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Role of astrocytic glutamate transporter in alcohol use disorder

World Journal of Psychiatry 2016年第1期6卷 31-42页

作者： Jennifer R Ayers-Ringler Yun-Fang Jia Yan-Yan Qiu Doo-Sup Choi Neurobiology of Disease PhD Program Mayo Graduate SchoolMayo Clinic Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic College of Medicine

Alcohol use disorder(AUD) is one of the most widespread neuropsychiatric conditions, having a significant health and socioeconomic impact. According to the 2014 World Health Organization global status report on alcohol and health, the harmful use of alcohol is responsible for 5.9% of all deaths worldwide. Additionally, 5.1% of the global burden of disease and injury is ascribed to alcohol(measured in disability adjusted life years, or disability adjusted life years). Although the neurobiological basis of AUD is highly complex, the corticostriatal circuit contributes significantly to the development of addictive behaviors. In-depth investigation into the changes of the neurotransmitters in this circuit, dopamine, gamma-aminobutyricacid, and glutamate, and their corresponding neuronal receptors in AUD and other addictions enable us to understand the molecular basis of AUD. However, these discoveries have also revealed a dearth of knowledge regarding contributions from nonneuronal sources. Astrocytes, though intimately involved in synaptic function, had until recently been noticeably overlooked in their potential role in AUD. One major function of the astrocyte is protecting neurons from excitotoxicity by removing glutamate from the synapse via excitatory amino acid transporter type 2. The importance of this key transporter in addiction, as well as ethanol withdrawal, has recently become evident, though its regulation is still under investigation. Historically, pharmacotherapy for AUD has been focused on altering the activity of neuronal glutamate receptors. However, recent clinical evidence has supported the animal-based findings, showing that regulating glutamate homeostasis contributes to successful management of recovery from AUD.

关键词： Alcohol Addiction glutamate Astrocyte Excitatory amino acid transporter type 2 Glia Striatum

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Efect of the Gad system on Actinobacillus succinogenes during acid stress

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Systems Microbiology and Biomanufacturing 2022年第1期2卷 177-185页

作者： Chunmei Chen Qun Zhang Junzhu Qian Dan Wu Pengcheng Chen Pu Zheng The Key Laboratory of Industrial Biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi 214122China

The glutamate decarboxylase(Gad)system is an important amino acid-dependent acid resistance system commonly found in microorganisms.Actinobacillus succinogenes is one of the best natural producers of succinic acid(SA)but lacks glutamate decarboxylase.This study assessed the efects of Gad system introduction into A.succinogenes.The recombinant strains gadB-SW and gadBC-SW were constructed by heterologous expression of gadB alone,or gadB together with gadC,respectively.After 1.0 and 1.5 h of acid stress at pH 4.6,cell survival of gadBC-SW was greater than gadB-SW.The growth of gadB-SW and gadBC-SW was both afected by the expression of heterologous proteins and byγ-aminobutyric acid,with gadBC-SW growth reduced at a neutral pH.SA production in acidic conditions was evaluated by a shake fask and by 3-L bioreactor fermentation.The results showed gadBC-SW to increase SA production by 8.4%in shake fask compared to the parent strain,SW.For a 3-L bioreactor batch fermentation under acidic environment,the highest conversion rate of sugar to SA was observed for gadBC-SW,reaching 96%.However,SA concentration by gadBC-SW was only 47 g/L and 31 g/L at pH 6.5 and pH 6.0,respectively.In summary,the introduction of heterologous gadB and gadC into A.succinogenes not only improved acid tolerance but also infuenced the synthesis of SA and added a metabolic burden.

关键词： Actinobacillus succinogenes Acid stress glutamate decarboxylase Succinic acid glutamate

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Mammary cell proliferation and catabolism of adipose tissues in nutrition-restricted lactating sows were associated with extracellular high glutamate levels

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Journal of Animal Science and Biotechnology 2019年第1期10卷 172-182页

作者： Heju Zhong Peng Wang Yumo Song Xiaoling Zhang Lianqiang Che Bin Feng Yan Lin Shengyu Xu Jian Li De Wu Qiaofeng Wu Zhengfeng Fang Key Laboratory for Animal Disease Resistance Nutrition of the Ministry of Education Animal Nutrition InstituteSichuan Agricultural University Acupuncture and Moxibustion College Chengdu University of Traditional Chinese Medicine

Background: Persistent lactation,as the result of mammary cellular anabolism and secreting function,is dependent on substantial mobilization or catabolism of body reserves under nutritional deficiency.However,little is known about the biochemical mechanisms for nutrition-restricted lactating animals to simultaneously maintain the anabolism of mammary cells while catabolism of body reserves.In present study,lactating sows with restricted feed allowance(RFA)(n = 6),24% feed restriction compared with the control(CON) group(n = 6),were used as the nutrition-restricted model.Microdialysis and mammary venous cannulas methods were used to monitor postprandial dynamic changes of metabolites in adipose and mammary tissues.Results: At lactation d 28,the RFA group showed higher(P glutamate and insulin levels,increased(P glutamate concentration.As for mammary glands,compared with the CON group,the RFA group had up-regulated(P glutamate concentration,while expression of cell proliferation related genes and concentrations of most metabolites in mammary veins were not different(P > 0.05) between groups.Accordingly,piglet performance and milk yield did not differ(P > 0.05) between groups.It would appear that activation of Notch signaling and adequate supply of glutamate might assist mammogenesis.Conclusions: Mammary cell proliferation and catabolism of adipose tissues in nutrition-restricted lactating sows were assoc

关键词： glutamate Insulin sensitivity Lipolysis Mammary cell proliferation

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glutamate and Caffeine intake of Some Snacks and Drinks in Saudi Arabia

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Food and Nutrition Sciences 2011年第2期2卷 162-167页

作者： Magda I. Hassan Najat A. Al-Abbad 不详

The aim of this study was to estimate the intake level of glutamate and caffeine from some snacks and drinks. The survey was carried out during 2008 to 2009 in 3 selected governorates (Al-Hassa, Al- Katif and AD-Dammam) localized in the eastern area of Saudi Arabia. The age of study participants (298) was ranged between less than 4 – over 30 years. The snacks and drinks consumption data were gathered and calculated using the frequency methods. Forty nine samples of snacks and beverages were analyzed by High Performance Liquid Chromatography (HPLC) for glutamate and caffeine contents. The results indicated that total intake of snacks, chocolates and drinks were significantly correlated (spearman r = 0.856, 0.591, 0.943, p = 0.0) with total intake of glutamate and caffeine. The mean of caffeine intake was 40.4± 44.5 mg, while the mean of glutamate intake was 0.134± 0.146 mg. The highest concentration of glutamate was in Pringles with Ketchup (0.420), Bugles Smoking BBQ (0.660) and Indomie with Vegetables (0.860). The high caffeine concentrations of Kit Kat, Ulker and Galaxy samples were 166, 165.5, and 134.5 mg/kg respectively, while the beverages, the high caffeine concentrations were presented in energy drinks like Red bull (345.5), Power Horse (339.0) and Bugzy(333.0) mg/L. The children aged between 4– 8 were the most consumers of snacks which containing glutamate, while the adolescents consumed more chocolates and beverages which containing caffeine. These finding suggests that consumption of salty snacks, and sugar-sweetened beverages is mounting between important categories in the community, so interventions focusing on increasing physical activity and fruit and vegetable consumption will have an impact on obesity control and promoting health.

关键词： glutamate Caffeine Snacks Eating Habits Drinks KSA HPLC

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glutamate－IMMUNOREACTIVE　NEURONS　IN　MEDULLARY　RAPHE－CEREBELLUM　PATHWAY　IN　THE　KITTEN

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Journal of Pharmaceutical Analysis 1996年第1期10卷 1-5,30页

作者：江赛男刘荣桓

Using a combined microsphere retrograde transport with immunofluorescence technique,the glutamate-immunoreactive neurons in the medullary raphe nuclei that project to the cerebellar cortex were investigated in the present study.The cells double-labeled by glutamate-immunoresctivity and microspheres were found in all medullary raphe nuclei.Among all the cerebellar projection neurons in the medullary raphe nuclei,(49. 49±2.78)% (±)in pallidus (NRP),(62.02±3. 62) % in obscures (NRD),(3. 03±3. 03) % in magnus (NRM) were immunoreactive to glutamate.The results raise the possibility that the cerehellar vermal cortex (lobules Ⅴ-Ⅶ) may receive some excitatory input from medullary raphe nuclei to affect the function of the cerebellum.

关键词： glutamate raphe nuclei projection cerebellum

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glutamate as a Neural Stress Factor in Humans and Animals

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Journal of Behavioral and Brain Science 2019年第2期9卷 13-25页

作者： Bogdan Feliks Kania Katarzyna Ferdyn Tomasz Wojnar Grzegorz Lonc Veterinary Institute University Center for Veterinary Medicine Jagiellonian University Agricultural University in Cracow Cracow Poland Department of Anatomy and Pathomorphology University Center for Veterinary Medicine Jagiellonian University Agricultural University in Cracow Cracow Poland

L-glutamic acid (glutamate-Glu) serves as one form with very strong stimulatory neurotransmitter (near aspartic, kainic, alpha-amino-3-hydroxy-5-me- thyl-4-izoxazole propionic acid (AMPA), chinolic and L-homocysteinic acid, glycine and D-serine) at the majority of neural excitatory synapse in the mammals and nonmammals central, sympathetic nervous system (CNS and SNS, respectively) and in different peripheral tissues and organ. It mediates interactions via stimulation a variety ionotropic N-methyl-D-As- partate (NMDA), AMPA and kainate receptors (ligand gated calcium channels) and III groups of the metabotropic glutamate receptors (mGluR1-8) family members (G-protein coupled receptors). It is good known different neuromodula-tion/interaction between Glu and norepinephrine (NE), dopamine (DA), gamma-amino-butyric acid (GABA), oxytocin/vasopressin (Oxy/AVP) and steroid receptors during stress in the central nervous system. In this review we describe the molecular structure of these glutamatergic receptors and discuss they neuropharmacology and clinical use probability of their antagonist, in stress particularly. On the other hand it was interesting if Glu can increase catecholamine (CA) release from motivational structures as stressoric factor in hypothalamo-pituitary adrenal axis (HPA) in the stress inducing processes. Our findings show that Glu more influences the brain’s motivational structure, which may indicate its contribution to the stress response by direct modulating the amount of catecholamine released.

关键词： glutamate Catecholamine HPA Axis Stressor Neurotoxicity Disorders

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glutamate-induced swelling of cultured astrocytes is mediated by metabotropic glutamate receptor

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Science China(Life Sciences) 1996年第5期39卷 517-522页

作者：袁芳王天佑 Beijing Neurosurgical Institute Beijing 100050 China

The effects of glutamate and its agonists and antagonists on the swelling of cultured astrocytes were studied. Swelling of astrocytes was measured by [3H]-O-methyl-D-glucose uptake. glutamate at 0.5, 1 and 10mmol/L and irons-l-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD), a metabotropic glutamate receptor (mGluR) agonist, at 1 mmol/L caused a significant increase in astrocytic volume, whereas alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) was not effective. L-2-amino-3-phosphonopropionic acid (L-AP3), an antagonist of mGluR, blocked the astrocytic swelling induced by trans-ACPD or glutamate. In Ca2+-free condition, glutamate was no longer effective. Swelling of astrocytes induced by glutamate was not blocked by CdCl2 at 20 μmol/L, but significantly reduced by CdCl2 at 300 μmol/L and dantrolene at 30 μmol/L. These findings indicate that mGluR activation results in astrocytic swelling and both extracellular calcium and internal calcium stores play important roles in the

关键词： glutamate trans-ACPD astrocyte swell dantrolene Ca2+

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Abundance and significance of neuroligin-1 and glutamate in Hirschsprung's disease

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World Journal of Gastroenterology 2015年第23期21卷 7172-7180页

作者： Jian Wang Hao Du Ya-Ru Mou Jian-Yi Niu Wen-Tong Zhang Hong-Chao Yang Ai-Wu Li Department of Pediatric Surgery Qilu Hospital Shandong University Shandong University School of Medicine Department of Cardiology Provincial Hospital Affiliated to Shandong University Department of Neurology Qingzhou Clinical School Weifang Medical College

AIM: To investigate the abundance and potential diagnostic significance of neuroligin-1 and glutamate(Glu) in Hirschsprung's disease(HSCR).METHODS: Ninety children with HSCR and 50 children without HSCR matched for similar nutritional status, age and basal metabolic index were studied. The expression and localization of neuroligin-1 and Glu were assessed using double-labeling immunofluorescence staining of longitudinal muscles with adherent myenteric plexus from the surgically excised colon of children with HSCR. Western blot analysis, quantitative real-time PCR(q RT-PCR) and immunohistochemistry were performed to evaluate the abundance of neuroligin-1 and Glu in different HSCR-affected segments(ganglionic, transitional, and aganglionic segments). Enzyme-linked immunosorbent assay(ELISA) was used to detect and compare serum Glu levels in the long-segment HSCR, short-segment HSCR and non-HSCR samples.RESULTS: Neuroligin-1 and Glu were co-expressed highest to lowest in the ganglionic, transi tional and aganglionic segments based on Western blot(neuroligin-1: 0.177 ± 0.008 vs 0.101 ± 0.006, 0.177 ± 0.008 vs 0.035 ± 0.005, and 0.101 ± 0.006 vs 0.035 ±0.005, P < 0.005; Glu: 0.198 ± 0.006 vs 0.115 ± 0.008, 0.198 ± 0.006 vs 0.040 ± 0.003, and 0.115 ± 0.008 vs 0.040 ± 0.003, P < 0.005) and q RT-PCR(neuroligin-1: 9.58 × 10-5 ± 9.94 × 10-6 vs 2.49 × 10-5 ± 1.38 × 10-6, 9.58 × 10-5 ± 9.94 × 10-6 vs 7.17 × 10-6 ± 1.12 × 10-6, and 2.49 × 10-5 ± 1.38 × 10-6 vs 7.17 × 10-6 ± 1.12 × 10-6, P < 0.005). Serum Glu level was the highest to lowest in the non-HSCR, short-type HSCR and long-type HSCR samples based on ELISA(in nmol/μL, 0.93 ± 0.31 vs 0.57 ± 0.25, 0.93 ± 0.31 vs 0.23 ± 0.16, and 0.57 ± 0.25 vs 0.23 ± 0.16, P < 0.005).CONCLUSION: Neuroligin-1 and Glu may represent new markers of ganglion cells, whose expression may correlate with the pathogenesis, diagnosis, differential diagnosis or classification of HSCR.

关键词： Neuroligin-1 Hirschsprung's disease glutamate Ganglion cells Pathogenesis

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Regulation of hepatic EAAT-2 glutamate transporter expression in human liver cholestasis

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World Journal of Gastroenterology 2014年第6期20卷 1554-1564页

作者： Mustapha Najimi Xavier Stéphenne Christine Sempoux Etienne Sokal Université Catholique de Louvain Institut de Recherche Expérimentale et Clinique (IREC) Laboratory of Pediatric Hepatology and Cell Therapy Anatomo-pathology Cliniques Universitaires St-Luc Université Catholique de Louvain

AIM: To investigate the activity and expression of EAAT2 glutamate transporter in both in vitro and in vivo models of cholestasis. METHODS: This study was conducted on human hepatoblastoma HepG2 cell cultures, the liver of bile duct ligated rats and human specimens from cholestatic patients. EAAT2 glutamate transporter activity and expression were analyzed using a substrate uptake assay, immunofluorescence, reverse transcription-polymerase chain reaction, and immunohistochemistry, respectively. RESULTS: In HepG2 cells, cholestasis was mimicked by treating cells with the protein kinase C activator, phorbol 12-myristate 13-acetate. Under such conditions, EAAT2 transporter activity was decreased both at the level of substrate affinity and maximal transport velocity. The decreased uptake was correlated with intracellular translocation of EAAT2 molecules as demonstrated using immunofluorescence. In the liver of bile duct ligated rats, an increase in EAAT2 transporter protein expression in hepatocytes was demonstrated using immunohistochemistry. The same findings were observed in human liver specimens of cholestasis in which high levels of γ-glutamyl transpeptidase were documented in patients with biliary atresia and progressive familial intrahepatic cholestasis type 3. CONCLUSION: This study demonstrates the alteration in glutamate handling by hepatocytes in liver cholestasis and suggests a potential cross-talk between glutamatergic and bile systems.

关键词： glutamate transport Hepatocyte Bile duct ligation

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Neuroprotection of Stilbenes from Leaves of Cajanus cajan against Oxidative Damage Induced by Corticosterone and glutamate in Differentiated PC12 Cells

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Chinese Herbal Medicines 2015年第3期7卷 238-246页

作者： Ya-min Liu Sheng-nan Shen Fang-bo Xia Qi Chang Xin-min Liu Rui-le Pan Institute of Medicinal Plant Development Chinese Academy of Medical Science Peking Union Medical College

Objective To investigate the neuroprotective effects of four stilbenes, namely cajaninstilbene acid （CSA）, Iongistyline A, Iongistyline C, and cajanolactone A, isolated from the leaves of Cajanus cajan. Methods Neuroprotective effects of the four stilbenes were evaluated using rat pheochromocytoma cell line （PC12 cells） damage models induced by corticosterone （Cort） or glutamate. In order to elaborate whether the neuroprotective effects of stilbenes are related to anti-oxidant properties, both oxidant and anti-oxidant parameters were measured. Results The results of MTT assay and LDH release assay demonstrated that the four stilbenes possessed neuroprotective effects. Moreover, the treatment on PC12 cells with Cort or glutamate （Glu） could significantly increase the levels of ROS and MDA with decreasing the activities of SOD and CAT. However, the four tested stilbenes could significantly alleviate such situation by dropping out the levels of ROS and MDA, as well as enhancing the activities of SOD and CAT. Conclusion These results provide a scientific basis for further studies to explore the potential neuroprotective effects on neurodegenerative diseases.

关键词： anti-oxidants Cajanus cajan corticosterone glutamate stilbenes

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