Cognitive dysfunction in schizophrenia patients caused by downregulation of γ-aminobutyric acid receptor subunits

BACKGROUND The expression pattern of gamma aminobutyric acid(GABA)receptor subunits are commonly altered in patients with schizophrenia,which may lead to nerve excitation/inhibition problems,affecting cognition,emotion,and behavior.AIM To explore GABA receptor expression and its relationship with schizophrenia and to provide insights into more effective treatments.METHODS This case-control study enrolled 126 patients with schizophrenia treated at our hospital and 126 healthy volunteers who underwent physical examinations at our hospital during the same period.The expression levels of the GABA receptor subunits were detected using 1H-magnetic resonance spectroscopy.The recognized cognitive battery tool,the MATRICS Consensus Cognitive Battery,was used to evaluate the scores for various dimensions of cognitive function.The correlation between GABA receptor subunit downregulation and schizophrenia was also analyzed.RESULTS Significant differences in GABA receptor subunit levels were found between the case and control groups(P<0.05).A significant difference was also found between the case and control groups in terms of cognitive function measures,including attention/alertness and learning ability(P<0.05).Specifically,as the expression levels of GABRA1(α1 subunit gene),GABRB2(β2 subunit gene),GABRD(δsubunit),and GABRE(εsubunit)decreased,the severity of the patients’condition increased gradually,indicating a positive correlation between the downregulation of these 4 receptor subunits and schizophrenia(P<0.05).However,the expression levels of GABRA5(α5 subunit gene)and GABRA6(α6 subunit gene)showed no significant correlation with schizophrenia(P>0.05).CONCLUSION Downregulation of the GABA receptor subunits is positively correlated with schizophrenia.In other words,when GABA receptor subunits are downregulated in patients,cognitive impairment becomes more severe.

γ-aminobutyric acid B2 receptor:A potential therapeutic target for cholangiocarcinoma in patients with diabetes mellitus

BACKGROUND The association between diabetes mellitus(DM)and the increased risk and progression of cholangiocarcinoma(CCA)has been reported with unclear underlying mechanisms.Previous studies showed thatγ-aminobutyric acid(GABA)B2 receptor(GABBR2)was upregulated in CCA cells cultured in high glucose(HG)conditions.Roles of GABA receptors in CCA progression have also been studied,but their association with DM and hyperglycemia in CCA remains unclarified.AIM To investigate the effects of hyperglycemia on GABBR2 expression and the potential use of GABBR2 as a CCA therapeutic target.METHODS CCA cells,KKU-055 and KKU-213A,were cultured in Dulbecco Modified Eagle’s Medium supplemented with 5.6 mmol/L(normal glucose,NG)or 25 mmol/L(HG)glucose and assigned as NG and HG cells,respectively.GABBR2 expression in NG and HG cells was investigated using real-time quantitative polymerase chain reaction and western blot.Expression and localization of GABBR2 in CCA cells were determined using immunocytofluorescence.GABBR2 expression in tumor tissues from CCA patients with and without DM was studied using immunohistochemistry,and the correlations of GABBR2 with the clinicopathological characteristics of patients were analyzed using univariate analysis.Effects of baclofen,a GABA-B receptor agonist,on CCA cell proliferation and clonogenicity were tested using the MTT and clonogenic assays.Phospho-kinases arrays were used to screen the affected signaling pathways after baclofen treatment,and the candidate signaling molecules were validated using the public transcriptomic data and western blot.RESULTS GABBR2 expression in CCA cells was induced by HG in a dose-and time-dependent manner.CCA tissues from patients with DM and hyperglycemia also showed a significantly higher GABBR2 expression compared with tumor tissues from those with euglycemia(P<0.01).High GABBR2 expression was significantly associated with a poorer non-papillary histological subtype but with smaller sizes of CCA tumors(P<0.05).HG cells of both tested CCA cell lines were more sensitive to baclofen treatment.Baclofen significantly suppressed the proliferation and clonogenicity of CCA cells in both NG and HG conditions(P<0.05).Phospho-kinase arrays suggested glycogen synthase kinase 3(GSK3),β-catenin,and the signal transducer and activator of transcription 3(STAT3)as candidate signaling molecules under the regulation of GABBR2,which were verified in NG and HG cells of the individual CCA cell lines.Cyclin D1 and c-Myc,the common downstream targets of GSK3/β-catenin and STAT3 involving cell proliferation,were accordingly downregulated after baclofen treatment.CONCLUSION GABBR2 is upregulated by HG and holds a promising role as a therapeutic target for CCA regardless of the glucose condition.

Relationship of nocturnal concentrations of melatonin, gamma-aminobutyric acid and total antioxidants in peripheral blood with insomnia after stroke： study protocol for a prospective non-randomized controlled trial

Melatonin and gamma-aminobutyric acid（GABA） have been shown to regulate sleep. The nocturnal concentrations of melatonin, GABA and total antioxidants may relate to insomnia in stroke patients. In this prospective single-center non-randomized controlled clinical trial performed in the China Rehabilitation Research Center, we analyzed the relationship of nocturnal concentrations of melatonin, GABA and total antioxidants with insomnia after stroke. Patients during rehabilitation of stroke were recruited and assigned to the insomnia group or non-insomnia group. Simultaneously, persons without stroke or insomnia served as normal controls. Each group contained 25 cases. The primary outcome was nocturnal concentrations of melatonin, GABA and total antioxidants in peripheral blood. The secondary outcomes were Pittsburgh Sleep Quality Index, Insomnia Severity Index, Epworth Sleepiness Scale, Fatigue Severity Scale, Morningness-Eveningness Questionnaire（Chinese version）, and National Institute of Health Stroke Scale. The relationship of nocturnal concentrations of melatonin, GABA and total antioxidants with insomnia after stroke was analyzed and showed that they were lower in the insomnia group than in the non-insomnia group. The severity of stroke was higher in the insomnia group than in the non-insomnia group. Correlation analysis demonstrated that the nocturnal concentrations of melatonin and GABA were associated with insomnia after stroke. This trial was registered at Clinical Trials.gov, identifier： NCT03202121.

Immunohisto chemical Study on the Effects of Pyrethroids on Gluta-mate and γ-Aminobutyric Acid in Rat Central Nervous System

Objective\ In order to study the effects of pyrethroids on glutamate (Glu) and gamma aminobutyric acid (GABA) in rat central nervous system. Methods\ Male SD rats were treated with permethrin (7 mg/kg, i.p) or cypermethrin (70 mg/kg, i.p) once a day for 3 days. Glu and GABA immunoreactive cells and transmitters in CNS were studied by immunohistochemical method. Results\ The total number, percentage of positive area and integral optical density of glutamate immunoreactive cell in cerebral cortex, hippocampus decreased significantly in permethrin or cypermethrin, while GABA was enhanced. Cypermethrin is more tent than permethrin on either Glu or GABA. Conclusion\ Disturbance of Glu and GABA is likely to play a role in the development of pyrethroids excitatory neurotoxicity.

Effects of Rhizoma Acori Tatarinowii extracts on gamma-aminobutyric acid type A receptor alpha 1 subunit brain expression during development in a recurrent seizure rat model

Extracts from Rhizoma Acori Tatarinowii （Grassleaf Sweetflag Rhizome, Shichangpu） have been shown to improve learning and memory, reduce anxiety, allay excitement, and suppress seizures. Rhizoma Acori Tatarinowii extracts interact with y-aminobutyric acid and activate the y-aminobutyric acid type A receptor, although few studies have addressed the precise effects of v-aminobutyric acid type A receptor al subunit. In the present study, y-aminobutyric acid type A receptor al subunit protein expression in the cerebral cortex and hippocampus, and pathological scores of brain injury, were significantly greater following recurrent seizures, but significantly decreased following treatment with Rhizoma Acori Tatarinowii extracts. These results indicated that Rhizoma Acori Tatarinowii extracts down-regulated y-aminobutyric acid type A receptor al subunit protein expression in the cerebral cortex and hippocampus and protected seizure-induced brain injury during development.

Hippocampal and cortical expression of gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein in pentylenetetrazol-induced chronic epileptic rats

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.

Gamma-aminobutyric acid promotes human hepatocellular carcinoma growth through overexpressed gamma-aminobutyric acid A receptor α3 subunit

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.

On-line near-infrared spectroscopy optimizing and monitoring biotransformation process of γ-aminobutyric acid

Near-infrared spectroscopy （NIRS） with its fast and nondestructive advantages can be qualified for the real-time quantitative analysis. This paper demonstrates that NIRS combined with partial least squares （PLS） regression can be used as a rapid analytical method to simultaneously quantify L-glutamic acid （L- GIu） and γ-aminobutyric acid （GABA） in a biotransformation process and to guide the optimization of production conditions when the merits of NIRS are combined with response surface methodology. The high performance liquid chromatography （HPLC） reference analysis was performed by the o-phthaldialdehyde pre-column derivatization. NIRS measurements of two batches of 141 samples were firstly analyzed by PLS with several spectral pre-processing methods. Compared with those of the HPLC reference analysis, the resulting determination coefficients （R2）, root mean square error of prediction （RMSEP） and residual predictive deviation （RPD） of the external validation for the L-GIu concentration were 99.5%, 1.62 g/L, and 11.3, respectively. For the GABA concentration, R2, RMSEP, and RPD were 99.8%, 4.00 g/L, and 16.4, respectively. This NIRS model was then used to optimize the biotransformation process through a Box- Behnken experimental design. Under the optimal conditions without pH adjustment, 200 gjL L-GIu could be catalyzed by 7148 U/L glutamate decarboxylase （GAD） to GABA, reaching 99% conversion at the fifth hour. NIRS analysis provided timely information on the conversion from L-GIu to GABA. The results suggest that the NIRS model can not only be used for the routine profiling of enzymatic conversion, providing a simple and effective method of monitoring the biotransformation process of GABA, but also be considered to be an optimal tool to guide the optimization of production conditions.

Effects of Gamma-Aminobutyric Acid on Performance of Lactating Sows during Heat Weather

[ 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.

Effect of Propofol on Glutamate and γ-aminobutyric Acid Release from Rat Hippocampal Synaptosomes

To investigate the effect of propofol on the release of glutamate and γ-aminobutyric acid （GABA） from rat hippocampal synatosomes, synaptosomes was made from hippocampus and incubated with artificial cerebrospinal fluid （aCSF）. With the experiment of Ca^2＋-dependent release of glutamate and GABA, dihydrokainic acid （DHK） and nipectic acid were added into aCSF. For the observation of Ca^2＋-independent release of glutamate and GABA, no DHK, nipectic acid and Ca^2＋ were added from aCSF. The release of glutamate and GABA were evoked by 20 μmol/L veratridine or 30 mmol/L KCh The concentration of glutamate and GABA in aCSF was measured by using high-performance liquid chromatography （HPLC）. 30, 100 arid 300 μmol/L propofol significantly inhibited veratridine-evoked Ca^2＋-dependent release of glutamate and GABA （P〈0. 01 or P〈0. 05）, However, propofol showed no effect on elevated KCl-evoked Ca^2＋-dependent release of glutamate and GABA （P〉0, 05）, Veratridine or elevated KCI evoked Ca^2＋-independent release of glutamate and GABA was not affected significantly by propofol （P〉0.05）. Propofol could inhibit Ca^2＋- dependent release of glutamate and GABA, However, it has no effect on the Ca^2＋-independent release of glutamate and GABA,

Overexpression of γ-aminobutyric acid transporter subtype I leads to susceptibility to Kainic acid-induced seizure in transgenic mice

γ-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter, and the GABAergic synaptic transmission is normally terminated by the rapid uptake through GABA transporters. With transgenic mice ubiquitously overexpressing GABA transporter subtype I (GAT1), the present study explored the pathophysiological role of GAT1 in epileptogenesis. Though displaying no spontaneous seizure activity, these mice exhibit altered electroencephalographic patterns and increased susceptibility to seizure induced by kainic acid. In addition, the GABAA receptor and glutamate transporters are up-regulated in transgenic mice, which perhaps reflects a compensatory or corrective change to the elevated level of GAT1. These preliminary findings support the hypothesis that excitatory and inhibitory neurotransmission, and seizure susceptibility can be altered by neurotransmitter transporters.

γ-Aminobutyric acid transporter (GAT1) overexpression in mouse affects the testicular morphology

γ-Aminobutyric acid and GABAergic receptors were previously reported to be distributed in reproductive systems besides CNS and predicted to participate in the modulation of testicular function. γ-Aminobutyric acid transporter was implicated to be involved in this process. However, the potential role of γ-aminobutyric transporter in testis has not been explored. In this study, we investigated the existence of mouse γ-aminobutyric acid transporter subtype I (mGAT1) in testis. Wild-type and transgenic mice, which overexpressing mGAT1 in a variety of tissues, especially in testis, were primarily studied to approach the profile of mGAT1 in testis. Mice with overexpressed mGAT1 develop normally but with reduced mass and size of testis as compared with wild-type. Testicular morphology of transgenic mice exhibited overt abnormalities including focal damage of the spermatogenic epithelium accompanied by capillaries proliferation and increased diameter of seminiferous tubules lumen. Reduced number of spermatids was also found in some seminiferous tubules. Our results clearly demonstrate the presence of GAT1 in mouse testis and imply that GAT1 is possibly involved in testicular function.

Expression of gamma-aminobutyric acid A receptor subunits aα_1,β_1,γ_2 mRNA in rats with hepatic encephalopathy

AIM To investigate the mRNA expression of gammaaminobutyric acid A (GABAA) receptor subunits α1,β1, γ2in different parts of the brain of rats with hepaticencephalopathy.METHODS: Twelve adult male Sprague-Dawley rats were randomly divided into two groups: (1) hepatic encephalopathy model group (n = 6), which was induced by intraperitoneal injection of thioacetamide (TAA, 350 mg/kg) for threeconsecutive days; (2) control group (n = 6), in which the rats were treated with same dose of normal saline solution. After the freeze slice of cerebrum was made,in situ hybridization was used to detect the mRNA of GABAA receptor subunits α1, β1, and γ2 in rat cerebral cortex, basal nuclei, substantia nigra and hippocampi. Image data were collected and analyzed quantitatively by QWin550CWmodel image signal gather and analysis system. RESULTS: In rats with hepatic encephalopathy, mRNA expression levels of GABAA receptor subunits α1, β1 increased significantly in basal nuclei, substantia nigra pars compacta, substantia nigra pars reticularis and hippocampi (144.7±15.67/184.14±4.41, 60.61±33.66/113.07±32.44,87.71± 21.25/128.40±18.85, 122.34±5.56/161.60±4.56,123.29±5.21/140.65±4.15, 123.40±4.42/140.09±4.52,124.76±4.18/140.09±4.12, 141.62±15.09/182.80 ±5.20,69.13±30.74/134.21±43.76, 87.87±25.16/151.01±19.49,122.14±6.30/162.33±3.92, 122.81±5.09/137.19±7.12,123.00±4.63/138.11±5.92, 125.75 ±2.43/138.81±6.10,P＜0.01), but did not change in the cerebral cortex compared to the control group. Similar changes were found in the mRNA expression levels of GABAA receptor subunit γ2,which increased significantly in basal nuclei, substantia nigra pars compacta, substantia nigra pars reticularis (136.81±26.41/167.97±16.23, 51.00±36.14/113.18±36.52, 86.35±20.30/126.90±19.74, P＜0.01), CA1 of hippocampal (162.15±9.05/178.62±6.45, P＜0.05), and no changes were found in the cerebral cortex and CA2, CA3, CA4 of hippocampi.CONCLUSION: In rats with hepatic encephalopathy, mRNA expression levels of GABAA receptor subunits α1,β1, γ2 increase significantly in basal nuclei, substantia nigra and hippocampi, suggesting that the changes of mRNA expression levels in GABAA receptor subunits may contribute to the pathogenesis of hepatic encephalopathy.

Expression of gamma-aminobutyric acid type A receptor α_2 subunit in the dorsal root ganglion of rats with sciatic nerve injury

The γ-aminobutyric acid neurotransmitter in the spinal cord dorsal horn plays an important role in pain modulation through primary afferent-mediated presynaptic inhibition. The weakening of γ-aminobutyric acid-mediated presynaptic inhibition may be an important cause of neuropathic pain. γ-aminobutyric acid-mediated presynaptic inhibition is related to the current strength of γ-aminobutyric acid A receptor activation. In view of this, the whole-cell patch-clamp technique was used here to record the change in muscimol activated current of dorsal root ganglion neurons in a chronic constriction injury model. Results found that damage in rat dorsal root ganglion neurons following application of muscimol caused concentration-dependent activation of current, and compared with the sham group, its current strength and γ-aminobutyric acid A receptor protein expression decreased. Immunofluorescence revealed that γ-aminobutyric acid type A receptor α2 subunit protein expression decreased and was most obvious at 12 and 15 days after modeling. Our experimental findings confirmed that the y-aminobutyric acid type A receptor α2 subunit in the chronic constriction injury model rat dorsal root ganglion was downregulated, which may be one of the reasons for the reduction of injury in dorsal root ganglion neurons following muscimol-activated currents.

Gamma-aminobutyric acid A receptor and N-methyl-D-aspartate receptor subunit expression in rat spiral ganglion neurons

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.

Effect of propofol on the reactivity of acetylcholinesterase,N-methyl-D-aspartate receptors,and gamma-aminobutyric acid receptors in the hippocampus of aged rats after chronic cerebral ischemia

We induced ischemic brain injury in aging rats to examine the effects of varying doses of propofol on hippocampal activities of acetylcholinesterase, N-methyI-D-aspartate receptors, and y-aminobutyric acid receptors. Propofol exhibited no obvious impact on acetylcholinesterase activity, but directly activated the y-aminobutyric acid receptor. The neuroprotective function of propofol on the hippocampus of aging rats following cerebral ischemic injury may be related to altered activities of y-aminobutyric acid receptors and N-methyI-D-aspartate receptors.

Motor inhibition efficiency in healthy aging: the role of γ-aminobutyric acid

The ability to cancel a motor response is critical for optimal functioning in various facets of daily life. Hence, efficient inhibitory motor control is a key function throughout the lifespan. Considering the fact that inhibitory motor function gradually declines with advancing age, it is not surprising that the study of motor inhibition in this age group is gaining considerable interest. In general, we can distinguish between two prominent types of motor inhibition, namely proactive and reactive inhibition. Whereas the anticipation for upcoming stops(proactive inhibition) appears readily preserved at older age, the ability to stop an already planned or initiated action(reactive inhibition) generally declines with advancing age. The differential impact of aging on proactive and reactive inhibition at the behavioral level prompts questions about the neural architecture underlying both types of inhibitory motor control. Here we will not only highlight the underlying structural brain properties of proactive and reactive inhibitory control but we will also discuss recent developments in brain-behavioral approaches, namely the registration of neurochemical compounds using magnetic resonance spectroscopy. This technique allows for the direct detection of the primary inhibitory neurotransmitter in the brain, i.e., γ-aminobutyric acid, across the broader cortical/subcortical territory, thereby opening new perspectives for better understanding the neural mechanisms mediating efficient inhibitory control in the context of healthy aging. Ultimately, these insights may contribute to the development of interventions specifically designed to counteract age-related declines in motor inhibition.

A Two-stage pH and Temperature Control with Substrate Feeding Strategy for Production of Gamma-aminobutyric Acid by Lactobacillus brevis CGMCC 1306

由乳杆菌 brevis CGMCC 1306 优化 gamma-aminobutyric 酸(伽马氨基丁酸) 的生产的方法被调查。结果显示房间生长在 pH 是最大的 5.0，当时 4.5 是的 pH 对伽马氨基丁酸更好形成。为细胞生长的最佳的温度(35 ????

A comparison study on structure-function relationship of polysaccharides obtained from sea buckthorn berries using different methods:antioxidant and bile acid-binding capacity

In this study,the structural characters,antioxidant activities and bile acid-binding ability of sea buckthorn polysaccharides(HRPs)obtained by the commonly used hot water(HRP-W),pressurized hot water(HRP-H),ultrasonic(HRP-U),acid(HRP-C)and alkali(HRP-A)assisted extraction methods were investigated.The results demonstrated that extraction methods had significant effects on extraction yield,monosaccharide composition,molecular weight,particle size,triple-helical structure,and surface morphology of HRPs except for the major linkage bands.Thermogravimetric analysis showed that HRP-U with filamentous reticular microstructure exhibited better thermal stability.The HRP-A with the lowest molecular weight and highest arabinose content possessed the best antioxidant activities.Moreover,the rheological analysis indicated that HRPs with higher galacturonic acid content and molecular weight showed higher viscosity and stronger crosslinking network(HRP-C,HRP-W and HRP-U),which exhibited stronger bile acid binding capacity.The present findings provide scientific evidence in the preparation technology of sea buckthorn polysaccharides with good antioxidant and bile acid binding capacity which are related to the structure affected by the extraction methods.

Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.