Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairme...Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.展开更多
BACKGROUND Depression is a prevalent affective disorder,but its pathophysiology remains unclear.Dysfunction in the gamma-aminobutyric acid(GABA)-ergic system may contribute to its onset.Recently,antidepressants(e.g.,b...BACKGROUND Depression is a prevalent affective disorder,but its pathophysiology remains unclear.Dysfunction in the gamma-aminobutyric acid(GABA)-ergic system may contribute to its onset.Recently,antidepressants(e.g.,brexanolone,zuranolone)targeting the GABA-A receptor were introduced.The zona incerta(ZI),an inhibitory subthalamic region mainly composed of GABAergic neurons,has been implicated in emotional regulation.Deep brain stimulation of the ZI in humans affects anxiety and depression symptoms,while activation of ZI neurons in mice can either worsen or alleviate anxiety.Currently,there is no direct evidence linking GABAergic neurons in the ZI to depression-like behaviors in rodents.AIM To explore the relationship between GABAergic neurons in the ZI and depression-like behaviors in mice.METHODS A chronic restraint stress(CRS)model was utilized to induce depression in mice.Whole-cell patch-clamp recordings assessed the excitability changes of GABAergic neurons in the ZI.Additionally,chemogenetic techniques were employed to modulate ZI GABAergic neurons.The performance of the mice in behavioral tests for depression and anxiety was observed.RESULTS The findings indicated that GABAergic neurons in the ZI were closely associated with depression-like behaviors in mice.Twenty-eight days after the CRS model was established,depression-like and anxiety-like behaviors were observed in the mice.The excitability of GABAergic neurons in the ZI was reduced.Chemogenetic activation of these neurons alleviated CRS-induced depression-like and anxiety-like behaviors.Conversely,inhibition of GABAergic neurons in the ZI led to changes in emotion-related behavioral outcomes in mice.CONCLUSION Activity of GABAergic neurons in the ZI was closely associated with depression-like phenotypes in mice,suggesting that these neurons could be a potential therapeutic target for treating depression.展开更多
AIM:To investigate the postnatal development of parvalbumin(PV)-positive gamma-aminobutyric acid(GABA)interneurons and the co-expression of perineuronal nets(PNNs)and PV in the visual cortex of rats,as well as the reg...AIM:To investigate the postnatal development of parvalbumin(PV)-positive gamma-aminobutyric acid(GABA)interneurons and the co-expression of perineuronal nets(PNNs)and PV in the visual cortex of rats,as well as the regulatory effects of fluoxetine(FLX)treatment and binocular form deprivation(BFD)on these indices.METHODS:Wistar rats were assigned to three experimental cohorts:1)Age-related groups:postnatal week(PW)1,PW3,PW5,PW7,and PW9;2)FLX treatment duration groups:FLX 0W,FLX 2W,FLX 4W,FLX 6W,and FLX 8W;3)Intervention groups:control(Cont),FLX,BFD,and BFD+FLX.The levels of PNNs,PV,and PNNs/PV coexpression in the visual cortex were detected and analyzed.RESULTS:The density of PV-positive cells and the coexpression of PNNs and PV increased gradually with the maturation of the visual cortex(b=0.960,P<0.01).The ratio of PV-positive cells surrounded by PNNs to total PV-positive cells(PNNs+/PV+/total PV+)was significantly decreased in the FLX 4W group(χ^(2)=9.03,P=0.003).There was no significant difference in the PNNs+/PV+/total PV+ratio between the FLX and BFD groups(χ^(2)=1.08,P=0.161),but a significant difference was observed between the BFD+FLX group and the BFD group(χ^(2)=5.82,P<0.01).CONCLUSION:The number of PV-positive neurons and PNNs-surrounded PV neurons in the rat visual cortex increases postnatally and reaches adult levels by postnatal week 7.Chronic FLX treatment downregulates these expressions.Combined 4-week FLX treatment and BFD exerts a more significant inhibitory effect on the PNNs+/PV+/total PV+ratio than either intervention alone.展开更多
AIM:To investigate the expression pattern of gamma-aminobutyric acid A(GABAA) receptors in hepatocellular carcinoma(HCC) and indicate the relationship among gamma-aminobutyric acid(GABA),gamma-aminobutyric acid A rece...AIM:To investigate the expression pattern of gamma-aminobutyric acid A(GABAA) receptors in hepatocellular carcinoma(HCC) and indicate the relationship among gamma-aminobutyric acid(GABA),gamma-aminobutyric acid A receptor α3 subunit(GABRA3) and HCC.METHODS:HCC cell line Chang,HepG2,normal liver cell line L-02 and 8 samples of HCC tissues and paired non-cancerous tissues were analyzed with semiquantitative polymerase chain reaction(PCR) for the expression of GABAA receptors.HepG2 cells were treated with gamma-aminobutyric acid(GABA) at serial concentrations(0,1,10,20,40 and 60 μmol/L),and their proliferating abilities were analyzed with the 3-(4,5-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay,cell doubling time test,colon formation assay,cell cycle analysis and tumor planted in nude mice.Small interfering RNA was used for knocking down the endogenous GABRA3 in HepG2.Proliferating abilities of these cells treated with or without GABA were analyzed.RESULTS:We identified the overexpression of GABRA3 in HCC cells.Knockdown of endogenous GABRA3 expression in HepG2 attenuated HCC cell growth,suggesting its role in HCC cell viability.We determined the in vitro and in vivo effect of GABA in the proliferation of GABRA3-positive cell lines,and found that GABA increased HCC growth in a dose-dependent manner.Notably,the addition of GABA into the cell culture medium promoted the proliferation of GABRA3-expressing HepG2 cells,but not GABRA3-knockdown HepG2 cells.This means that GABA stimulates HepG2 cell growth through GABRA3.CONCLUSION:GABA and GABRA3 play important roles in HCC development and progression and can be a promising molecular target for the development of new diagnostic and therapeutic strategies for HCC.展开更多
Methods to optimize the production of gamma-aminobutyric acid （GABA） by Lactobacillus brevis CGMCC 1306 were investigated. Results indicated that cell growth was maximal at pH 5.0, while pH 4.5 was pref-erable to GA...Methods to optimize the production of gamma-aminobutyric acid （GABA） by Lactobacillus brevis CGMCC 1306 were investigated. Results indicated that cell growth was maximal at pH 5.0, while pH 4.5 was pref-erable to GABA formation. The optimal temperature for cell growth （35 °C） was lower than that for GABA forma-tion （40 °C）. In a two-stage pH and temperature control fermentation, cultures were maintained at pH 5.0 and 35 °C for 32 h, then adjusted to pH 4.5 and 40 °C, GABA production increased remarkably and reached 474.79 mmol·L-1 at 72 h, while it was 398.63 mmol·L-1 with one stage pH and temperature control process, in which cultivation con-ditions were constantly controlled at pH 5.0 and 35 °C. In order to avoid the inhibition of cell growth at higher L-monosodium glutamate （L-MSG） concentrations, the two-stage control fermentation with substrate feeding strat-egy was applied to GABA production, with 106.87 mmol （20 g） L-MSG supplemented into the shaking-flask at 32 h and 56 h post-inoculation separately. The GABA concentration reached 526.33 mmol·L-1 at 72 h with the fer-mentation volume increased by 38%. These results will provide primary data to realize large-scale production of GABA by L. brevis CGMCC 1306.展开更多
Gamma-aminobutyric acid(GABA)and glutamate are two important amino acid neurotransmitters widely present in the nervous systems of mammals,insects,round worm,and platyhelminths,while their receptors are quite diversif...Gamma-aminobutyric acid(GABA)and glutamate are two important amino acid neurotransmitters widely present in the nervous systems of mammals,insects,round worm,and platyhelminths,while their receptors are quite diversified across different animal phyla.However,the evolutionary mechanisms between the two conserved neurotransmitters and their diversified receptors remain elusive,and antagonistic interactions between GABA and glutamate signal transduction systems,in particular,have begun to attract significant attention.In this review,we summarize the extant results on the origin and evolution of GABA and glutamate,as well as their receptors,and analyze possible evolutionary processes and phylogenetic relationships of various GABAs and glutamate receptors.We further discuss the evolutionary history of Excitatory/Neutral Amino Acid Transporter(EAAT),a transport protein,which plays an important role in the GABA-glutamate“yin and yang”balanced regulation.Finally,based on current advances,we propose several potential directions of future research.展开更多
Alzheimer＇s disease （AD）, the predominant form of dementia, is a chronic, incurable neurodegenerative disorder presenting with symptoms includ- ing progressive memory loss and disturbed emotional state. It has been...Alzheimer＇s disease （AD）, the predominant form of dementia, is a chronic, incurable neurodegenerative disorder presenting with symptoms includ- ing progressive memory loss and disturbed emotional state. It has been estimated that dementia affects over 47 million people worldwide （Prince et al., 2015）, and with 60-80% of cases attributable to AD.展开更多
BACKGROUND： Gamma-aminobutyric acid transporter plays an important role in gamma-aminobutyric acid metabolism, and is highly associated with epilepsy seizures. Pathologically, astrocytes release active substances tha...BACKGROUND： Gamma-aminobutyric acid transporter plays an important role in gamma-aminobutyric acid metabolism, and is highly associated with epilepsy seizures. Pathologically, astrocytes release active substances that alter neuronal excitability, and it has been demonstrated that astrocytes play a role in epileptic seizures. OBJECTIVE： To observe changes in gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression in the hippocampus and cortex of the temporal lobe in rats with pentylenetetrazol-induced chronic epilepsy. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment was performed at the Department of Neurobiology, Third Military University of Chinese PLA between January 2006 and December 2007. MATERIALS： Pentylenetetrazol was purchased from Sigma, USA; rabbit anti-rat gammaaminobutyric acid transporter 1 and glial fibrillary acidic protein were from Chemicon, USA. METHODS： A total of 40 Sprague Dawley rats were divided into model and control groups. Rat models of chronic epilepsy were created by pentylenetetrazol kindling, and were subdivided into 3-, 7-, and 14-day kindling subgroups. MAIN OUTCOME MEASURES： Gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression, as well as the number of positive cells in the hippocampus and cortex of temporal lobe of rats, were determined by immunohistochemistry and Western blot analyses. RESULTS： Compared with the control group, the number of gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein -positive cells in the hippocampus and cortex of rats with pentylenetetrazol-induced epilepsy significantly increased, gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression increased after 3 days of kindling, reached a peak on day 7, and remained at elevated levels at day 14 （P〈 0.05）. CONCLUSION： Astrocytic activation and gamma-aminobutyric acid transporter 1 overexpression may contribute to pentylenetetrazol-induced epilepsy.展开更多
[ Objective] To study the effects of gamma-aminobutyric acid （GABA） on performance of lactating sows during heat stress. [ Metbod] A total of 14 sows at the same parity and with close expected date of childbirth and...[ Objective] To study the effects of gamma-aminobutyric acid （GABA） on performance of lactating sows during heat stress. [ Metbod] A total of 14 sows at the same parity and with close expected date of childbirth and similar body we：,ght were randomly divided into control group and experimental group. They were fed a common basal diet and a GABA （300 mg/kg） supplementary diet, respectively. The trial lasted for 21 d. [ Result ] The daily feed intake, lactation yield and average daily gain of piglets in the experimental group were increased by 9.4%, 28.5% and 10.7%, respectively. The backfat of lactating sows was decreased less, and the same with the weaning-oestrus interval. The survival ratio of piglets was increased by 4.5%. Compared with the control group, the content of lactose and fat increased significantly, but other components almost did not change. [Conclusien] Supplementing GABA in diet can improve the performance of lactating sows and promote the growth of piglets effectively.展开更多
BACKGROUND： Gamma-aminobutyric acid A （GABAA） and N-methyl-D-aspartate （NMDA） receptors are significant receptors in the central nervous system. An understanding of GABAA and NMDA receptor expression in spiral ga...BACKGROUND： Gamma-aminobutyric acid A （GABAA） and N-methyl-D-aspartate （NMDA） receptors are significant receptors in the central nervous system. An understanding of GABAA and NMDA receptor expression in spiral ganglion neurons （SGN） provides information for the functional role of these receptors in the auditory system. OBJECTIVE： To investigate mRNA expression of GABAA receptor （GABAAR） and NMDA receptor （NMDAR） subunits in the rat SGN. DESIGN, TIME AND SETTING： This in vitro, molecular biological study was performed at the Laboratory of Otolaryngology-Head and Neck Surgery, Guangxi Medical University, China from July 2007 to May 2008. MATERIALS： Reverse Transcriptase Kit and Taq DNA polymerase were purchased from Fermentas Burlington, ON, Canada; GABAAR and NMDAR primers were purchased from Shanghai Sangon, Shanghai, China. METHODS： SGN from 3-5 day postnatal Wistar rats was collected for primary cultures, mRNA expression of GABAAR and NMDAR subunits in the SGN was determined by reverse transcription polymerase chain reaction. MAIN OUTCOME MEASURES： Expression levels of GABAAR and NMDAR subunits were determined by quantitative analysis. RESULTS： GABAAR subunits （αl 6, β1 3, and y1 3） and NMDAR subunits （NR1, NR2A, NR2B, NR2C, NR2D, NR3A, and NR3B） were detected in the SGN. In α subunit genes of GABAAR, α1 and α3 expression was similar （P 〉 0.05） and greater than the other subunits. Of the β subunit genes, β1 subunit mRNA levels were greater than β2 and β3. Of the y subunit genes, y2 subunit mRNA levels were greater than y1 and y3. NR1 mRNA expression was the greatest of NMDAR subunits. CONCLUSION： GABAAR subunits （α1 6, β1-3, and y1-3） and NMDAR subunits （NR1, NR2A, NR2B, NR2C, NR2D, NR3A, and NR3B） were expressed in the rat SGN. Through comparison of GABAAR and NMDAR subunit expression, possible GABAAR combinations, as well as highly expressed subunit combinations, were estimated, which provided information for pharmacological and electrophysiological characteristics of GABAAR in the auditory system.展开更多
The therapeutic effect of gamma-aminobutyric acid(GABA)on diabetes was spread as one of the alarming epidemics worldwide.The study aims to investigate the function of Lactobacillus brevis KLDS_(1.0727) and KLDS_(1.037...The therapeutic effect of gamma-aminobutyric acid(GABA)on diabetes was spread as one of the alarming epidemics worldwide.The study aims to investigate the function of Lactobacillus brevis KLDS_(1.0727) and KLDS_(1.0373) strains as glutamic acid decarboxylase 65(GAD65)carriers capable of generating GABA by comparing in vitro free and freeze-dried models and GABA intervention in vivo.PCR amplification of gad and in vitro i.e.,(growth rate,viability at different pH,bile tolerance,and survivability in simulated gastric juice)were performed.In vivo experiments were conducted in 7 groups of C57BL/6J mice.Each group was injected with streptozotocin(Cont_(STZ),INSSTZ,LAC1_(STZ),LAC_(1MFDSTZ),LAC_(2STZ),LAC_(2MFDSTZ))daily except for the control(Cont).One group was injected with insulin(INSSTZ).The body weight and hyperglycemia in the blood were assessed weekly,post-euthanasia blood plasma parameters,insulin,and histological examination were evaluated.Results indicated L.brevis strains demonstrated a great tolerance to bile and simulated gastric juice in vitro(P<0.05).Cont_(STZ) had the highest average glucose level(6.84±6.46)mmol/L while INS_(STZ) expressed dramatically decreed in glucose level and displayed a significant decline in the average of weekly blood glucose(−5.74±3.08)mmol/L.The lowest body weight(ContSTZ)was(19.30±0.25)g.Based on the blood plasma analysis,L.brevis strains improved good cholesterol properties,liver and kidney functions,where most of these parameters fall within the average the reference range and prevent the development of symptoms of type 1 diabetes in vivo.As recommended,L.brevis should be commonly distributed as a postbiotic GABA in pharmaceutical and nutritional applications.展开更多
Gamma-aminobutyric acid （GABA） and glutamate are two important amino acid neurotransmitters widely present in the nervous systems of mammals, insects, round worm, and platyhelminths, while their receptors are quite ...Gamma-aminobutyric acid （GABA） and glutamate are two important amino acid neurotransmitters widely present in the nervous systems of mammals, insects, round worm, and platyhelminths, while their receptors are quite diversified across different animal phyla. However, the evolutionary mechanisms between the two conserved neurotransmitters and their diversified receptors remain elusive, and antagonistic interactions between GABA and glutamate signal transduction systems, in particular, have began to attract significant attention. In this review, we summarize the extant results on the origin and evolution of GABA and glutamate, as well as their receptors, and analyze possible evolutionary processes and phylogenetic relationships of various GABAs and glutamate receptors. We further discuss the evolutionary history of Excitatory/Neutral Amino Acid Transporter （EAAT）, a transport protein, which plays an important role in the GABA-glutamate ＂yin and yang＂ balanced regulation. Finally, based on current advances, we propose several potential directions of future research.展开更多
Gamma-aminobutyric acid(GABA)is a natural non-protein functio nal amino acid,which has potential for fermentation industrial production by Lactobacillus brevis.This work investigated the batch fermentation process and...Gamma-aminobutyric acid(GABA)is a natural non-protein functio nal amino acid,which has potential for fermentation industrial production by Lactobacillus brevis.This work investigated the batch fermentation process and developed a kinetic model based on substrate restrictive model established by experimental data from L25(5~6)orthogonal experiments.In this study,the OD600 value of fermentation broth was fixed to constant after reaching its maximum because the microorganism death showed no effect on the enzyme activity of glutamate decarboxylase(GAD).As pH is one of the key parameters in fermentation process,a pH-dependent kinetic model based on radial basis function was developed to enhance the practicality of the model.Furthermore,as to decrease the deviations between the simulated curves and the experimental data,the rolling correction strategy with OD600 values that was measured in real-time was introduced into this work to modify the model.Finally,the accu racy of the rolling corrected and pH-dependent model was validated by good fitness between the simulated curves and data of the initial batch fermentation(pH 5.2).As a result,this pH-dependent kinetic model revealed that the optimal pH for biomass growth is 5.6-5.7 and for GABA production is about 5,respectively.Therefore,the developed model is practical and convenient for the instruction of GABA fermentation production,and it has instructive significance for the industrial scale.展开更多
Glutamic acid and gamma-aminobutyric acid （GABA） influence iron content in the substantia nigra and globus pallidus, although the mechanisms of action remain unclear. The present study measured iron content and chan...Glutamic acid and gamma-aminobutyric acid （GABA） influence iron content in the substantia nigra and globus pallidus, although the mechanisms of action remain unclear. The present study measured iron content and changes in divalent metal transporter 1 （DMT1） and hephaestin expression in the substantia nigra and caudate putamen, and explored the effects of GABA and glutamic acid on iron metabolism. Results demonstrated that iron content and DMT1 non iron response element [DMT1 （-IRE）] expression were significantly greater but hephaestin expression was significantly lower in the caudate putamen of the monosodium glutamate group compared with the control group. No significant difference in iron content was detected between the GABA and control groups. DMT1 （-IRE） expression was significantly reduced, but hephaestin expressiori was significantly increased in the GABA group compared with the control group. In addition, there was no significant difference in tyrosine hydroxylase expression between monosodium glutamate and GABA groups and the control group. These results suggested that glutamate affected iron metabolism in the caudate putamen by increasing DMTI（-IRE） and decreasing hephaestin expression. In addition, GABA decreased DMT1 （-IRE） expression in the caudate putamen.展开更多
Objective:To investigate the effects of Toll-like receptor 4 antagonist Eritrane on neurogenesis and gamma-aminobutyric acid glutamate balance in the prefrontal lobe and hippocampus of depressive rats.Methods:100 heal...Objective:To investigate the effects of Toll-like receptor 4 antagonist Eritrane on neurogenesis and gamma-aminobutyric acid glutamate balance in the prefrontal lobe and hippocampus of depressive rats.Methods:100 healthy SD rats were divided into healthy control group, blank control group and Eritram group (low dose group, medium dose group and high dose group), 20 rats in each group. The depression model of rats in blank control group and Salvia miltiorrhiza group was established. After the completion of the model, rats in the blank control group were injected with normal saline and rats in the Eritrean group were injected with high, medium and low doses of Eritrean injection respectively. After 21 days of continuous administration, the total distance of spontaneous activity, the immobility time of forced swimming, the levels of gamma-aminobutyric glutamate (GABA), glutamate (Glu) and Toll-like receptor 4 (TLR-4) protein in prefrontal lobe and hippocampal neurons were measured and compared. Pearson correlation test was used to analyze the correlation between TLR4 and GABA, Glu levels in depressive rats.Results: Compared with the healthy control group, the total spontaneous activity distance of the blank control group and Eritrean group decreased significantly, and the immobility time of forced swimming increased significantly (P<0.05). There was a significant difference between the blank control group and Eritrean group (P<0.05). The rats in Eritrean group spontaneously survived with the increase of dose. The total distance increased, while the immobility time of forced swimming decreased (P<0.05). Compared with the healthy control group, the levels of GABA in the prefrontal lobe and hippocampus of rats in blank control group and Eritrean group decreased significantly, the levels of Glu and TLR4 increased significantly, and the levels of GABA in Eritrean group were higher than those in blank control group, and the levels of Glu and TLR4 were lower than those in blank control group. TLR4 and TLR4 decreased significantly (P<0.05). Pearson correlation test showed that TLR4 was negatively correlated with GABA and positively correlated with Glu (P<0.05). Conclusion: Eritrean can reduce the effects of depression on the neurogenesis of prefrontal lobe and hippocampal neurons and the balance of gamma-aminobutyric acid and glutamate in rats. The mechanism is that Eritrean can increase the level of GABA and decrease the level of Glu by antagonizing Toll-like receptor 4, thus exerting the neuroprotective effect of prefrontal lobe and hippocampal neurons.展开更多
Background Asthma is a chronic inflammatory disease characterized by reversible bronchial constriction, pulmonary inflammation and airway remodeling. Current standard therapies for asthma provide symptomatic control, ...Background Asthma is a chronic inflammatory disease characterized by reversible bronchial constriction, pulmonary inflammation and airway remodeling. Current standard therapies for asthma provide symptomatic control, but fail to target the underlying disease pathology. Furthermore, no therapeutic agent is effective in preventing airway remodeling. A substantial amount of evidence suggests that statins have anti-inflammatory properties and immunomodulatory activity. In this study, we investigated the effect of rosuvastatin on airway inflammation and its inhibitory mechanism in mucus hypersecretion in a murine model of chronic asthma. Methods BALB/c mice were sensitized and challenged by ovalbumin to induce asthma. The recruitment of inflammatory cells into bronchoalveolar lavage fluid （BALF） and the lung tissues were measured by Diff-Quik staining and hematoxylin and eosin （H＆E） staining. ELISA was used for measuring the levels of IL-4, IL-5, IL-13 and TNF-a in BALE Periodic acid-Schiff （PAS） staining was used for mucus secretion. Gamma-aminobutyric acid type A receptor （GABAAR） β2 expression was measured by means of immunohistochemistry, reverse transcription-polymerase chain reaction （RT-PCR） and Western blotting. Results Rosuvastatin reduced the number of total inflammatory cells, lymphocytes, macrophages, neutrophils, and eosinophils recruited into BALF, the levels of IL-4, IL-5, IL-13 and TNF-a in BALF, along with the histological mucus index （HMI） and GABAAR 132 expression. Changes occurred in a dose-dependent manner. Conclusions Based on its ability to reduce the inflammatory response and mucus hypersecretion by regulating GABAAR activity in a murine model of chronic asthma, rosuvastatin may be a useful therapeutic agent for treatment of asthma.展开更多
The present study was conducted to evaluate the effects of dietary gamma-aminobutyric acid(GABA)in broiler chickens raised in high stocking density(HSD)on performance and physiological responses.A total of 900 male br...The present study was conducted to evaluate the effects of dietary gamma-aminobutyric acid(GABA)in broiler chickens raised in high stocking density(HSD)on performance and physiological responses.A total of 900 male broiler chicks(Ross 308)at 1 d old were assigned in a 2×2 factorial arrangement to 4 treatments(10 replicates per treatment)with stocking density,7.5 birds/m^2(low stocking density;LSD)or 15 birds/m^2(HSD),and dietary GABA,0 or 100 mg/kg.Chickens raised in HSD exhibited a decrease in body weight gain in all phases(P<0.05)and feed intake in starter and whole phases(P<0.01),and an increase in feed conversion ratio in the finisher phase(P<0.01)compared with LSD-raised chickens.However,dietary GABA did not affect growth performance nor interacted with stocking density on production variables.The HSD vs.LSD increased relative liver weight on d 35 whereas dietary GABA increased relative liver weight and decreased relative bursa weight on d 21.Both stocking density and dietary GABA affected yield and quality of breast and leg muscles.Dietary GABA increased(P<0.05)width of tibia on d 35 and interacted(P=0.054)with stocking density on breaking stocking density on d 35.The HSD vs.LSD group lowered(P<0.05)feather coverage scores.Significant interaction between stocking density and GABA on surface temperature of shank on d 21 was noted(P=0.024).Dietary GABA exhibited an opposite effect on the concentrations of cecal short-chain fatty acids depending on stocking density leading to a moderate to significant interaction.Stocking density decreased alpha-1-acid glycoprotein whereas dietary GABA decreased heterophil-to-lymphocyte ratio and corticosterone in blood or serum samples.Serum biochemical parameters were altered by stocking density or dietary GABA.It is concluded that dietary GABA alleviated stress indices including corticosterone and heterophilto-lymphocyte ratio,but failed to reverse stocking density-induced growth depression.展开更多
Gamma-aminobutyric acid(GABA),a ubiquitous non-protein 4-carbon amino acid present in both prokaryotic and eukaryotic organisms.It is conventionally recognized as a neurotransmitter in mammals and plays a crucial role...Gamma-aminobutyric acid(GABA),a ubiquitous non-protein 4-carbon amino acid present in both prokaryotic and eukaryotic organisms.It is conventionally recognized as a neurotransmitter in mammals and plays a crucial role in plants.The context of this review centers on the impact of GABA in mitigating abiotic stresses induced by climate change,such as drought,salinity,heat,and heavy metal exposure.Beyond its neurotransmitter role,GABA emerges as a key player in diverse metabolic processes,safeguarding plants against multifaceted abiotic as well as biotic challenges.This comprehensive exploration delves into the GABA biosynthetic pathway,its transport mechanisms,and its intricate interplay with various abiotic stresses.The discussion extends to the nuanced relationship between GABA and phytohormones during abiotic stress acclimation,offering insights into the strategic development of mitigation strategies against these stresses.The delineation of GABA’s crosstalk with phytohormones underscores its pivotal role in formulating crucial strategies for abiotic stress alleviation in plants.展开更多
This study aimed to investigate the protective effect of nicotine on dopaminergic neurons and its mechanisms in mice with Parkinson disease(PD)induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).C57BL/6J mic...This study aimed to investigate the protective effect of nicotine on dopaminergic neurons and its mechanisms in mice with Parkinson disease(PD)induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).C57BL/6J mice were injected with MPTP for 8 days to establish a PD model.Nicotine was given for 10 days in the nicotine therapeutic group.Animals were examined behaviorally with the pole test and traction test.Tyrosine hydroxylase(TH)andγ-aminobutyric acid(GABA)were determined by using the immunocytochem-istry(ICC)method.The ultrastructural changes of the caudate nucleus(CN)were observed under electron microscopy.The results showed that pretreatment with nicotine could improve the dyskinesia of PD mice markedly.Simultaneously,TH-positive(P<0.01)neurons and GABA-positive(P<0.05)neurons in the nicotine therapeutic group were significantly more than those in the model group.The ultrastructural injury of the nicotine therapeutic group was also ameliorated.Nicotine has protective effects on theγ-aminobutyric acid neurons and dopaminergic neurons in the MPTP-treated mice.展开更多
Debates regarding the specific effects of general anesthesia on developing brains have persisted for over 30 years.A consensus has been reached that prolonged,repeated,high-dose exposure to anesthetics is associated w...Debates regarding the specific effects of general anesthesia on developing brains have persisted for over 30 years.A consensus has been reached that prolonged,repeated,high-dose exposure to anesthetics is associated with a higher incidence of deficits in behavior and executive function,while single exposure has a relatively minor effect on long-term neurological function.In this review,we summarize the dose-dependent neuroprotective or neurotoxic effects of gamma-aminobutyric acid type A receptor agonists,a representative group of sedatives,on developing brains or central nervous system diseases.Most preclinical research indicates that anesthetics have neurotoxic effects on the developing brain through various signal pathways.However,recent studies on low-dose anesthetics suggest that they may promote neurodevelopment during this critical period.These findings are incomprehensible for the general“dose-effect”principles of pharmacological research,which has attracted researchers'interest and led to the following questions:What is the threshold for the dual effects exerted by anesthetics such as propofol and sevoflurane on the developing brain?To what extent can their protective effects be maximized?What are the underlying mechanisms involved in these effects?Consequently,this issue has essentially become a“mathematical problem.”After summarizing the dose-dependent effects of gamma-aminobutyric acid type A receptor agonist sedatives in both the developing brain and the brains of patients with central nervous system diseases,we believe that all such anesthetics exhibit specific threshold effects unique to each drug.These effects range from neuroprotection to neurotoxicity,depending on different brain functional states.However,the exact values of the specific thresholds for different drugs in various brain states,as well as the underlying mechanisms explaining why these thresholds exist,remain unclear.Further in-depth exploration of these issues could significantly enhance the therapeutic translational value of these anesthetics.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82374561(to JD),82174490(to JF)the Medical and Health Science and Technology Program of Zhejiang Province,No.2021RC098(to JD)the Research Project of Zhejiang Chinese Medical University,Nos.2022JKZKTS44(to JD),2022FSYYZZ07(to JF).
文摘Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.
基金Supported by the Natural Science Foundation of Xiaogan,China,No.XGKJ2023010036.
文摘BACKGROUND Depression is a prevalent affective disorder,but its pathophysiology remains unclear.Dysfunction in the gamma-aminobutyric acid(GABA)-ergic system may contribute to its onset.Recently,antidepressants(e.g.,brexanolone,zuranolone)targeting the GABA-A receptor were introduced.The zona incerta(ZI),an inhibitory subthalamic region mainly composed of GABAergic neurons,has been implicated in emotional regulation.Deep brain stimulation of the ZI in humans affects anxiety and depression symptoms,while activation of ZI neurons in mice can either worsen or alleviate anxiety.Currently,there is no direct evidence linking GABAergic neurons in the ZI to depression-like behaviors in rodents.AIM To explore the relationship between GABAergic neurons in the ZI and depression-like behaviors in mice.METHODS A chronic restraint stress(CRS)model was utilized to induce depression in mice.Whole-cell patch-clamp recordings assessed the excitability changes of GABAergic neurons in the ZI.Additionally,chemogenetic techniques were employed to modulate ZI GABAergic neurons.The performance of the mice in behavioral tests for depression and anxiety was observed.RESULTS The findings indicated that GABAergic neurons in the ZI were closely associated with depression-like behaviors in mice.Twenty-eight days after the CRS model was established,depression-like and anxiety-like behaviors were observed in the mice.The excitability of GABAergic neurons in the ZI was reduced.Chemogenetic activation of these neurons alleviated CRS-induced depression-like and anxiety-like behaviors.Conversely,inhibition of GABAergic neurons in the ZI led to changes in emotion-related behavioral outcomes in mice.CONCLUSION Activity of GABAergic neurons in the ZI was closely associated with depression-like phenotypes in mice,suggesting that these neurons could be a potential therapeutic target for treating depression.
基金Supported by the Suzhou Science and Technology Bureau(No.SKY2023175)the Project of State Key Laboratory of Radiation Medicine and Protection+6 种基金Soochow University(No.GZK1202309)the Advantage Subject Lifting Project(No.XKTJ-XK202412)the Suzhou Science and Education for Strengthening Healthcare(No.MSXM2024010)the Suzhou Medical Key Supported Disciplines(No.SZFCXK202118)the Youth Scientific Research Fund Project of Kunshan Hospital of Traditional Chinese Medicine(No.2024QNJJ06)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.SJCX23_1673)the Undergraduate Training Program for Innovation and Entrepreneurship,Soochow University(No.202310285162Y).
文摘AIM:To investigate the postnatal development of parvalbumin(PV)-positive gamma-aminobutyric acid(GABA)interneurons and the co-expression of perineuronal nets(PNNs)and PV in the visual cortex of rats,as well as the regulatory effects of fluoxetine(FLX)treatment and binocular form deprivation(BFD)on these indices.METHODS:Wistar rats were assigned to three experimental cohorts:1)Age-related groups:postnatal week(PW)1,PW3,PW5,PW7,and PW9;2)FLX treatment duration groups:FLX 0W,FLX 2W,FLX 4W,FLX 6W,and FLX 8W;3)Intervention groups:control(Cont),FLX,BFD,and BFD+FLX.The levels of PNNs,PV,and PNNs/PV coexpression in the visual cortex were detected and analyzed.RESULTS:The density of PV-positive cells and the coexpression of PNNs and PV increased gradually with the maturation of the visual cortex(b=0.960,P<0.01).The ratio of PV-positive cells surrounded by PNNs to total PV-positive cells(PNNs+/PV+/total PV+)was significantly decreased in the FLX 4W group(χ^(2)=9.03,P=0.003).There was no significant difference in the PNNs+/PV+/total PV+ratio between the FLX and BFD groups(χ^(2)=1.08,P=0.161),but a significant difference was observed between the BFD+FLX group and the BFD group(χ^(2)=5.82,P<0.01).CONCLUSION:The number of PV-positive neurons and PNNs-surrounded PV neurons in the rat visual cortex increases postnatally and reaches adult levels by postnatal week 7.Chronic FLX treatment downregulates these expressions.Combined 4-week FLX treatment and BFD exerts a more significant inhibitory effect on the PNNs+/PV+/total PV+ratio than either intervention alone.
文摘AIM:To investigate the expression pattern of gamma-aminobutyric acid A(GABAA) receptors in hepatocellular carcinoma(HCC) and indicate the relationship among gamma-aminobutyric acid(GABA),gamma-aminobutyric acid A receptor α3 subunit(GABRA3) and HCC.METHODS:HCC cell line Chang,HepG2,normal liver cell line L-02 and 8 samples of HCC tissues and paired non-cancerous tissues were analyzed with semiquantitative polymerase chain reaction(PCR) for the expression of GABAA receptors.HepG2 cells were treated with gamma-aminobutyric acid(GABA) at serial concentrations(0,1,10,20,40 and 60 μmol/L),and their proliferating abilities were analyzed with the 3-(4,5-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay,cell doubling time test,colon formation assay,cell cycle analysis and tumor planted in nude mice.Small interfering RNA was used for knocking down the endogenous GABRA3 in HepG2.Proliferating abilities of these cells treated with or without GABA were analyzed.RESULTS:We identified the overexpression of GABRA3 in HCC cells.Knockdown of endogenous GABRA3 expression in HepG2 attenuated HCC cell growth,suggesting its role in HCC cell viability.We determined the in vitro and in vivo effect of GABA in the proliferation of GABRA3-positive cell lines,and found that GABA increased HCC growth in a dose-dependent manner.Notably,the addition of GABA into the cell culture medium promoted the proliferation of GABRA3-expressing HepG2 cells,but not GABRA3-knockdown HepG2 cells.This means that GABA stimulates HepG2 cell growth through GABRA3.CONCLUSION:GABA and GABRA3 play important roles in HCC development and progression and can be a promising molecular target for the development of new diagnostic and therapeutic strategies for HCC.
基金Supported by the National＇Naturai Science Foundation of China （30970638, 21176220 and 31240054）, Zhejiang Provincial Natural Science Foundation （Z13B06008） and the National Basic Research Program of China （2007CB714305）.
文摘Methods to optimize the production of gamma-aminobutyric acid （GABA） by Lactobacillus brevis CGMCC 1306 were investigated. Results indicated that cell growth was maximal at pH 5.0, while pH 4.5 was pref-erable to GABA formation. The optimal temperature for cell growth （35 °C） was lower than that for GABA forma-tion （40 °C）. In a two-stage pH and temperature control fermentation, cultures were maintained at pH 5.0 and 35 °C for 32 h, then adjusted to pH 4.5 and 40 °C, GABA production increased remarkably and reached 474.79 mmol·L-1 at 72 h, while it was 398.63 mmol·L-1 with one stage pH and temperature control process, in which cultivation con-ditions were constantly controlled at pH 5.0 and 35 °C. In order to avoid the inhibition of cell growth at higher L-monosodium glutamate （L-MSG） concentrations, the two-stage control fermentation with substrate feeding strat-egy was applied to GABA production, with 106.87 mmol （20 g） L-MSG supplemented into the shaking-flask at 32 h and 56 h post-inoculation separately. The GABA concentration reached 526.33 mmol·L-1 at 72 h with the fer-mentation volume increased by 38%. These results will provide primary data to realize large-scale production of GABA by L. brevis CGMCC 1306.
文摘Gamma-aminobutyric acid(GABA)and glutamate are two important amino acid neurotransmitters widely present in the nervous systems of mammals,insects,round worm,and platyhelminths,while their receptors are quite diversified across different animal phyla.However,the evolutionary mechanisms between the two conserved neurotransmitters and their diversified receptors remain elusive,and antagonistic interactions between GABA and glutamate signal transduction systems,in particular,have begun to attract significant attention.In this review,we summarize the extant results on the origin and evolution of GABA and glutamate,as well as their receptors,and analyze possible evolutionary processes and phylogenetic relationships of various GABAs and glutamate receptors.We further discuss the evolutionary history of Excitatory/Neutral Amino Acid Transporter(EAAT),a transport protein,which plays an important role in the GABA-glutamate“yin and yang”balanced regulation.Finally,based on current advances,we propose several potential directions of future research.
文摘Alzheimer＇s disease （AD）, the predominant form of dementia, is a chronic, incurable neurodegenerative disorder presenting with symptoms includ- ing progressive memory loss and disturbed emotional state. It has been estimated that dementia affects over 47 million people worldwide （Prince et al., 2015）, and with 60-80% of cases attributable to AD.
基金Supported by:the Science and Technology Development Program of Sichuan Provincial Science and Technology Department, No 05SG022-013
文摘BACKGROUND： Gamma-aminobutyric acid transporter plays an important role in gamma-aminobutyric acid metabolism, and is highly associated with epilepsy seizures. Pathologically, astrocytes release active substances that alter neuronal excitability, and it has been demonstrated that astrocytes play a role in epileptic seizures. OBJECTIVE： To observe changes in gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression in the hippocampus and cortex of the temporal lobe in rats with pentylenetetrazol-induced chronic epilepsy. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment was performed at the Department of Neurobiology, Third Military University of Chinese PLA between January 2006 and December 2007. MATERIALS： Pentylenetetrazol was purchased from Sigma, USA; rabbit anti-rat gammaaminobutyric acid transporter 1 and glial fibrillary acidic protein were from Chemicon, USA. METHODS： A total of 40 Sprague Dawley rats were divided into model and control groups. Rat models of chronic epilepsy were created by pentylenetetrazol kindling, and were subdivided into 3-, 7-, and 14-day kindling subgroups. MAIN OUTCOME MEASURES： Gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression, as well as the number of positive cells in the hippocampus and cortex of temporal lobe of rats, were determined by immunohistochemistry and Western blot analyses. RESULTS： Compared with the control group, the number of gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein -positive cells in the hippocampus and cortex of rats with pentylenetetrazol-induced epilepsy significantly increased, gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression increased after 3 days of kindling, reached a peak on day 7, and remained at elevated levels at day 14 （P〈 0.05）. CONCLUSION： Astrocytic activation and gamma-aminobutyric acid transporter 1 overexpression may contribute to pentylenetetrazol-induced epilepsy.
基金supported by National Natural ScienceFoundation of China (30700579)State Key Laboratory ofAnimal Nutrition (2004DA125184F0807)
文摘[ Objective] To study the effects of gamma-aminobutyric acid （GABA） on performance of lactating sows during heat stress. [ Metbod] A total of 14 sows at the same parity and with close expected date of childbirth and similar body we：,ght were randomly divided into control group and experimental group. They were fed a common basal diet and a GABA （300 mg/kg） supplementary diet, respectively. The trial lasted for 21 d. [ Result ] The daily feed intake, lactation yield and average daily gain of piglets in the experimental group were increased by 9.4%, 28.5% and 10.7%, respectively. The backfat of lactating sows was decreased less, and the same with the weaning-oestrus interval. The survival ratio of piglets was increased by 4.5%. Compared with the control group, the content of lactose and fat increased significantly, but other components almost did not change. [Conclusien] Supplementing GABA in diet can improve the performance of lactating sows and promote the growth of piglets effectively.
基金the National Natural Science Foundation of China,No. 30560162the Natural Scientific Foundation of Guangxi Zhuang Autonomous Region,No.0542087Guangxi Health and Medical Community Scientific Research,No.200512
文摘BACKGROUND： Gamma-aminobutyric acid A （GABAA） and N-methyl-D-aspartate （NMDA） receptors are significant receptors in the central nervous system. An understanding of GABAA and NMDA receptor expression in spiral ganglion neurons （SGN） provides information for the functional role of these receptors in the auditory system. OBJECTIVE： To investigate mRNA expression of GABAA receptor （GABAAR） and NMDA receptor （NMDAR） subunits in the rat SGN. DESIGN, TIME AND SETTING： This in vitro, molecular biological study was performed at the Laboratory of Otolaryngology-Head and Neck Surgery, Guangxi Medical University, China from July 2007 to May 2008. MATERIALS： Reverse Transcriptase Kit and Taq DNA polymerase were purchased from Fermentas Burlington, ON, Canada; GABAAR and NMDAR primers were purchased from Shanghai Sangon, Shanghai, China. METHODS： SGN from 3-5 day postnatal Wistar rats was collected for primary cultures, mRNA expression of GABAAR and NMDAR subunits in the SGN was determined by reverse transcription polymerase chain reaction. MAIN OUTCOME MEASURES： Expression levels of GABAAR and NMDAR subunits were determined by quantitative analysis. RESULTS： GABAAR subunits （αl 6, β1 3, and y1 3） and NMDAR subunits （NR1, NR2A, NR2B, NR2C, NR2D, NR3A, and NR3B） were detected in the SGN. In α subunit genes of GABAAR, α1 and α3 expression was similar （P 〉 0.05） and greater than the other subunits. Of the β subunit genes, β1 subunit mRNA levels were greater than β2 and β3. Of the y subunit genes, y2 subunit mRNA levels were greater than y1 and y3. NR1 mRNA expression was the greatest of NMDAR subunits. CONCLUSION： GABAAR subunits （α1 6, β1-3, and y1-3） and NMDAR subunits （NR1, NR2A, NR2B, NR2C, NR2D, NR3A, and NR3B） were expressed in the rat SGN. Through comparison of GABAAR and NMDAR subunit expression, possible GABAAR combinations, as well as highly expressed subunit combinations, were estimated, which provided information for pharmacological and electrophysiological characteristics of GABAAR in the auditory system.
基金supported by grant from the National Key Research and Development Program of China(2018YFE0120500).
文摘The therapeutic effect of gamma-aminobutyric acid(GABA)on diabetes was spread as one of the alarming epidemics worldwide.The study aims to investigate the function of Lactobacillus brevis KLDS_(1.0727) and KLDS_(1.0373) strains as glutamic acid decarboxylase 65(GAD65)carriers capable of generating GABA by comparing in vitro free and freeze-dried models and GABA intervention in vivo.PCR amplification of gad and in vitro i.e.,(growth rate,viability at different pH,bile tolerance,and survivability in simulated gastric juice)were performed.In vivo experiments were conducted in 7 groups of C57BL/6J mice.Each group was injected with streptozotocin(Cont_(STZ),INSSTZ,LAC1_(STZ),LAC_(1MFDSTZ),LAC_(2STZ),LAC_(2MFDSTZ))daily except for the control(Cont).One group was injected with insulin(INSSTZ).The body weight and hyperglycemia in the blood were assessed weekly,post-euthanasia blood plasma parameters,insulin,and histological examination were evaluated.Results indicated L.brevis strains demonstrated a great tolerance to bile and simulated gastric juice in vitro(P<0.05).Cont_(STZ) had the highest average glucose level(6.84±6.46)mmol/L while INS_(STZ) expressed dramatically decreed in glucose level and displayed a significant decline in the average of weekly blood glucose(−5.74±3.08)mmol/L.The lowest body weight(ContSTZ)was(19.30±0.25)g.Based on the blood plasma analysis,L.brevis strains improved good cholesterol properties,liver and kidney functions,where most of these parameters fall within the average the reference range and prevent the development of symptoms of type 1 diabetes in vivo.As recommended,L.brevis should be commonly distributed as a postbiotic GABA in pharmaceutical and nutritional applications.
文摘Gamma-aminobutyric acid （GABA） and glutamate are two important amino acid neurotransmitters widely present in the nervous systems of mammals, insects, round worm, and platyhelminths, while their receptors are quite diversified across different animal phyla. However, the evolutionary mechanisms between the two conserved neurotransmitters and their diversified receptors remain elusive, and antagonistic interactions between GABA and glutamate signal transduction systems, in particular, have began to attract significant attention. In this review, we summarize the extant results on the origin and evolution of GABA and glutamate, as well as their receptors, and analyze possible evolutionary processes and phylogenetic relationships of various GABAs and glutamate receptors. We further discuss the evolutionary history of Excitatory/Neutral Amino Acid Transporter （EAAT）, a transport protein, which plays an important role in the GABA-glutamate ＂yin and yang＂ balanced regulation. Finally, based on current advances, we propose several potential directions of future research.
基金supported by the National Natural Science Foundation of China(21621004,22078239)the Beijing-Tianjin-Hebei Basic Research Cooperation Project(B2021210008)+1 种基金Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(TSBICIP-KJGG-004)the Tianjin Development Program for Innovation and Entrepreneurship(2018)。
文摘Gamma-aminobutyric acid(GABA)is a natural non-protein functio nal amino acid,which has potential for fermentation industrial production by Lactobacillus brevis.This work investigated the batch fermentation process and developed a kinetic model based on substrate restrictive model established by experimental data from L25(5~6)orthogonal experiments.In this study,the OD600 value of fermentation broth was fixed to constant after reaching its maximum because the microorganism death showed no effect on the enzyme activity of glutamate decarboxylase(GAD).As pH is one of the key parameters in fermentation process,a pH-dependent kinetic model based on radial basis function was developed to enhance the practicality of the model.Furthermore,as to decrease the deviations between the simulated curves and the experimental data,the rolling correction strategy with OD600 values that was measured in real-time was introduced into this work to modify the model.Finally,the accu racy of the rolling corrected and pH-dependent model was validated by good fitness between the simulated curves and data of the initial batch fermentation(pH 5.2).As a result,this pH-dependent kinetic model revealed that the optimal pH for biomass growth is 5.6-5.7 and for GABA production is about 5,respectively.Therefore,the developed model is practical and convenient for the instruction of GABA fermentation production,and it has instructive significance for the industrial scale.
基金the National Natural Science Foundation of China, No. 30570957the Natural Science Foundation of Hebei Province, No. C2006000152, C2007000251
文摘Glutamic acid and gamma-aminobutyric acid （GABA） influence iron content in the substantia nigra and globus pallidus, although the mechanisms of action remain unclear. The present study measured iron content and changes in divalent metal transporter 1 （DMT1） and hephaestin expression in the substantia nigra and caudate putamen, and explored the effects of GABA and glutamic acid on iron metabolism. Results demonstrated that iron content and DMT1 non iron response element [DMT1 （-IRE）] expression were significantly greater but hephaestin expression was significantly lower in the caudate putamen of the monosodium glutamate group compared with the control group. No significant difference in iron content was detected between the GABA and control groups. DMT1 （-IRE） expression was significantly reduced, but hephaestin expressiori was significantly increased in the GABA group compared with the control group. In addition, there was no significant difference in tyrosine hydroxylase expression between monosodium glutamate and GABA groups and the control group. These results suggested that glutamate affected iron metabolism in the caudate putamen by increasing DMTI（-IRE） and decreasing hephaestin expression. In addition, GABA decreased DMT1 （-IRE） expression in the caudate putamen.
文摘Objective:To investigate the effects of Toll-like receptor 4 antagonist Eritrane on neurogenesis and gamma-aminobutyric acid glutamate balance in the prefrontal lobe and hippocampus of depressive rats.Methods:100 healthy SD rats were divided into healthy control group, blank control group and Eritram group (low dose group, medium dose group and high dose group), 20 rats in each group. The depression model of rats in blank control group and Salvia miltiorrhiza group was established. After the completion of the model, rats in the blank control group were injected with normal saline and rats in the Eritrean group were injected with high, medium and low doses of Eritrean injection respectively. After 21 days of continuous administration, the total distance of spontaneous activity, the immobility time of forced swimming, the levels of gamma-aminobutyric glutamate (GABA), glutamate (Glu) and Toll-like receptor 4 (TLR-4) protein in prefrontal lobe and hippocampal neurons were measured and compared. Pearson correlation test was used to analyze the correlation between TLR4 and GABA, Glu levels in depressive rats.Results: Compared with the healthy control group, the total spontaneous activity distance of the blank control group and Eritrean group decreased significantly, and the immobility time of forced swimming increased significantly (P<0.05). There was a significant difference between the blank control group and Eritrean group (P<0.05). The rats in Eritrean group spontaneously survived with the increase of dose. The total distance increased, while the immobility time of forced swimming decreased (P<0.05). Compared with the healthy control group, the levels of GABA in the prefrontal lobe and hippocampus of rats in blank control group and Eritrean group decreased significantly, the levels of Glu and TLR4 increased significantly, and the levels of GABA in Eritrean group were higher than those in blank control group, and the levels of Glu and TLR4 were lower than those in blank control group. TLR4 and TLR4 decreased significantly (P<0.05). Pearson correlation test showed that TLR4 was negatively correlated with GABA and positively correlated with Glu (P<0.05). Conclusion: Eritrean can reduce the effects of depression on the neurogenesis of prefrontal lobe and hippocampal neurons and the balance of gamma-aminobutyric acid and glutamate in rats. The mechanism is that Eritrean can increase the level of GABA and decrease the level of Glu by antagonizing Toll-like receptor 4, thus exerting the neuroprotective effect of prefrontal lobe and hippocampal neurons.
基金This study was partially supported by the National Natural Science Foundation of China （No. 30971303）.
文摘Background Asthma is a chronic inflammatory disease characterized by reversible bronchial constriction, pulmonary inflammation and airway remodeling. Current standard therapies for asthma provide symptomatic control, but fail to target the underlying disease pathology. Furthermore, no therapeutic agent is effective in preventing airway remodeling. A substantial amount of evidence suggests that statins have anti-inflammatory properties and immunomodulatory activity. In this study, we investigated the effect of rosuvastatin on airway inflammation and its inhibitory mechanism in mucus hypersecretion in a murine model of chronic asthma. Methods BALB/c mice were sensitized and challenged by ovalbumin to induce asthma. The recruitment of inflammatory cells into bronchoalveolar lavage fluid （BALF） and the lung tissues were measured by Diff-Quik staining and hematoxylin and eosin （H＆E） staining. ELISA was used for measuring the levels of IL-4, IL-5, IL-13 and TNF-a in BALE Periodic acid-Schiff （PAS） staining was used for mucus secretion. Gamma-aminobutyric acid type A receptor （GABAAR） β2 expression was measured by means of immunohistochemistry, reverse transcription-polymerase chain reaction （RT-PCR） and Western blotting. Results Rosuvastatin reduced the number of total inflammatory cells, lymphocytes, macrophages, neutrophils, and eosinophils recruited into BALF, the levels of IL-4, IL-5, IL-13 and TNF-a in BALF, along with the histological mucus index （HMI） and GABAAR 132 expression. Changes occurred in a dose-dependent manner. Conclusions Based on its ability to reduce the inflammatory response and mucus hypersecretion by regulating GABAAR activity in a murine model of chronic asthma, rosuvastatin may be a useful therapeutic agent for treatment of asthma.
基金supported by the Korean Institute of Planning and Evaluation for Technology in Food,Agriculture,Forestry and Fishery(IPET)through the Agri-Bio Industry Technology Development Program,funded by the Ministry of Agriculture,Food and Rural Affairs(316036-3)
文摘The present study was conducted to evaluate the effects of dietary gamma-aminobutyric acid(GABA)in broiler chickens raised in high stocking density(HSD)on performance and physiological responses.A total of 900 male broiler chicks(Ross 308)at 1 d old were assigned in a 2×2 factorial arrangement to 4 treatments(10 replicates per treatment)with stocking density,7.5 birds/m^2(low stocking density;LSD)or 15 birds/m^2(HSD),and dietary GABA,0 or 100 mg/kg.Chickens raised in HSD exhibited a decrease in body weight gain in all phases(P<0.05)and feed intake in starter and whole phases(P<0.01),and an increase in feed conversion ratio in the finisher phase(P<0.01)compared with LSD-raised chickens.However,dietary GABA did not affect growth performance nor interacted with stocking density on production variables.The HSD vs.LSD increased relative liver weight on d 35 whereas dietary GABA increased relative liver weight and decreased relative bursa weight on d 21.Both stocking density and dietary GABA affected yield and quality of breast and leg muscles.Dietary GABA increased(P<0.05)width of tibia on d 35 and interacted(P=0.054)with stocking density on breaking stocking density on d 35.The HSD vs.LSD group lowered(P<0.05)feather coverage scores.Significant interaction between stocking density and GABA on surface temperature of shank on d 21 was noted(P=0.024).Dietary GABA exhibited an opposite effect on the concentrations of cecal short-chain fatty acids depending on stocking density leading to a moderate to significant interaction.Stocking density decreased alpha-1-acid glycoprotein whereas dietary GABA decreased heterophil-to-lymphocyte ratio and corticosterone in blood or serum samples.Serum biochemical parameters were altered by stocking density or dietary GABA.It is concluded that dietary GABA alleviated stress indices including corticosterone and heterophilto-lymphocyte ratio,but failed to reverse stocking density-induced growth depression.
基金JKST&IC file no.(JKST&IC/J/14/2022/342-46)(Jammu and Kashmir DST)for supporting our research.
文摘Gamma-aminobutyric acid(GABA),a ubiquitous non-protein 4-carbon amino acid present in both prokaryotic and eukaryotic organisms.It is conventionally recognized as a neurotransmitter in mammals and plays a crucial role in plants.The context of this review centers on the impact of GABA in mitigating abiotic stresses induced by climate change,such as drought,salinity,heat,and heavy metal exposure.Beyond its neurotransmitter role,GABA emerges as a key player in diverse metabolic processes,safeguarding plants against multifaceted abiotic as well as biotic challenges.This comprehensive exploration delves into the GABA biosynthetic pathway,its transport mechanisms,and its intricate interplay with various abiotic stresses.The discussion extends to the nuanced relationship between GABA and phytohormones during abiotic stress acclimation,offering insights into the strategic development of mitigation strategies against these stresses.The delineation of GABA’s crosstalk with phytohormones underscores its pivotal role in formulating crucial strategies for abiotic stress alleviation in plants.
基金supported by the Foundation of Education Department of Liaoning Province,China(No.20060211).
文摘This study aimed to investigate the protective effect of nicotine on dopaminergic neurons and its mechanisms in mice with Parkinson disease(PD)induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).C57BL/6J mice were injected with MPTP for 8 days to establish a PD model.Nicotine was given for 10 days in the nicotine therapeutic group.Animals were examined behaviorally with the pole test and traction test.Tyrosine hydroxylase(TH)andγ-aminobutyric acid(GABA)were determined by using the immunocytochem-istry(ICC)method.The ultrastructural changes of the caudate nucleus(CN)were observed under electron microscopy.The results showed that pretreatment with nicotine could improve the dyskinesia of PD mice markedly.Simultaneously,TH-positive(P<0.01)neurons and GABA-positive(P<0.05)neurons in the nicotine therapeutic group were significantly more than those in the model group.The ultrastructural injury of the nicotine therapeutic group was also ameliorated.Nicotine has protective effects on theγ-aminobutyric acid neurons and dopaminergic neurons in the MPTP-treated mice.
文摘Debates regarding the specific effects of general anesthesia on developing brains have persisted for over 30 years.A consensus has been reached that prolonged,repeated,high-dose exposure to anesthetics is associated with a higher incidence of deficits in behavior and executive function,while single exposure has a relatively minor effect on long-term neurological function.In this review,we summarize the dose-dependent neuroprotective or neurotoxic effects of gamma-aminobutyric acid type A receptor agonists,a representative group of sedatives,on developing brains or central nervous system diseases.Most preclinical research indicates that anesthetics have neurotoxic effects on the developing brain through various signal pathways.However,recent studies on low-dose anesthetics suggest that they may promote neurodevelopment during this critical period.These findings are incomprehensible for the general“dose-effect”principles of pharmacological research,which has attracted researchers'interest and led to the following questions:What is the threshold for the dual effects exerted by anesthetics such as propofol and sevoflurane on the developing brain?To what extent can their protective effects be maximized?What are the underlying mechanisms involved in these effects?Consequently,this issue has essentially become a“mathematical problem.”After summarizing the dose-dependent effects of gamma-aminobutyric acid type A receptor agonist sedatives in both the developing brain and the brains of patients with central nervous system diseases,we believe that all such anesthetics exhibit specific threshold effects unique to each drug.These effects range from neuroprotection to neurotoxicity,depending on different brain functional states.However,the exact values of the specific thresholds for different drugs in various brain states,as well as the underlying mechanisms explaining why these thresholds exist,remain unclear.Further in-depth exploration of these issues could significantly enhance the therapeutic translational value of these anesthetics.
