Gamma-aminobutyric Acid Levels Research Articles

Potent γ-amino butyric acid producing psychobioticLactococcus lactis LP-68 from non-rhizospheric soil of Syzygium cumini (Black plum).

Gamma amino butyric acid (GABA) is a chemical messenger that plays a significant role in muscle relaxation and brain health. Certain lactic acid bacteria (LAB) produce significant levels of GABA and thus act as potential psychobiotic cultures. In the present study, LAB were isolated from non-rhizospheric soil sample of Syzygium cumini (Black plum). A total of 57 LAB were isolated on the basis of their morphological and acid producing characteristic on de Man Rogosa Sharpe (MRS) agar. Only seven isolates were found to produce GABA (0.09-1.13gL-1) in MRS broth and were identified as Lactococcus. However, L. lactis LP-68 produced highest amount of GABA and was selected for further optimization of culture conditions (pH, temperature and MSG) by response surface methodology (RSM). The optimization resulted in approximately four-fold increase in GABA production (4.11gL-1). The results indicate that the L. lactis LP-68 can be used as starter culture for production of GABA-enriched functional foods.

Ketogenic Therapy for Major Depressive Disorder: A Review of Neurobiological Evidence

Major depressive disorder (MDD) is a debilitating illness that places a great burden on global health. A ketogenic diet, which has traditionally been used for treating refractory epileptic disorders, is being increasingly explored for its potential of alleviating other neuropsychiatric conditions. Providing an up-to-date summary on the ketogenic diet’s potential to alleviate MDD, its neurobiological basis, and preliminary clinical evidence. A structured literature survey was performed, and a narrative review was written. Basic science provides cues for the biological mechanisms underlying the antidepressant effects of ketosis. Ketosis may circumvent frontal cortical glucose hypometabolism, reduce oxidative stress and neuroinflammation, and restore neurotransmitter homeostasis by increasing gamma-aminobutyric acid (GABA) levels and decreasing excitatory neurotransmitter levels. Another interesting domain affected by ketosis and potentially linked to mood and mental health is the gut microbiome. Emerging clinical evidence supports the efficacy of ketosis induction in treating patients with mood disorders. Evidence supports the antidepressant potential of the ketogenic diet. However, further substantial research into the underlying mechanisms of action and clinical effects is required.

Left Dorsolateral Prefrontal Cortex Glx/tCr Predicts Efficacy of High Frequency 4- to 6-Week rTMS Treatment and Is Associated With Symptom Improvement in Adults With Major Depressive Disorder: Findings From a Pilot Study.

About 20–40% of estimated 121 million patients with major depressive disorder (MDD) are not adequately responsive to medication treatment. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive, non-convulsive neuromodulation/neurostimulation method, has gained popularity in treatment of MDD. Because of the high cost involved in rTMS therapy, ability to predict the therapy effectiveness is both clinically and cost wise significant. This study seeks an imaging biomarker to predict efficacy of rTMS treatment using a standard high frequency 10-Hz 4- to 6-week protocol in adult population. Given the significance of excitatory and inhibitory neurotransmitters glutamate (Glu) and gamma aminobutyric acid (GABA) in the pathophysiology of MDD, and the involvement of the site of rTMS application, left dorsolateral prefrontal cortex (lDLPFC), in MDD, we explored lDLPFC Glx (Glu + glutamine) and GABA levels, measured by single voxel magnetic resonance spectroscopy (MRS) with total creatine (tCr; sum of creatine and phosphocreatine) as reference, as possible biomarkers of rTMS response prediction. Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) MRS data from 7 patients (40–74 y) were used in the study; 6 of these patients were scanned before and after 6 weeks of rTMS therapy. Findings from this study show inverse correlation between pretreatment lDLPFC Glx/tCr and (i) posttreatment depression score and (ii) change in depression score, suggesting higher Glx/tCr as a predictor of treatment efficacy. In addition association was observed between changes in depression scores and changes in Glx/tCr ratio. The preliminary findings did not show any such association between GABA/tCr and depression score.

Increase in ACC GABA+ levels correlate with decrease in migraine frequency, intensity and disability over time

BackgroundAn imbalance between inhibitory and excitatory neurometabolites has been implicated in chronic pain. Prior work identified elevated levels of Gamma-aminobutyric acid + macromolecules (“GABA+”) using magnetic resonance spectroscopy (MRS) in people with migraine. What is not understood is whether this increase in GABA+ is a cause, or consequence of living with, chronic migraine. Therefore, to further elucidate the nature of the elevated GABA+ levels reported in migraine, this study aimed to observe how GABA+ levels change in response to changes in the clinical characteristics of migraine over time.MethodsWe observed people with chronic migraine (ICHD-3) over 3-months as their treatment was escalated in line with the Australian Pharmaceutical Benefits Scheme (PBS). Participants underwent an MRS scan and completed questionnaires regarding migraine frequency, intensity (HIT-6) and disability (WHODAS) at baseline and following the routine 3 months treatment escalation to provide the potential for some participants to recover. We were therefore able to monitor changes in brain neurochemistry as clinical characteristics potentially changed over time.ResultsThe results, from 18 participants who completed both baseline and follow-up measures, demonstrated that improvements in migraine frequency, intensity and disability were associated with an increase in GABA+ levels in the anterior cingulate cortex (ACC); migraine frequency (r = − 0.51, p = 0.03), intensity (r = − 0.51, p = 0.03) and disability (r = − 0.53, p = 0.02). However, this was not seen in the posterior cingulate gyrus (PCG). An incidental observation found those who happened to have their treatment escalated with CGRP-monoclonal antibodies (CGRP-mAbs) (n = 10) had a greater increase in ACC GABA+ levels (mean difference 0.54 IU IQR [0.02 to 1.05], p = 0.05) and reduction in migraine frequency (mean difference 10.3 IQR [2.52 to 18.07], p = 0.01) compared to those who did not (n = 8).ConclusionThe correlation between an increase in ACC GABA+ levels with improvement in clinical characteristics of migraine, suggest previously reported elevated GABA+ levels may not be a cause of migraine, but a protective mechanism attempting to suppress further migraine attacks.

Biomarkers in PTSD-susceptible and resistant veterans with war experience of more than ten years ago: FOCUS ON cortisol, thyroid hormones, testosterone and GABA

In the present study we measured the concentrations of cortisol, thyroid hormones, testosterone, and GABA (gamma aminobutyric acid) in am blood plasma samples of combatants with an at least 10 year history of military psychological trauma (N = 74) divided in groups that either suffer from post-traumatic stress disorder (PTSD) (N = 37) or are resistant (N = 37) as well as in a control group without traumatic experience in the anamnesis, (N = 34). PTSD symptoms were assessed using the Clinician-Administered PTSD Scale (CAPS).The results show that the am blood cortisol levels of individuals that were exposed to war zone experiences irrespective susceptibility for or resistance to PTSD were significantly higher than the values observed in the controls. Testosterone levels in PTSD patients differed neither from that observed in PTSD resistant nor control groups. In the resistant group testosterone levels were however significantly higher than in controls. The level of all thyroid hormones did not differ between the study groups. GABA level was significantly lower in the PTSD group compared with healthy controls. In the resistant group blood GABA levels were not significantly different from either PTSD patients or controls.In conclusion, the current data show that cortisol and to some extent testosterone may serve as biomarker of war zone stress per se, even if trauma was experienced at least ten years before, rather than of only PTSD or resistance to PTSD. GABA, in contrast, can be considered a potential marker of the protracted nature of PTSD.

Клініко-неврологічні особливості та вміст нейроамінокислот у хворих із фармакорезистентними лицьовими симпаталгіями

Нами було обстежено 56 хворих із фармакорезистентними лицьовими симпаталгіями різного ступеня вираженості больового синдрому, в сироватці крові яких спектрофотометричним методом визначено базовий вміст глутамату, аспартату та гамма-аміномасляної кислоти для вивчення їх впливу на формування і вираженість больового синдрому. В даній роботі показано, що у хворих із фармакорезистентними лицьовими симпаталгіями з найбільш вираженим больовим синдромом відзначається найбільш значущі зміни вмісту нейроамінокислот, а саме зростання рівня глутамату, зменшення рівня гальмівних амінокислот, зокрема гамма-аміномасляної кислоти, при порівнянні з контролем, що свідчить про неефективність гальмівних механізмів у даної категорії пацієнтів. Необхідним є подальше вивчення особливостей нейроамінокислотного дисбалансу у хворих із фармакорезистентними лицьовими симпаталгіями для розробки диференціально-діагностичних і прогностичних критеріїв перебігу та нових шляхів лікування.

Lactobacillus plantarum DP189 prevents cognitive dysfunction in D-galactose/AlCl3 induced mouse model of Alzheimer’s disease via modulating gut microbiota and PI3K/Akt/GSK-3β signaling pathway

ABSTRACT Probiotic intervention has beneficial effects on host brain function and behavior via regulating microbiota-gut-brain axis; however, the underlying mechanism is not yet understood. Herein, we investigated that the effects of Lactobacillus plantarum DP189 (DP189) administration in preventing cognitive dysfunction and pathology of Alzheimer’s disease (AD) in D-galactose (D-gal) and AlCl3-induced AD model mice. After L. plantarum DP189 intervention for 10 weeks, we assessed cognitive behavior, neurotransmitter expression, histological changes, microbial communities, and the mechanisms underlying the disease in AD model mice. The results showed that L. plantarum DP189 intervention prevented cognitive dysfunction by behavioral test. Increased levels of serotonin, dopamine, and gamma-aminobutyric acid positively affected the pathological processes by ameliorating neuronal damage, beta-amyloid deposition, and tau pathology. L. plantarum DP189 intervention simultaneously modulated the gut microbial communities to alleviate gut dysbiosis. Moreover, L. plantarum DP189 inhibited tau hyperphosphorylation by regulating the PI3 K/Akt/GSK-3β pathway. These findings indicated that L. plantarum DP189 intervention is a promising therapeutic strategy to prevent the onset and development of AD.

Semen Sojae Praeparatum alters depression-like behaviors in chronic unpredictable mild stress rats via intestinal microbiota

A large number of Chinese medical books present that Semen Sojae Praeparatum, a fermented food, possesses antidepressant effect, but the mechanism of this antidepressant effect remains largely unknown. This study aimed to explore the effect of Semen Sojae Praeparatum on rats with chronic unpredictable mild stress (CUMS)-induced depression. The results showed that Semen Sojae Praeparatum improved depression-like behaviors (negative preference of sugar water and increased swimming immobility time and time spent in the dark zone) and effectively reduced cell morphological changes in the dentate gyrus of the hippocampus in CUMS rats. In addition, Semen Sojae Praeparatum significantly promoted the contents of norepinephrine (NE), 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), and gamma-aminobutyric acid (GABA) in the hippocampus and the content of BDNF in the serum (p < 0.05). 16S rRNA sequencing analysis results showed that Semen Sojae Praeparatum increased the abundance of genus Ruminococcaceae_UCG-008 and decreased those of genera Lactobacillus and Bacteroides. Genus Ruminococcaceae_UCG-008 was positively correlated with GABA and BDNF levels in the hippocampus; genus Lactobacillus had a positive correlation with 5-HT; and genus Bacteroides had negative correlations with 5-HT, BDNF, and NE. In addition, Semen Sojae Praeparatum considerably decreased the concentration of short-chain fatty acids (SCFAs). These results indicated that Semen Sojae Praeparatum fermented by Rhizopus chinensis 12 and Bacillus sp. DU-106 alleviated the neurotransmitter levels and structural changes in the neuronal morphology of the hippocampus associated with the modulation of gut microbiota and SCFAs. Therefore, this study confirmed that Semen Sojae Praeparatum could alter depression and provide a theoretical basis for the investigation of the relationship between the microbiota–gut–brain axis and antidepressant.

Fabrication of Highly Sensitive Pt-black Electrochemical Sensors for GABA Detection.

GABA (Gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the central nervous system of mammals. It is known to be related with various neurological disorders. GABA plays a crucial role in normal neuronal activity, information processing and plasticity, and neuronal network synchronization. To date, microdialysis has been widely used to monitor the level of GABA but the temporal and spatial resolution is limited. Besides, electrochemical sensors for neurotransmitter measurement, having high temporal and spatial resolution, overcome this problem. Here, using a cost-effective method of electrodeposition of platinum black (Pt-black), a highly sensitive, GABA specific, amperometric electrochemical sensor is fabricated. Nanostructured Pt-black increases the active surface area of the electrode contributing to higher sensitivity. Along with that, a self-referencing site and an exclusion layer are integrated to increase the selectivity and the signal-to-noise ratio (SNR) of the biosensor. This provides a prototype for a highly sensitive GABA sensor that could later be used to study various neurological disorders related to GABA concentrations.Clinical Relevance- This electrochemical sensor allows real-time monitoring of major inhibitory neurotransmitter (GABA) with high sensitivity which can be used for studying various neurological disorders.

Inhibition of monoamine oxidase B prevents reactive astrogliosis and scar formation in stab wound injury model.

Reactive astrocytes manifest molecular, structural, and functional alterations under various pathological conditions. We have previously demonstrated that the reactive astrocytes of the stab wound injury model (STAB) display aberrant cellular gamma-aminobutyric acid (GABA) content and tonic GABA release, whereas the active astrocytes under enriched environment (EE) express high levels of proBDNF. However, the role of monoamine oxidase B (MAO-B) in reactive astrogliosis and hypertrophy still remains unknown. Here, we investigate the role of MAO-B, a GABA-producing enzyme, in reactive astrogliosis in STAB. We observed that the genetic removal of MAO-B significantly reduced the hypertrophy, scar formation, and GABA production of reactive astrocytes, whereas the MAO-B overexpression under glial fibrillary acidic protein (GFAP) promoter enhanced the levels of GFAP and GABA. Furthermore, we found that one of the by-products of the MAO-B action, H2 O2 , but not GABA, was sufficient and necessary for the hypertrophy of reactive astrocytes. Notably, we identified two potent pharmacological tools to attenuate scar-forming astrogliosis-the recently developed reversible MAO-B inhibitor, KDS2010, and an H2 O2 scavenger, crisdesalazine (AAD-2004). Our results implicate that inhibiting MAO-B activity has dual beneficial effects in preventing astrogliosis and scar-formation under brain injury, and that the MAO-B/H2 O2 pathway can be a useful therapeutic target with a high clinical potential.

Performance, Carcass Yield, Muscle Amino Acid Profile, and Levels of Brain Neurotransmitters in Aged Laying Hens Fed Diets Supplemented with Guanidinoacetic Acid.

Simple SummaryIn commercial laying hens, aging is associated with a lower egg production rate and the marketing of spent hen carcasses shows some difficulty, probably due to the expected low meat yield. Using these hens as whole carcasses or to produce meat products for large-scale consumption could provide economic benefits to the poultry markets in developing countries. Thus, the aim of this study was to investigate the effect of dietary supplementation with guanidinoacetic acid (GA) on the carcass yield and muscle amino acid profile of aged laying hens. Dietary GA supplements were shown to improve the carcass yield and the levels of essential amino acids in the breast and thigh muscles of laying hens.Guanidinoacetic acid (GA) is a natural precursor of creatine in the body and is usually used to improve the feed conversion and cellular energy metabolism of broiler chickens. The objective was to elucidate the effect of dietary supplementation of GA on carcass yield, muscle amino acid profile, and concentrations of brain neurotransmitters in laying hens. In total, 128 72-week-old ISA Brown laying hens were assigned to four equal groups (32 birds, eight replicates per group). The control group (T1) was fed a basal diet with no supplements, while the other experimental groups were fed a basal diet supplemented with 0.5 (T2), 1.0 (T3), and 1.5 (T4) g GA kg−1 diet. The T3 and T4 groups showed higher hen-day egg production and carcass yield compared to the control group (p = 0.016 and 0.039, respectively). The serum creatine level increased linearly with the increased level of dietary GA (p = 0.007). Among the essential amino acids of breast muscle, a GA-supplemented diet linearly increased the levels of leucine, isoleucine, phenylalanine, methionine, and threonine in the breast (p = 0.003, 0.047, 0.001, 0.001, and 0.015, respectively) and thigh (p = 0.026, 0.001, 0.020, 0.009, and 0.028, respectively) muscles. GA supplementation linearly reduced the level of brain serotonin compared to the control group (p = 0.010). Furthermore, supplementation of GA in the diet of laying hens linearly increased the level of brain dopamine (p = 0.011), but reduced the level of brain Gamma-aminobutyric acid (p = 0.027). Meanwhile, the concentration of brain nitric oxide did not differ between the experimental groups (p = 0.080). In conclusion, the dietary supplementation of GA may improve the carcass yield and levels of essential amino acids in the breast muscles, as well as the brain neurotransmitters in aged laying hens.

Distribution and daily oscillation of GABA in the circadian system of the cockroach Rhyparobia maderae.

Gamma-aminobutyric acid (GABA) is the prevalent inhibitory neurotransmitter in nervous systems promoting sleep in both mammals and insects. In the Madeira cockroach, sleep-wake cycles are controlled by a circadian clock network in the brain's optic lobes, centered in the accessory medulla (AME) with its innervating pigment-dispersing factor (PDF) expressing clock neurons at the anterior-ventral rim of the medulla. GABA is present in cell clusters that innervate different circuits of the cockroach's AME clock, without colocalizing in PDF clock neurons. Physiological, immunohistochemical, and behavioral assays provided evidence for a role of GABA in light entrainment, possibly via the distal tract that connects the AME's glomeruli to the medulla. Furthermore, GABA was implemented in clock outputs to multiple effector systems in optic lobe and midbrain. Here, GABAergic brain circuits were analyzed further, focusing on the circadian system in search for sleep/wake controlling brain circuits. All GABA-immunoreactive neurons of the cockroach brain were also stained with an antiserum against the GABA-synthesizing enzyme glutamic acid decarboxylase. We found strong overlap of the distribution of GABA-immunoreactive networks with PDF clock networks in optic lobes and midbrain. Neurons in five of the six soma groups that innervate the clock exhibited GABA immunoreactivity. The intensity of GABA immunoreactivity in the distal tract showed daily fluctuations with maximum staining intensity in the middle of the day and weakest staining at the end of the day. Quantification via enzyme-linked immunosorbent assay and quantitative liquid chromatography coupled to electrospray ionization tandem mass spectrometry, likewise, showed higher GABA levels in the optic lobe during the inactivity phase of the cockroach during the day and lower levels during its activity phase at dusk. Our data further support the hypothesis that light- and PDF-dependently the circadian clock network of the cockroach controls GABA levels and thereby promotes sleep during the day.

Glutamatergic and GABAergic metabolite levels in schizophrenia-spectrum disorders: a meta-analysis of 1H-magnetic resonance spectroscopy studies.

The glutamate (Glu) and gamma aminobutyric acid (GABA) hypotheses of schizophrenia were proposed in the 1980s. However, current findings on those metabolite levels in schizophrenia have been inconsistent, and the relationship between their abnormalities and the pathophysiology of schizophrenia remains unclear. To summarize the nature of the alterations of glutamatergic and GABAergic systems in schizophrenia, we conducted meta-analyses of proton magnetic resonance spectroscopy (1H-MRS) studies examining these metabolite levels. A systematic literature search was conducted using Embase, Medline, PsycINFO, and PubMed. Original studies that compared four metabolite levels (Glu, glutamine [Gln], Glx [Glu+Gln], and GABA), as measured by 1H-MRS, between individuals at high risk for psychosis, patients with first-episode psychosis, or patients with schizophrenia and healthy controls (HC) were included. A random-effects model was used to calculate the effect sizes for group differences in these metabolite levels of 18 regions of interest between the whole group or schizophrenia group and HC. Subgroup analysis and meta-regression were performed based on the status of antipsychotic treatment, illness stage, treatment resistance, and magnetic field strength. One-hundred-thirty-four studies met the eligibility criteria, totaling 7993 participants with SZ-spectrum disorders and 8744 HC. 14 out of 18 ROIs had enough numbers of studies to examine the group difference in the metabolite levels. In the whole group, Glx levels in the basal ganglia (g = 0.32; 95% CIs: 0.18-0.45) were elevated. Subgroup analyses showed elevated Glx levels in the hippocampus (g = 0.47; 95% CIs: 0.21-0.73) and dorsolateral prefrontal cortex (g = 0.25; 95% CIs: 0.05-0.44) in unmedicated patients than HC. GABA levels in the MCC were decreased in the first-episode psychosis group compared with HC (g = -0.40; 95% CIs: -0.62 to -0.17). Treatment-resistant schizophrenia (TRS) group had elevated Glx and Glu levels in the MCC (Glx: g = 0.7; 95% CIs: 0.38-1.01; Glu: g = 0.63; 95% CIs: 0.31-0.94) while MCC Glu levels were decreased in the patient group except TRS (g = -0.17; 95% CIs: -0.33 to -0.01). Increased glutamatergic metabolite levels and reduced GABA levels indicate that the disruption of excitatory/inhibitory balance may be related to the pathophysiology of schizophrenia-spectrum disorders.

Relationships between frontal metabolites and Alzheimer's disease biomarkers in cognitively normal older adults

Elevated expression of β-amyloid (Aβ1-42) and tau are considered risk-factors for Alzheimer's disease in healthy older adults. We investigated the effect of aging and cerebrospinal fluid levels of Aβ1-42 and tau on 1) frontal metabolites measured with proton magnetic resonance spectroscopy (MRS) and 2) cognition in cognitively normal older adults (n = 144; age range 50-85). Levels of frontal gamma aminobutyric acid (GABA+) and myo-inositol relative to creatine (mI/tCr) were predicted by age. Levels of GABA+ predicted cognitive performance better than mI/tCr. Additionally, we found that frontal levels of n-acetylaspartate relative to creatine (tNAA/tCr) were predicted by levels of t-tau. In cognitively normal older adults, levels of frontal GABA+ and mI/tCr are predicted by aging, with levels of GABA+ decreasing with age and the opposite for mI/tCr. These results suggest that age- and biomarker-related changes in brain metabolites are not only located in the posterior cortex as suggested by previous studies and further demonstrate that MRS is a viable tool in the study of aging and biomarkers associated with pathological aging and Alzheimer's disease.

A role for GABA in the modulation of striatal and hippocampal systems under stress

Previous research has demonstrated that stress modulates the competitive interaction between the hippocampus and striatum, two structures known to be critically involved in motor sequence learning. These earlier investigations, however, have largely focused on blood oxygen-level dependent (BOLD) responses. No study to date has examined the link between stress, motor learning and levels of striatal and hippocampal gamma-aminobutyric acid (GABA). This knowledge gap is surprising given the known role of GABA in neuroplasticity subserving learning and memory. The current study thus examined: a) the effects of motor learning and stress on striatal and hippocampal GABA levels; and b) how learning- and stress-induced changes in GABA relate to the neural correlates of learning. To do so, fifty-three healthy young adults were exposed to a stressful or non-stressful control intervention before motor sequence learning. Striatal and hippocampal GABA levels were assessed at baseline and post-intervention/learning using magnetic resonance spectroscopy. Regression analyses indicated that stress modulated the link between striatal GABA levels and functional plasticity in both the hippocampus and striatum during learning as measured with fMRI. This study provides evidence for a role of GABA in the stress-induced modulation of striatal and hippocampal systems.

Investigating the Effects of Allium sativum on the Prefrontal Cortex in Lithium Chloride Pilocarpine-Induced Epilepsy in Wistar Rat

The prefrontal cortex (PFC), mediating executive brain functions is impaired in epilepsy. Allium sativum (AS) anti-seizure potential on the PFC of experimentally-induced epilepsy was investigated. Forty-eight male Wistar rats (200-250g) were randomized into six groups. Control (2mL/kg distilled water); AS only (100mg/kg); LiCl+PC (lithium chloride, 127mg/kg, and pilocarpine, 30mg/kg); LiCl+PC+AS100mg/kg and LiCl+PC+AS300mg/kg received LiCl+PC and 100mg/kg AS and 300mg/kg AS respectively; LiCl+PC+SV received LiCl+PC and sodium valproate (10mg/kg). Treatments lasted for 21 days, behavioural tests then preceded sacrifice. Brain tissues were excised, fixed in 10% neutral buffered formalin for demonstration of PFC cytoarchitecture and glial fibrillary acidic protein (GFAP) expression. Neurotransmitters were also assayed. Walling and rearing frequencies reduced significantly (p&lt;0.05) in the LiCl+PC group compared to control. Glutamate and acetylcholine levels increased in all groups except AS only, while gamma-aminobutyric acid, dopamine, serotonin and norepinephrine levels increased in the LiCl+PC+AS100mg/kg, LiCl+PC+AS300mg/kg and LiCl+PC+SV groups compared to the control. Cytochrome C oxidase and glucose-6-phosphate dehydrogenase activities significantly increased (p&lt;0.05) in all groups, while nitric oxide levels increased in the LiCl+PC+AS300mg/kg and LiCl+PC+SV groups compared to the control. Cytoarchitecturally, the LiCl+PC PFC showed neurodegenerative features, increased GFAP expression, while the treated groups showed preserved neurons and mild astrogliosis. Conclusively, AS showed neuroprotective potentials against LiCl+PC-induced neuronal degeneration, mitigated reactive PFC astrogliosis. However, AS did not lower glutamate and other neurotransmitter levels.

Results from a randomized, double-blind, placebo-controlled, crossover, multimodal-MRI pilot study of gabapentin for co-occurring bipolar and cannabis use disorders.

Disrupted brain gamma-aminobutyric acid (GABA)/glutamate homeostasis is a promising target for pharmacological intervention in co-occurring bipolar disorder (BD) and cannabis use disorder (CUD). Gabapentin is a safe and well-tolerated medication, FDA-approved to treat other neurological diseases, that restores GABA/glutamate homeostasis, with treatment studies supporting efficacy in treating CUD, as well as anxiety and sleep disorders that are common to both BD and CUD. The present manuscript represents the primary report of a randomized, double-blind, placebo-controlled, crossover (1-week/condition), multimodal-MRI (proton-MR spectroscopy, functional MRI) pilot study of gabapentin (1200 mg/day) in BD + CUD (n= 22). Primary analyses revealed that (1) gabapentin was well tolerated and adherence and retention were high, (2) gabapentin increased dorsal anterior cingulate cortex (dACC) and right basal ganglia (rBG) glutamate levels and (3) gabapentin increased activation to visual cannabis cues in the posterior midcingulate cortex (pMCC, a region involved in response inhibition to rewarding stimuli). Exploratory evaluation of clinical outcomes further found that in participants taking gabapentin versus placebo, (1) elevations of dACC GABA levels were associated with lower manic/mixed and depressive symptoms and (2) elevations of rBG glutamate levels and pMCC activation to cannabis cues were associated with lower cannabis use. Though promising, the findings from this study should be interpreted with caution due to observed randomization order effects on dACC glutamate levels and identification of statistical moderators that differed by randomization order (i.e. cigarette-smoking status on rBG glutamate levels and pMCC cue activation). Nonetheless, they provide the necessary foundation for a more robustly designed (urn-randomized, parallel-group) future study of adjuvant gabapentin for BD + CUD.

Dietary gamma-aminobutyric acid (GABA) supplementation increases food intake, influences the expression of feeding-related genes and improves digestion and growth of Chinese mitten crab (Eriocheir sinensis)

Animal growth performance is determined by food intake, digestion and nutrient absorption and the complex central and peripheral nerves may regulate the quantity of food intake. This study evaluates the effects of gamma-aminobutyric acid (GABA) supplements in purified diets on the growth performance, food intake and digestive ability of juvenile Chinese mitten crab Eriocheir sinensis, and the possible mechanism of neuromodulation. A total of 1200 juvenile crabs (0.77 ± 0.02 g) were fed with six diets supplemented with graded GABA levels (0, 40, 80, 160, 320 and 640 mg/kg dry matter) for 8 weeks. Each diet group had five replicates, and each replicate had 40 crabs in a tank (100 × 80 × 60 cm). The weight gain, specific growth rate, molting frequency, and the activities of digestion (α-amylase, trypsin and lipase) and absorption (Na+-K+-ATPase and γ- glutamyl transferase) enzymes were significantly increased by moderate dietary GABA supplementation compared with the 0 mg/kg GABA supplementation group. Furthermore, the food intake of juvenile E. sinensis was significantly increased with moderate dietary GABA supplementation compared with the 0 mg/kg GABA supplementation group. The qRT-PCR results showed that the expression of the orexigenic neural signal-related genes was significantly up-regulated, and the anorexigenic neural signal-related genes were significantly down-regulated in the cranial ganglia, thoracic ganglia and intestine tissues. Meanwhile, the expressions of the main genes involved in taste modulation and reward regulation were significantly up-regulated, whereas the expression of genes related to punishment regulation was significantly down-regulated in cranial ganglia and thoracic ganglia. Two-slope broken-line regression analysis of specific growth rate and weight gain against the dietary GABA levels showed that dietary GABA at the optimal dietary level was 84–89 mg/kg, and this level can improve growth performance, food intake, digestion and absorption in juvenile E. sinensis. GABA might act as an orexigenic neural signal or work with other appetite-related nerve signals to promote food intake by participating in regulating the satiety circuit and the reward circuit.

Impact of parboiling and cultivars on the free and total amino acid composition of rice ( Oryza sativa L.)

Parboiling imparts significant changes to nutritional composition of rice. The study presents the variations in amino acid (AA) composition of rice observed during parboiling process, observed in selected Sri Lankan rice cultivars. Upon parboiling, the change in levels of free and protein bound amino acids inconsistently varied across the rice cultivars and upon the parboiling technique. In comparison to non-parboiled rice, parboiling resulted in pronounced increase in nutritional gamma amino butyric acid (GABA) levels ranging from 2 times up to 11 times rendering parboiled rice a functional food. Rice parboiled after soaking for 48 hr using steam reported the highest free AA and GABA contents, while parboiling with steeping in boiling water after 24 hr soaking accounted for higher total amino acid contents in rice. Hence, for production of parboiled rice with increased nutritive value in respect of AA levels, the significance of optimization of post-processing conditions in parboiling is highlighted. Novelty impact statement Parboiling is a post harvesting technique which improves the cooking, storage, and nutritional quality of rice. In the approach to investigate the variations in amino acid composition of rice upon parboiling, the present study discusses the significant impact caused by the cultivar and the technique being used on the amino acid composition. Hence, an insight is provided into the utilization of optimum conditions during the parboiling process to produce parboiled rice enriched with high amino acid levels including gamma amino butyric acid.

Ventromedial prefrontal cortex/anterior cingulate cortex Glx, glutamate, and GABA levels in medication-free major depressive disorder

Glutamate (Glu) and gamma-aminobutyric acid (GABA) are implicated in the pathophysiology of major depressive disorder (MDD). GABA levels or GABAergic interneuron numbers are generally low in MDD, potentially disinhibiting Glu release. It is unclear whether Glu release or turnover is increased in depression. Conversely, a meta-analysis of prefrontal proton magnetic resonance spectroscopy (1H MRS) studies in MDD finds low Glx (combination of glutamate and glutamine) in medicated MDD. We hypothesize that elevated Glx or Glu may be a marker of more severe, untreated MDD. We examined ventromedial prefrontal cortex/anterior cingulate cortex (vmPFC/ACC) Glx and glutamate levels using 1H MRS in 34 medication-free, symptomatic, chronically ill MDD patients and 32 healthy volunteers, and GABA levels in a subsample. Elevated Glx and Glu were observed in MDD compared with healthy volunteers, with the highest levels seen in males with MDD. vmPFC/ACC GABA was low in MDD. Higher Glx levels correlated with more severe depression and lower GABA. MDD severity and diagnosis were both linked to higher Glx in vmPFC/ACC. Low GABA in a subset of these patients is consistent with our hypothesized model of low GABA leading to glutamate disinhibition in MDD. This finding and model are consistent with our previously reported findings that the NMDAR-antagonist antidepressant effect is proportional to the reduction of vmPFC/ACC Glx or Glu levels.