional properties during its shelf life.

Neurochemical and functional reorganization of the cognitive-ear link underlies cognitive impairment in presbycusis

Recent studies suggest that the interaction between presbycusis and cognitive impairment may be partially explained by the cognitive-ear link. However, the underlying neurophysiological mechanisms remain largely unknown. In this study, we combined magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (fMRI) to investigate auditory gamma-aminobutyric acid (GABA) and glutamate (Glu) levels, intra- and inter-network functional connectivity, and their relationships with auditory and cognitive function in 51 presbycusis patients and 51 well-matched healthy controls. Our results confirmed reorganization of the cognitive-ear link in presbycusis, including decreased auditory GABA and Glu levels and aberrant functional connectivity involving auditory networks (AN) and cognitive-related networks, which were associated with reduced speech perception or cognitive impairment. Moreover, mediation analyses revealed that decreased auditory GABA levels and dysconnectivity between the AN and default mode network (DMN) mediated the association between hearing loss and impaired information processing speed in presbycusis. These findings highlight the importance of AN-DMN dysconnectivity in cognitive-ear link reorganization leading to cognitive impairment, and hearing loss may drive reorganization via decreased auditory GABA levels. Modulation of GABA neurotransmission may lead to new treatment strategies for cognitive impairment in presbycusis patients.

Detection of physiological concentrations of GABA using dielectric spectroscopy - A pilot study.

Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that is present at a relatively low level throughout the normal adult human brain. Abnormal GABA levels are found in people with neurodegenerative disorders such as Parkinson's disease, epilepsy, schizophrenia, depression, and others. Being able to measure the GABA concentration would be beneficial for patient groups with fluctuating GABA levels for better diagnosis and treatment. In this study, we explore the feasibility of using dielectric relaxation spectroscopy for the detection of GABA concentrations within a physiological range, with the perspective of miniaturization and use during implantation. Utilizing machine learning techniques, we were able to differentiate GABA concentrations down to 5 μm. This work investigates a novel use of dielectric relaxation spectroscopy, to assess if physiological GABA concentrations can be detected through permittivity measurements.

Anticonvulsant effects of desvenlafaxine on modulating brain monoamine and oxidative stress in mice.

Desvenlafaxine succinate (DVS) inhibits serotonin reuptake selectively and is approved for major depressive disorders. This research investigated influence of DVS on modulating brain monoamine and oxidative stress in mice. The antiepileptic potential of DVS (10, 20, or 30 mg/kg/i.p.) in pentylenetetrazole (PTZ; 85 mg/kg) with i.p. route of administration, strychnine (STR; 75 mg/kg) with i.p. route, pilocarpine (400 mg/kg) with s.c. route and maximal electroshock MES-induced convulsion in mouse models. The activities of oxidative stress, i.e. superoxide dismutase (SOD), glutathione (GSH) and lipid peroxidation (LPO) as well as gamma-aminobutyric acid (GABA) in the brains of PTZ-induced convulsive mice. Treatment with DVS increased the latency to develop siezures and declined mortalities in rodents against PTZ, STR and pilocarpine-induced convulsions. Results of MES-leaded siezures revealed that DVS reduced tonic hind limb extension duration and mortalities significantly. Brain, SOD, GSH and GABA level were significantly (P<0.01) increased and LPO reduced significantly (P<0.01) after DVS treatment. Furthermore, the DVS did not show any motor coordination signs in the rotarod test. We demonstrated that the role of DVS in convulsion genesis in mice under control condition and attenuate the PTZ-induced oxidative damage.

Changes in gamma-aminobutyric acid and glutamate/glutamine levels in the right thalamus of patients with episodic and chronic migraine: A proton magnetic resonance spectroscopy study.

To explore gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels in the right thalamus of patients with episodic migraine (EM) and chronic migraine (CM) and their effects on the chronification of migraine. Migraine affects approximately 1 billion people worldwide, with 2.5%-3% of people with EM progressing to CM each year. Magnetic resonance spectroscopy studies have revealed altered GABA and Glx levels in the thalamus of patients with migraine without aura, but these neurometabolic concentrations are underexplored in the thalamus of patients with CM. In this cross-sectional study, patients with EM and CM were recruited. Mescher-Garwood point resolved spectroscopy sequence was used to acquire neurotransmitter concentrations in the right thalamus of patients with EM and CM and matched healthy controls (HCs). A total of 26 patients (EM, n= 11; CM, n= 15) and 16 age- and sex-matched HCs were included in the analysis. There were significantly lower GABA+/Water levels in the right thalamus of the CM group (mean ± standard deviation: 2.27 ± 0.4 [institutional units]) than that of the HC group (2.74 ± 0.4) (p= 0.026; mean difference [MD]=-0.5 [i.u.]), and lower Glx/Cr levels in the EM group (mean ± SD: 0.11 ± < 0.1) than in the HCs (0.13 ± < 0.1) and CM group (0.13 ± < 0.1) (p= 0.023, MD < -0.1, and p= 0.034, MD < -0.1, respectively). The GABA+/Glx ratio was lower in the CM group (mean ± SD: 0.38 ± 0.1) compared to the EM group (0.47 ± 0.1) (p= 0.024; MD=-0.1). The area under the curve for GABA+/Water levels in differentiating patients with CM from HCs was 0.83 (95% confidence interval 0.68, 0.98; p= 0.004). Correlation analyses within the migraine group revealed no significant correlation between metabolite concentration levels and headache characteristics after Bonferroni correction. Reduced GABA+/Water levels and imbalance of excitation/inhibition in the right thalamus may contribute to migraine chronification.

Effects of calmodulin overexpression on gamma-aminobutyric acid (GABA) levels and glutamate decarboxylase activity in rice seedlings

Effects of calmodulin overexpression on gamma-aminobutyric acid (GABA) levels and glutamate decarboxylase activity in rice seedlings

Microbiome-metabolomics analysis reveals the potential effect of verbascoside in alleviating cognitive impairment in db/db mice.

Cognitive impairment is the main central nervous system complication of diabetes, affecting the quality of life of patients. Herba Cistanche is a homologous plant widely used as a health food and therapeutic drug. Verbascoside, a signature component of Herba Cistanche, has anti-diabetic and neuroprotective effects. However, it is quickly metabolized by the gut microbiota, and the mechanism of its neuroprotection and improvement of learning and memory remains unclear. We investigated the effectiveness and potential mechanisms of verbascoside on cognitive dysfunction in db/db mice using a 16S rRNA microbiome and serum metabolomics approach. We found that 12-week treatment with verbascoside significantly inhibited insulin resistance, reduced blood glucose and lipids, and improved cognitive deficits. In addition, verbascoside increased the gut microbiota diversity, improved intestinal dysbiosis, attenuated intestinal barrier disruption, reduced the levels of inflammatory factors, regulated the expression of the metabolites associated with cognitive function, and enhanced the central insulin sensitivity and hippocampal synaptogenesis signaling. We revealed that verbascoside induced the enrichment of Alistipes, Roseburia, and Intestinimonas in the gut, suppressed the abundance of Escherichia-Shigella, increased the serum levels of gamma-aminobutyric acid, L-glutamic acid, and L-lysine, and decreased taurine expression. Finally, a strong association between gut microbes, serum metabolites, and cognitive performance affected by verbascoside was observed. Our research suggests that alterations in gut microbes/metabolites are involved in the development of diabetic cognitive dysfunction, which is alleviated by verbascoside in the db/db mice through restructuring the gut microbiota composition, ameliorating diabetic metabolic disorders, and attenuating pathological brain damage.