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Introducción: El glutamato monosódico se emplea en humanos desde el pasado siglo como potenciador del sabor. Su inoculación parenteral en murinos durante el período neonatal causa lesiones en varios núcleos hipotalámicos. Objetivo: Describir los efectos del glutamato monosódico sobre el sistema neuroendocrinoinmune en murinos. Metodos: Se realizó una revisión de artículos de libre acceso en las bases de datos PubMed y SciELO entre enero de 2013 y julio de 2020. También se examinó el texto básico de la asignatura Sangre y Sistema Inmune de la carrera de medicina. Desarrollo: Con independencia de su efecto adictivo, varios estudios defienden la inocuidad del glutamato monosódico. Sin embargo, este compuesto puede atravesar la barrera hematoencefálica de neonatos de murinos, y ocasionar trastornos metabólicos, reproductivos y del sistema inmune. Conclusiones: El glutamato monosódico en roedores causa alteraciones en los órganos que integran el suprasistema neuroendocrinoinmune y, por tanto, afecta sus funciones homeostáticas. Los mecanismos patogénicos no se conocen con exactitud.
Introduction: Monosodium glutamate has been used in humans since the last century as a flavor enhancer. Its parenteral inoculation in murine during the neonatal period causes lesions in several hypothalamic nuclei. Objective: To describe the effects of monosodium glutamate on the neuroendocrine immune system in murine samples. Methods: A review of open access articles in the PubMed and SciELO databases was conducted between January 2013 and July 2020. The basic text of the Blood and Immune System course of the medical school was also reviewed. Development: Regardless of its addictive effect, several studies defend the safety of monosodium glutamate. However, this compound can cross the blood-brain barrier of murine neonates, causing metabolic, reproductive and immune system disorders. Conclusions: Monosodium glutamate in rodents causes alterations in the organs that make up the neuroendocrine-immune suprasystem and, therefore, affects their homeostatic functions. The pathogenic mechanisms are not known exactly.
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Objective To investigate the effect of cholecystokinin octapeptide(CCK-8)on glutamate transporter 1(GLT-1)expression in hippocampal astrocytes induced by glutamate(Glu).Methods The mouse hippocampal astrocytes were isolated and the toxicity of CCK-8 at different concentrations on the mouse hippocampal astrocytes was detected.The cells were divided into control group,Glu group,Glu+0.1 μmol/L CCK-8 group,Glu+0.5 μmol/L CCK-8 group and Glu+1.0 μmol/L CCK-8 group.MTT assay was used to detect cell proliferation.Flow cytometry was used to detect cell apoptosis.Biochemical kit was used to detect Glu content in the extracellular supernatant,and qRT-PCR was used to detect the mRNA expression of GLT-1 and glutamate/aspartate transporter(GLAST).The protein expressions of Caspase-3,Bcl-2,GLT-1 and GLAST were detected by Western blotting,and the expression of TNF-α in the cell supernatant was detected by ELISA.Results CCK-8 at different concentrations had no significant effect on the proliferation of mouse hippocampal astrocytes.Compared with the control group,the cell proliferation ability and the expression levels of Bcl-2 protein,GLT-1 and GLAST mRNA and protein in Glu group were significantly decreased(all P＜0.01),the apoptosis rate,extracellular Glu content,Caspase-3 protein expression level in cells and TNF-α level in cell supernatant were significantly increased(all P＜0.01);Compared with the Glu group,the cell proliferation a-bility and the expression levels of Bcl-2 protein,GLT-1 and GLAST mRNA and protein in the Glu+0.5 μmol/L CCK-8 group and Glu+1.0 μmol/L CCK-8 group were significantly increased(all P＜0.05),the apoptosis rate,extracellular Glu content,Caspase-3 protein expression level in cells and TNF-α level in cell supernatant were significantly decreased(all P＜0.01).Con-clusion CCK-8 can inhibit Glu-induced inflammatory response of astrocytes,promote the expression of GLT-1,reduce the con-centration of extracellular Glu,promote cell proliferation and inhibit apoptosis.
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BACKGROUND:Inhibitory control and drug craving are the core elements of evaluating drug withdrawal in methamphetamine addicts,which has attracted much attention in academic circles.As we all know,in order to achieve complete abstinence from drug addiction,the key is to restore the damaged inhibition and control function of drug addicts and effectively reduce the craving for drugs. OBJECTIVE:To systematically analyze the relationship between exercise and methamphetamine abstinence inhibitory control and drug craving,to find out an effective exercise intervention scheme that can promote methamphetamine abstinence,and to further explore the internal mechanism of exercise,in order to provide theoretical support and applied reference for the future use of exercise in drug withdrawal. METHODS:CNKI,WanFang,VIP,Web of Science,and PubMed databases were searched for relevant literature using the keywords of"exercise,physical activity,methamphetamine,inhibitory function,craving,addiction"in Chinese and"sport*,exercise,methamphetamine,drug craving,executive function,addiction"in English.According to the inclusion and exclusion criteria,86 documents were finally included for review. RESULTS AND CONCLUSION:In terms of inhibitory control in methamphetamine abstinent individuals,either acute and long-term moderate-intensity aerobic exercise or acute high-intensity interval training can significantly improve the inhibitory control capacity of methamphetamine abstinent individuals.For long-term aerobic exercise,aerobic group exercise or full-body comprehensive exercise is more effective.If the exercise format is power cycling,it is recommended to increase the frequency of exercise intervention.In terms of the drug craving intensity in methamphetamine abstinent individuals,acute moderate-intensity aerobic exercise and resistance training,as well as long-term moderate-intensity,high-intensity,or progressive load aerobic and resistance training,can effectively reduce the drug craving in methamphetamine abstinent individuals.Exercise exerts intrinsic regulatory effects on methamphetamine-mediated addiction.Exercise can influence the expression of tyrosine hydroxylase in the brain's ventral tegmental area,thereby stimulating the expression of dopamine receptor coupling proteins and promoting dopamine synthesis in the brain's reward regions,thereby compensating for dopamine depletion caused by methamphetamine addiction.Furthermore,exercise can also regulate protein kinase A inhibitors,affecting the protein kinase A signaling pathway mediated by dopamine D1 receptors,by inhibiting protein kinase A,thus affecting cAMP response element-binding protein and regulating methamphetamine addiction.Additionally,exercise can also,at the genetic level,affect the expression of the c-fos gene in the brain's nucleus accumbens region,activate a subset of glutamatergic neurons in this area,generate a rewarding effect,and thus improve methamphetamine addiction.Although current research has confirmed the relationship between exercise and methamphetamine addiction and has clarified the brain mechanisms underlying the effects of exercise,whether there are other brain regulatory pathways for the effects of exercise remains to be explored through more scientifically rigorous animal or human experiments,starting from the cellular or molecular level.
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Most of the current research on depression focuses on neuronal regulation,while the astrocytic mechanism of depression is far from explored.Astrocytes are the most numerous and widely distributed glial cells in the central nervous system.With a complex structural morphology,astrocytes play an important role in a variety of neuropsychiatric disorders by interacting with neuronal synapses,vasculature and other glial cells.Recent studies have shown that astrocytes may be involved in depression by regulating monoamine transmitters,glutamate cycle,synaptic plasticity,energy metabo-lism,and neuroinflammation.This review is intended to inspire new ideas for the treatment of depres-sion and the development of novel drugs based on astrocyte regulation.
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Objective To observe the effects of electroacupuncture(EA)on glutamate(Glu),metabotropic glutamate receptor 2/3(mGluR2/3)and apoptosis related proteins expression in hippocampus in rats with acute myocardial ischemia(AMI);To explore the mechanism of EA against AMI.Methods Totally 50 SD rats were randomly divided into sham-operation group,model group,EA group and inhibitor group,with 10 rats in each group.Except for the sham-operation group,the rats were treated with ligation at the left anterior descending coronary artery to establish AMI model.The rats in the EA group was treated with EA at"Shenmen"and"Tongli",30 minutes each time,once a day for 3 consecutive days.The rats in the inhibitor group were treated with injection of LY341459 via the lateral ventricle 30 min after modeling.HE staining was used to observe myocardial tissue morphology,and ELISA was used to detect Caspase-3 activity in myocardial tissue and Glu content in hippocampal tissue,immunofluorescence staining was used to detect mGluR2/3 expression in hippocampal tissue,TUNEL staining was used to detect apoptosis in hippocampal tissue cells,Western blot was used to detect the expressions of PI3K,Akt,and Caspase-3 protein in hippocampal tissue.Results Compared with the sham-operation group,the myocardial cells of the model group rats showed sparse and swelling with severe infiltration of inflammatory cells;the activity of Caspase-3 in myocardial tissue significantly increased,and the Glu content,positive expression of mGluR2/3,number of apoptotic cells in hippocampal tissue significantly increased(P<0.01),and the expressions of PI3K and Akt proteins in hippocampal tissue were significantly decreased,while the expression of Caspase-3 protein significantly increased(P<0.01).Compared with the model group,myocardial cell edema and inflammatory cell infiltration were reduced in the EA group and inhibitor group,the activity of Caspase-3 in myocardial tissue was significantly decreased,the Glu content,positive expression of mGluR2/3,and number of apoptotic cells in hippocampal tissue were significantly reduced(P<0.01),the expressions of PI3K and Akt proteins in hippocampal tissue significantly increased,while the expression of Caspase-3 protein significantly decreased(P<0.01).Conclusion EA can improve myocardial injury in AMI rats,and its mechanism may be related to activation of PI3K/Akt signaling pathway,inhibition of hippocampal mGluR2/3 overexpression,reduction of Glu accumulation,inhibition of apoptosis of hippocampal neurons and reduction of neurotoxicity.
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Objective To explore the correlation of serum glutamate(Glu)and gamma-aminobutyric acid(GABA)levels with clinical symptoms in chronic schizophrenia patients,and to assess their diagnostic value for cognitive impairment.Methods A total of 92 patients with chronic schizophrenia and another 80 healthy individuals in Wuhan Mental Health Center/Wuhan Hospital for Psychotherapy from January 2021 to July 2022 were enrolled as study group and control group,respectively.The patients in the study group were divid-ed into the cognitive impairment group(44 cases)and the cognitive normal group(48 cases)according to Montreal Cognitive Assessment Scale(MoCA).Clinical symptoms were assessed by using Positive and Nega-tive Syndrome Scale(PANSS).MoCA was used to evaluate the cognitive function.The levels of Glu and GA-BA in plasma were determined by high-performance liquid chromatography/electrospray tandem mass spec-trometry.The scores of PANSS and MoCA as well as serum levels of Glu and GABA were compared between two groups.Then the correlation of serum Glu and GABA levels with clinical symptoms and the diagnostic value for cognitive impairment in the patients in the study group were investigated.Results The Glu level in the study group was higher than that in the control group,and the GABA level was lower than that in the con-trol group(P＜0.05).The serum Glu levels in both the cognitive impairment group and the cognitive normal group were higher than the normal range,and the Glu level in the cognitive impairment group was higher than that in the cognitive normal group(P＜0.05).The serum GABA levels in both the cognitive impairment group and the cognitively normal group were lower than the normal range,and the GABA level in the cogni-tive impairment group was lower than that in the cognitive normal group(P＜0.05).In the study group,ser-um Glu level was positively correlated with negative,positive,general psychopathological symptom scores,and overall score in PANSS(P＜0.05),while GABA level was negatively correlated with negative,positive,gener-al psychopathological symptom scores,and overall score in PANSS(P＜0.05).The sensitivity of the single and combined detection of serum Glu and GABA for the diagnosis of cognitive impairment in patients with chronic schizo-phrenia was 77.3％,72.7％and 93.2％,respectively,and the specificity was 72.9％,72.9％,and 75.0％,respec-tively,and the area under the curve was 0.778,0.769,and 0.868,respectively.Conclusion Serum Glu level in patients with chronic schizophrenia is higher than that in healthy individuals,while GABA level is lower than that in healthy individuals,and the above two indicators are correlated with PANSS score,which have high value in diagnosing cognitive impairment and could be used as effective biological indicators to help clinical doctors judge patients'cognitive function.
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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons. ALS patients develop progressive muscle atrophy, muscle weak and paralysis, finally died of respiratory failure. ALS is characterized by fast aggression and high mortality. What' s more, the disease is highly heterogeneous with unclear pathogenesis and lacks effective drugs for therapy. In this review, we summarize the main pathological mechanisms and the current drugs under development for ALS, which may provide a reference for the drug discovery in the future.
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Objective To observe the expression and localization of group Ⅰ metabotropic glutamate receptors (mGluR1/ 5) in rat superior cervical ganglion (SCG) and the effect of chronic intermittent hypoxia (CIH) on mGluR1/ 5 protein level. Methods Twelve male SD rats were randomly divided into control group(Ctrl)and CIH group(CIH), 6 rats in each group. After 6 weeks of modeling, the effect of CIH on mGluR1/ 5 protein level was detected by Western blotting, the expression and distribution of mGluR1/ 5 in SCG were detected by immunohistochemistry and double-immunofluorescent staining. Results mGluR1/ 5 was expressed in rat SCG. mGluR1 was distributed in neurons and small intensely fluorescent (SIF) cells, but not in satellite glial cells (SGCs), nerve fibers and blood vessels, whereas mGluR5 was mainly distributed in nerve fibers and a little in neurons, but not in SGCs, SIF cells and blood vessels. CIH increased the protein levels of mGluR1/ 5 (P<0. 01) in rat SCG. Conclusion Both mGluR1 and mGluR5 are expressed in the rat SCG, but their distribution are different, and the increased protein levels of both may be involved in CIH-induced hypertension.
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Background: Sodium mono glutamate (MSG), the sodium salt of glutamic acid, is a food flavoring agent that is widely used in many countries. Pomegranate is used as a traditional medication in numerous countries, it is planted in Asian countries, Mediterranean countries and the U.S.A. Aim of the work: The present study aimed to detect structural and functional changes in adult rat kidney tissue treated with sodium mono glutamate, and the possible protective effect of pomegranate on the kidney treated with MSG. Materials and Methods: This study was done by using 60 adult Wistar Albino rats of both sexes were divided into three equal groups: Group I (control group), Group II (sodium mono glutamate treated group), and Group III (combined MSG and pomegranate treated group) Doses were given once daily for 8 weeks every day. At the end of the treatment period, blood samples collected from each rat were used for measuring the values of urea and creatinine. Also animals of the different groups were sacrificed at the end of the experiment, quickly dissected and the kidneys were removed and stained with hematoxylin and eosin (H&E) for the histological examination by light microscopy, other tissue sections were evaluated using a transmission electron microscope. Both were used to examine the effect of sodium mono glutamate on cortex of the kidneys of albino rats ,compared with control group and the combined MSG and pomegranate group. Results: There was a major rise in blood urea level and blood creatinine level in sodium mono glutamate treated group in contrast to the control group. There was a significant reduction in blood urea level and blood creatinine level in combined sodium mono glutamate and pomegranate treated group in comparison to MSG treated group. Examination of kidney tissue of rats treated with sodium mono glutamate (Group. II) showed damaging changes of its structure. The glomerulus had markedly widened blood capillaries with thickened filtration membrane. The epithelial tubular cells had marked degenerative changes. Examination of rats kidney tissue treated with sodium mono glutamate and pomegranate (Group III) revealed improvement of the lesions in the glomeruli and renal tubules. Conclusion: Pomegranate protected the kidneys and restricted the histological and functional alterations caused by sodium mono glutamate, and thus, there is an advantage of usage of pomegranate with sodium mono glutamate.
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Este estudio tuvo como objetivo demostrar la existencia de variaciones morfológicas en el tejido conectivo de la glándula submandibular de ratas obesas expuestas a glutamato monosódico (GMS). Se utilizaron 12 ratas Sprague Dawley machos recién nacidas (6 ratas para el grupo 1, control; 6 ratas para el grupo 2 (GMS), 4 mg/g de glutamato monosódico de peso (5 dosis) mantenidas por 16 semanas respectivamente con una dieta y agua ad libitum. En el estudio se realizó un análisis estereológico e histológico, demostrándose una variación en el tejido conectivo presentando una disminución del volúmen glandular, mayor fibrosis, y disminución de adipocitos a nivel periférico siendo reemplazado por tejido rico en colágeno. Los vasos sanguíneos observados a nivel estereológico no presentan mayores cambios en cuanto a volumen, superficie y área.
SUMMARY: This study aims to demonstrate the existence of morphological variations in the connective tissue of the submandibular gland of obese rats exposed to MSG. Twelve male newborn Sprague Dawley rats were used (6 rats for group 1, control; 6 rats for group 2 (MSG), 4 mg/g of monosodium glutamate of weight (5 doses) maintained for 16 weeks respectively with a diet and water ad libitum. In the study, a stereological and histological analysis was carried out, demonstrating a variation in the connective tissue, presenting a decrease in the glandular volume, greater fibrosis, and a decrease in adipocytes at the peripheral level, being replaced by tissue rich in collagen. Blood cells observed at the stereological level do not present major changes in terms of volume, surface and area, but in the histological study greater vascularization is observed.
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Animals , Male , Rats , Sodium Glutamate/administration & dosage , Submandibular Gland/drug effects , Obesity , Sodium Glutamate/pharmacology , Blood Vessels/drug effects , Body Weight , Fibrosis , Rats, Sprague-Dawley , Connective Tissue/drug effects , Animals, NewbornABSTRACT
This study aims to explore the effect of preventive administration of Yigong Powder on the learning and memory abilities of the mouse model of aging induced by D-galactose and decipher the underlying mechanism, so as to provide a basis for the application of Yigong Powder in the prevention and treatment of cognitive decline. Forty KM mice were randomized into control, model, donepezil(1.5 mg·kg~(-1)), and high-dose(7.5 g·kg~(-1)) and low-dose(3.75 g·kg~(-1)) Yigong Powder groups. The mice in other groups except the control group were injected with D-galactose(200 g·kg~(-1)) at the back of the neck for the modeling of aging. At the same time, the mice were administrated with corresponding drugs by gavage for one month. Morris water maze was used to examine the learning and memory abilities of the mice. Hematoxylin-eosin staining was employed to observe the pathological and morphological changes of the hippocampus. The immunofluorescence assay was employed to detect the expression of ionized calcium-binding adapter molecule 1(IBA1), glial fibrillary acidic protein(GFAP), chemokine C-X-C-motif ligand 12(CXCL12), chemokine C-X-C-motif receptor 4(CXCR4) in the hippocampus and observe the positional relationship between IBA1, GFAP, and CXCR4. Western blot was employed to determine the protein levels of extracellular regulated kinase(ERK), p-ERK, and tumor necrosis factor receptor 1(TNFR1). Enzyme-linked immunosorbent assay was employed to measure the levels of glutamate and tumor necrosis factor(TNF-α) in the brain tissue and the level of TNF-α in the serum and spleen. Yigong Powder significantly shortened the escape latency, increased the times crossing platforms, and prolonged the cumulative time in quadrants of the aging mice. It alleviated the nerve cell disarrangement, increased intercellular space, and cell degeneration or death in the hippocampus and reduced the pathology score of the damaged nerve. Moreover, Yigong Powder reduced the positive area of IBA1 and GFAP, reduced the levels of TNF-α in the brain tissue, serum, and spleen, and decreased spleen index. Furthermore, Yigong Powder decreased the average fluorescence intensity of CXCL12 and CXCR4, reduced CXCR4-positive astrocytes and microglia, down-regulated the protein levels of p-ERK/ERK and TNFR1, and lowered the level of glutamate in the brain tissue. This study showed that the preventive administration of Yigong Powder can ameliorate the learning and memory decline of the D-galactose-induced aging mice by regulating the immune function of the spleen and the CXCL12/CXCR4 signaling in the brain to reduce glutamate release. However, the mechanism of Yigong San in preventing and treating dementia via regulating spleen and stomach function remains to be studied.
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Mice , Animals , Powders , Receptors, Tumor Necrosis Factor, Type I , Glutamic Acid , Tumor Necrosis Factor-alpha/metabolism , Galactose/adverse effects , Disease Models, Animal , Cognitive Dysfunction/prevention & control , Chemokines , Drugs, Chinese HerbalABSTRACT
Objective:To investigate the expression of phosphorylated glutamate receptor 2[p-GluR2(S880)]in oligodendrocyte precursor cells(OPCs)of mice model of hypoxic ischemic brain injury(HIBI).Methods:The HIBI model of C57BL/6 neonatal mice was established by right common carotid artery ligation and hypoxia for 90 min.The anxiety-like behavior of the mice was evaluated by elevated plus maze(EPM)and open field test(OFT).The expres-sion of p-GluR2(S880),oligodendrocyte marker 4(O4)and myelin basic protein(MBP)in brain tissue of HIBI model mice was detected by immunofluorescence staining.What's more,the expression levels of p-GluR2(S880)and MBP were detected by Western Blot.Results:Compared with sham operation group,there were significant anxiety-like behaviors 90 days after HIBI operation(P＜0.05).The expression of MBP protein decreased significantly in 14 and 28 days after HIBI operation.The expression of p-GluR2(S880)protein was up-regulated at all time points after HIBI op-eration(P＜0.05),and the number of O4 and p-GluR2(S880)double positive cells in brain tissue of HIBI group was significantly increased(P＜0.05).Conclusion:The up-regulation of p-GluR2(S880)expression in OPCs may lead to myelination disorder in HIBI model mice.
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Objective:To investigate the neurobiochemical metabolites of caudate nucleus and thalamus in patients with obsessive-compulsive disorder and their relationship with obsessive-compulsive symptoms.Methods:From April 2019 to January 2022 in Beijing Anding Hospital, totally 25 untreated patients with obsessive-compulsive disorder were recruited, and 20 healthy controls matched with gender, age and educational background were recruited for the study.The maps of neurobiochemical metabolites of patients and normal controls were collected by hydrogen proton magnetic resonance spectroscopy.With bilateral caudate nucleus and thalamus as brain regions of interest.The relative concentrations of N-acetylaspartic acid (NAA), glutamic acid (Glu) and γ-aminobutyric acid (GABA) were fitted by LCModel software.At the same time, the clinical symptoms of patients were evaluated with Yale-Brown obsessive-compulsive scale (Y-BOCS) and Hamilton anxiety scale (HAMA). SPSS 20.0 software was used for statistical analysis.Independent double sample t-test was used to compare the differences of different nerve biochemical metabolite concentrations between patients with obsessive-compulsive disorders and healthy controls.Pearson correlation analysis was used to explore the correlation between biochemical metabolite concentrations and clinical symptoms. Results:The Glu concentration in the left thalamus of patients with obsessive-compulsive disorder (3.97±0.41) was higher than that of the control group (3.66±0.55)( t=-2.11, P<0.05), while the NAA concentration was (4.87±0.47)lower than that of the control group (5.15±0.44)( t=2.05, P<0.05). The GABA concentrations in the right caudate nucleus (0.50±0.18) and thalamus (0.80±0.19) were lower than those in the control group ((0.63±0.23), (0.96±0.24))( t=2.08, 2.36, both P<0.05). Pearson correlation analysis showed that the Glu concentration in the left caudate nucleus of patients with obsessive-compulsive disorder was positively correlated with the total score of Y-BOCS( r=0.46, P<0.05). Spearman correlation analysis showed that Glu concentration in the right caudate nucleus was positively correlated with the total score of HAMA in patients with obsessive-compulsive disorder ( r=0.46, P<0.05). Conclusion:NAA, Glu and GABA metabolism in caudate nucleus and thalamus are abnormal in patients with obsessive-compulsive disorder, and Glu concentration is positively correlated with the severity of obsessive-compulsive and anxiety symptoms.
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Abnormal homeostasis of glutamate(Glu)and γ-aminobutyric acid(GABA)in the brain is one of pathophysiological mechanisms of brain dysfunction in major depressive disorder(MDD).Neurotransmitters play an important role in maintaining chemical balance in the brain,and pharmacological and non-pharmacological therapies based on resetting excitation-inhibitory neurotransmitter system rebalancing are of interest.Studies based on magnetic resonance spectroscopy(MRS)have shown a homeostasis imbalance of Glu and GABA in the brain of MDD patients.Pharmacological therapies such as ketamine,selective serotonin reuptake inhibitors,and other novel receptor modulators and non-pharmacological therapies such as repetitive transcranial magnetic stimulation,electroconvulsive therapy,and physical exercise can target on the regulation of neurotransmitter levels.Abnormal homeostasis of Glu and GABA provides theoretical support for revealing pathophysiologic mechanisms of MDD,exploring neurotransmitter biomarkers,guiding clinical practice and facilitating personalized treatment.
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Depression is one of the most common psychiatric disorders with high prevalence, disability and relapse rates, and its etiology and pathogenesis are complex and still not fully understood. Neurotransmitters play a key role in maintaining chemical homeostasis in brain, and many studies have shown a strong link between neurotransmitters and the development and treatment of depression in recent years. Therefore, studying the neurotransmitters associated with depression has the potential to provide research targets and ideas for the pathogenesis and treatment strategies of depression. This paper reviews the recent domestic and foreign research results on neurotransmitter function and the pathogenesis of depression, aiming to analyze the in-depth relationship between neurotransmitter function and the pathogenesis of depression, and provide research ideas for the follow-up ex-ploration of the pathogenesis and diagnosis and treatment strategies of depression.
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L-glutamic acid is the world's largest bulk amino acid product that is widely used in the food, pharmaceutical and chemical industries. Using Corynebacterium glutamicum G01 as the starting strain, the fermentation by-product alanine content was firstly reduced by knocking out the gene encoding alanine aminotransferase (alaT), a major by-product related to alanine synthesis. Secondly, since the α-ketoglutarate node carbon flow plays an important role in glutamate synthesis, the ribosome-binding site (RBS) sequence optimization was used to reduce the activity of α-ketoglutarate dehydrogenase and enhance the glutamate anabolic flow. The endogenous conversion of α-ketoglutarate to glutamate was also enhanced by screening different glutamate dehydrogenase. Subsequently, the glutamate transporter was rationally desgined to improve the glutamate efflux capacity. Finally, the fermentation conditions of the strain constructed using the above strategy were optimized in 5 L fermenters by a gradient temperature increase combined with a batch replenishment strategy. The glutamic acid production reached (135.33±4.68) g/L, which was 41.2% higher than that of the original strain (96.53±2.32) g/L. The yield was 55.8%, which was 11.6% higher than that of the original strain (44.2%). The combined strategy improved the titer and the yield of glutamic acid, which provides a reference for the metabolic modification of glutamic acid producing strains.
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Glutamic Acid , Corynebacterium glutamicum/genetics , Ketoglutaric Acids , Metabolic Engineering , AlanineABSTRACT
Objective:To evaluate the role of Homer1a/metabotropic glutamate receptor 5 (mGluR5) signaling pathway in sleep deprivation-induced cognitive dysfunction in aged rats.Methods:One hundred and four SPF healthy male Sprague-Dawley rats, aged 22-24 months, weighing 320-360 g, were divided into 4 groups ( n=26 each) using a random number table method: normal control group (group Control), sleep deprivation+ vehicle group (group SD+ Vehicle), sleep deprivation+ mGluR5 forward allosteric agent CDPPB group (group SD+ CDPPB), and sleep deprivation+ mGluR5 antagonist MPEP group (group SD+ MPEP). A 48-h sleep deprivation model was developed by sleep-deprived rod method. At the beginning of developing the model and 24 h after developing the model, CDPPB 10 mg/kg, MPEP 10 mg/kg and the equal volume of 1% Tween 80 were intraperitoneally injected in group SD+ CDPPB, group SD+ MPEP and group SD+ Vehicle, respectively.Morris water maze and novel object recognition tests were conducted to evaluate cognitive function after development of the model. The expression of Homer1a and mGluR5 in the hippocampus was detected by Western blot, the dendritic spine density in the hippocampal CA1 region was detected by Golgi staining, and the field excitatory postsynaptic potential (fEPSP) slope in the hippocampal CA1 region was detected by isolated electrophysiology. Results:Compared with Control group, the number of crossing the original platform, time of staying at the target quadrant, and novel object recognition index at 1 and 24 h after training were significantly decreased, the expression of Homer1a in the hippocampus was up-regulated, the expression of mGluR5 in the hippocampus was down-regulated, and the density of dendritic spine and fEPSP slope in the hippocampal CA1 region were decreased in group SD+ Vehicle ( P<0.05). Compared with group SD+ Vehicle, the number of crossing the original platform, time of staying at target quadrant, and novel object recognition index at 1 and 24 h after training were significantly increased, the expression of mGluR5 in hippocampus was up-regulated, and the density of dendritic spines and fEPSP slope in the hippocampal CA1 region were increased in group SD+ MPEP( P<0.05), and no statistically significant change was found in the parameters mentioned above in group SD+ CDPPB ( P>0.05). Conclusions:Sleep deprivation impairs the synaptic plasticity of hippocampal neurons by regulating Homer1a/mGluR5 signaling pathway, and thus mediating the process of cognitive dysfunction in aged rats.
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Objective:To evaluate the role of activation of vesicular glutamate transporter 2 (VGLUT2) neurons in vagal nodose ganglion in dexmedetomidine-caused bradycardia in mice.Methods:Ninety-six SPF healthy male VGLUT2-cre mice, aged 10 weeks, weighing 20-25 g, were divided into 6 groups ( n=16 each) by the random number table method: normal saline control group (NS group), dexmedetomidine group (Dex group), viral control + chemogenetic control + dexmedetomidine group (eGFP-NS+ Dex group), viral transfection + chemogenetic control + dexmedetomidine group (hM4Di-NS+ Dex group), viral control + chemogenetic inhibition + dexmedetomidine group (eGFP-CNO+ Dex group) and viral transfection + chemogenetic inhibition + dexmedetomidine group (hM4Di-CNO+ Dex group). Dexmedetomidine 100 μg/kg was intraperitoneally injected in Dex group. The equal volume of normal saline was intraperitoneally injected in NS group. AAV2/9-hSyn-DIO-hM4Di-eGFP was injected in the right nodose ganglion in hM4Di-NS+ Dex group and hM4Di-CNO+ Dex group, and AAV2/9-hSyn-DIO-eGFP was injected in the right nodose ganglion in eGFP-NS+ Dex group and eGFP-CNO+ Dex group, allowing the virus expression for 21 days. On the 22nd day after virus injection, clozapine-n-oxide (CNO) 5 mg/kg was intraperitoneally injected in hM4Di-CNO+ Dex group and eGFP-CNO+ Dex group, the equal volume of normal saline was intraperitoneally injected in hM4Di-NS+ Dex group and eGFP-NS+ Dex group, 1 h later the efficacy of CNO reached the peak, and then dexmedetomidine 100 μg/kg was intraperitoneally injected. The respiratory rate, heart rate, SpO 2 and discharge frequency of the right vagal nodose ganglion were synchronously measured by multi-channel electrophysiology in vivo. The expression of phosphorylated extracellular signal-regulated kinase (pERK) and VGLUT2 and co-expression of pERK and VGLUT2 in the right vagal nodose ganglion were detected by immunofluorescence assay. Results:Compared with NS group, the percentage of heart rate variation and neuron firing frequency after administration were significantly increased, and pERK expression was up-regulated in the other five groups ( P<0.05). Compared with Dex group, the percentage of heart rate variation and neuron firing frequency after administration were significantly decreased, and pERK expression was down-regulated in hM4Di-CNO+ Dex group, and no significant change was found in the parameters mentioned above in hM4Di-NS+ Dex group, eGFP-NS+ Dex group and eGFP-CNO+ Dex group ( P>0.05). Compared with hM4Di-CNO+ Dex group, the percentage of heart rate variation and neuron firing frequency after administration were significantly increased, and pERK expression was up-regulated in eGFP-CNO+ Dex group ( P<0.05). There was no significant difference in the percentage of respiratory variation and SpO 2 among the six groups ( P>0.05). The expression of VGLUT2-positive neurons was abundant in nodose ganglia, and the co-expression rate of pERK and VGLUT2 was nearly 90%. The co-expression rate of pERK and VGLUT2 decreased to about 30% after inhibition of VGLUT2 neurons in ganglion. Conclusions:The mechanism by which dexmedetomidine causes bradycardia is associated with activation of VGLUT2 neurons in vagal nodose ganglia in mice.
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Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a specific subtype of the stiff-person syndrome, which is rare and difficult to diagnose clinically. A case of PERM in a 66-year-old female with a fluctuating progressive course was reported in this article. She had increased facial muscle tone, pruritus and sensory hypersensitivity mainly in the head and neck, medullary involvement syndrome and bilateral lower limb rigidity as the main clinical manifestations, and a previous history of pulmonary malignancy, thymoma, typeⅠ diabetes and Hashimoto′s thyroiditis. The patient′s serum and cerebrospinal fluid were positive for anti-glutamic acid decarboxylase antibody. The electromyogram showed a large number of motor unit potentials in the trunk and proximal extremities in the quiet state, which were significantly enhanced during spastic episodes, consistent with the electromyographic manifestations of stiff-person syndrome. The final diagnosis was PERM, and immunotherapy including gamma globulin and hormone responded well. PERM is a rare neurological autoimmune disease with atypical early symptoms, which can be easily misdiagnosed, and it requires attention to avoid delaying the diagnosis.
ABSTRACT
ObjectiveTo explore the possible mechanism of Yudian Decoction （愈癫汤） in the treatment of schizophrenia. MethodTwenty male offspring from 5 normal female 17-day-pregnant SD rats were selected as blank group. Fifteen female 17-day-pregnant SD rats were injected intraperitoneally with methyl azomethine acetate （MAM） 25 mg/kg， and the male offspring simulated the neurodevelopmental abnormality to establish a rat model of schizophrenia. Sixty successfully-modeled rats were randomly divided into 20 rats in the model group， 20 rats in the Yudian Decoction group and 20 risperidone group. After 3 days of adaptive cage feeding， the rats in the Yudian Decoction group were gavaged with 1.54 g/（kg·d） of Yudian Decoction， the risperidone group was gavaged with 0.24 mg/（kg·d） of risperidone capsule， while the blank group and the model group were gavaged with 6.7 ml/（kg·d） of distilled water， once a day， for 14 consecutive days. Sample was collected on the day after the last gavage. The expression of glutamate receptor （GluR） and γ-aminobutyric acid receptor subunit α1 （GABAARα1）-positive neurons in the hippocampus and prefrontal cortex were detected by immunofluorescence， and the positive rate was calculated； the expression of small clear proteins （PVs） in the hippocampal CA1 region and the medial prefrontal cortex was detected by immunohistochemistry； The expression of glutamic acid decarboxylase 65 （GAD65） and glutamic acid decarboxylase 67 （GAD67） proteins and mRNAs in the hippocampus and prefrontal cortex were detected by immunoblotting and reverse transcription PCR. ResultCompared with the blank group， the positive rate of GluR in hippocampal area and prefrontal cortex of rats in the model group increased， the positive rate of GABAARα1 in hippocampal area decreased， the PV optical density value in hippocampal CA1 area and medial prefrontal cortex decreased， and the expression of GAD65， GAD67 proteins and mRNA in hippocampal area and prefrontal cortex decreased （P＜0.05 or P＜0.01）. Compared with the model group， GluR positivity rate in hippocampus and prefrontal cortex of risperidone group and Yudian Decoction decreased， GABAARα1 positivity rate in hippocampus increased， PV optical density value in hippocampus CA1 area and medial prefrontal cortex increased， and GAD65， GAD67 proteins and mRNA expression in hippocampus and prefrontal cortex increased （P＜0.05 or P＜0.01）. Compared with the risperidone group， the positive rate of GluR in hippocampus and prefrontal cortex and GABAARα1 in hippocampus in the Yudian Decoction group was reduced， the PV optical density value of hippocampal CA1 area was increased， the protein and mRNA expression of GAD67 in hippocampus area was elevated， and the protein expression of GAD65 in prefrontal cortex was reduced （P＜0.05）. ConclusionYudian Decoction may improve the pathological process of schizophrenia by regulating key regulators of glutamate/γ-aminobutyric acid （Glu/GABA） metabolic balance in the hippocampus and prefrontal cortex and maintaining the balance between neuronal excitation and inhibition.