Increase In Glutamate Levels Research Articles

Role of Glutamine Synthetase on Vascular Permeability in Gliomas.

This study aimed to investigate the effect and underlying mechanism of inhibiting glutamine synthetase (GS) on the vascular permeability of gliomas. C6 glioma rat models were randomly divided into control and L-methionine sulfoximine (MSO) treatment groups. MSO was intraperitoneally injected once every other day for a total of three injections in the MSO group. We assessed the effect of MSO on tumor vascular permeability by tail vein injection of Evans blue dye. GS activity, glutamate (Glu) concentration, glutamine (Gln) concentration, and arginine concentration in tumor tissues were measured using the corresponding kits. qPCR experiments were then conducted to examine the effect of glutamate concentration on N-methyl-D-aspartate (NMDA) receptor expression. Finally, the nitric oxide synthase (NOS) assay kit and the nitric oxide (NO) assay kit were employed to detect NOS activity and NO concentration changes, respectively. Increased glioma tumor vascular permeability was observed after intraperitoneal injection of MSO; MSO acted as an inhibitor of GS, leading to a decrease in GS activity; increased glutamate levels caused activation of NMDA receptors and further activation of NOS; additionally, elevated NO levels were detected in association with an increase in arginine and NOS. Inhibiting GS results in increased vascular permeability in gliomas, which is associated with elevated NO levels and the vasodilatory effects of NO.

Therapeutic potential of oleanolic acid in modulation of PI3K/Akt/mTOR/STAT-3/GSK-3β signaling pathways and neuroprotection against methylmercury-induced neurodegeneration

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that gradually deteriorates motor neurons, leading to demyelination, muscle weakness, and eventually respiratory failure. The disease involves several pathological processes, such as increased glutamate levels, mitochondrial dysfunction, and persistent neuroinflammation, often exacerbated by environmental toxins like mercury. This study explores the therapeutic potential of Olea europaea active phytoconstituents oleanolic acid (OLA) against ALS by targeting the overactivated PI3K/Akt/mTOR/STAT-3/GSK-3β signalling pathways. Methods involved in-silico studies, in vitro and in vivo experiments in which varying doses of methylmercury 5 mg/kg, p.o. and OLA (100 and 200 mg/kg, i.p.) were administered to rats for 42 days. Behavioural assessments, gross morphological, histopathological, and neurochemical parameters were measured in cerebrospinal fluid (CSF), blood plasma, and brain homogenates (cerebral cortex, hippocampus, striatum, midbrain, cerebellum) along with complete blood count (CBC) analysis. Results revealed OLA's significant neuroprotective properties. OLA effectively modulated targeted pathways, reducing pro-inflammatory cytokines, restoring normal levels of myelin basic protein (MBP) and neurofilament light chain (NEFL), and reducing histopathological changes. Gross pathological studies indicated less tissue damage, while CBC analysis showed improved hematology parameters. Additionally, the combination of OLA and edaravone (10 mg/kg, i.p.) demonstrated enhanced efficacy, improving motor functions and extending survival in ALS model rats. In conclusion, OLA exhibits significant therapeutic potential for ALS, acting as a potent modulator of key pathological signaling pathways. The findings suggest the feasibility of integrating OLA into existing treatment regimens, potentially improving clinical outcomes for ALS patients. However, further research must validate these findings in human clinical trials.

A eficácia do canabidiol no tratamento de transtornos mentais: Uma revisão sistemática de ensaios clínicos randomizados duplo-cegos

INTRODUCTION: The therapeutic application of cannabidiol (CBD) is gaining interest due to the growing body of evidence supporting its use in the treatment of mental disorders. OBJECTIVES: To develop a systematic review to evaluate the scientific evidence supporting the use of CBD in the treatment of psychiatric disorders. METHODS: Only double-blind randomized clinical trials were used. The search for scientific evidence was carried out in the PubMed and VHL databases, with the descriptors "cannabidiol" and "mental disorders". Between 2020 and 2022, 219 articles were found in PubMed and 79 in the VHL. Review articles, observational studies, manuscripts, repeated articles, and articles that did not focus on the treatment of mental disorders by the use of cannabidiol were excluded. Thus, 10 relevant studies remained for the present systematic review. RESULTS: Of the 10 articles selected, 90% presented positive results for the use of CBD in the treatment of various mental disorders. Among them, there was a higher prevalence of drug use for the treatment of psychosis, anxiety and behavioral mechanisms; evidencing its usefulness and benefits. It was observed that in cases of psychosis, CBD significantly increased glutamate levels in the left hippocampus of patients, proving its effectiveness. In research involving behavioral mechanisms, it was possible to verify that the use of CBD linearly decreased the levels of cortisol linked to stress in the patient's body, evidencing its therapeutic capacity. CONCLUSION: The use of CBD was useful to relieve the symptoms of some mental disorders, such as psychosis, anxiety, schizophrenia, autism, behavioral problems and stress. In addition, research has still shown uncertain and sometimes even contradictory results, which reinforces the need for more research on the action of this drug in the treatment of mental disorders.

Discovery of the Inhibitor Targeting the SLC7A11/xCT Axis through In Silico and In Vitro Experiments.

In the development and progression of cervical cancer, oxidative stress plays an important role within the cells. Among them, Solute Carrier Family 7 Member 11 (SLC7A11/xCT) is crucial for maintaining the synthesis of glutathione and the antioxidant system in cervical cancer cells. In various tumor cells, studies have shown that SLC7A11 inhibits ferroptosis, a form of cell death, by mediating cystine uptake and maintaining glutathione synthesis. Additionally, SLC7A11 is also involved in promoting tumor metastasis and immune evasion. Therefore, inhibiting the SLC7A11/xCT axis has become a potential therapeutic strategy for cervical cancer. In this study, through structure-based high-throughput virtual screening, a compound targeting the SLC7A11/xCT axis named compound 1 (PubChem CID: 3492258) was discovered. In vitro experiments using HeLa cervical cancer cells as the experimental cell model showed that compound 1 could reduce intracellular glutathione levels, increase glutamate and reactive oxygen species (ROS) levels, disrupt the oxidative balance within HeLa cells, and induce cell death. Furthermore, molecular dynamics simulation results showed that compound 1 has a stronger binding affinity with SLC7A11 compared to the positive control erastin. Overall, all the results mentioned above indicate the potential of compound 1 in targeting the SLC7A11/xCT axis and treating cervical cancer both in vitro and in silico.

Imbalance in Unc80 RNA Editing Disrupts Dynamic Neuronal Activity and Olfactory Perception.

A-to-I RNA editing, catalyzed by the ADAR protein family, significantly contributes to the diversity and adaptability of mammalian RNA signatures, aligning with developmental and physiological needs. Yet, the functions of many editing sites are still to be defined. The Unc80 gene stands out in this context due to its brain-specific expression and the evolutionary conservation of its codon-altering editing event. The precise biological functions of Unc80 and its editing, however, are still largely undefined. In this study, we first demonstrated that Unc80 editing occurs in an ADAR2-dependent manner and is exclusive to the brain. By employing the CRISPR/Cas9 system to generate Unc80 knock-in mouse models that replicate the natural editing variations, our findings revealed that mice with the "gain-of-editing" variant (Unc80G/G) exhibit heightened basal neuronal activity in critical olfactory regions, compared to the "loss-of-editing" (Unc80S/S) counterparts. Moreover, an increase in glutamate levels was observed in the olfactory bulbs of Unc80G/G mice, indicating altered neurotransmitter dynamics. Behavioral analysis of odor detection revealed distinctive responses to novel odors-both Unc80 deficient (Unc80+/-) and Unc80S/S mice demonstrated prolonged exploration times and heightened dishabituation responses. Further elucidating the olfactory connection of Unc80 editing, transcriptomic analysis of the olfactory bulb identified significant alterations in gene expression that corroborate the behavioral and physiological findings. Collectively, our research advances the understanding of Unc80's neurophysiological functions and the impact of its editing on the olfactory sensory system, shedding light on the intricate molecular underpinnings of olfactory perception and neuronal activity.

Plasma amino acids spectrum and Holter ECG monitoring indexes in coronary artery disease patients with atrial fibrillation

The research was conducted with the aim of establishing a connection between plasma amino acid peculiarities and Holter ECG monitoring indexes in Coronary Artery Disease (CAD) and Atrial Fibrillation (AF) patients. 300 patients were examined divided into 3 groups: I – 149 patients with CAD without arrhythmias, II – 124 patients with CAD and AF paroxysm, and the Control Group (CG) – 27 patients without CAD and arrhythmias. Holter ECG monitoring was performed for the patients with AF within 24 hours after sinus rhythm restoration, and for the patients without AF on the first day of observation. Plasma AA level was detected by the method of ion exchange liquid column chromatography. It was established that there is a significant increase glutamate and Branched-Chain Amino Acids (BCAA) levels in patients of the II group, and significant depletion in glycine levels comparison with the I group patients (p<0.05). In the II group patients, an increase in SupraVentricular (SVE) and Ventricular Extrasystoles (VE) was checked in comparison with the I group patients (p<0.05). Total SVE was significantly correlated with threonine (r=-0.316), serine (r=-0.336), glycine (r=-0.397), isoleucine (r=0.317), BCAA (r=0.356), and glycine+serine sum (r=-0.302), p<0.05. AF paroxysm was significantly correlated with taurine (r=-0.302), serine (r=-0.328), glycine (r=-0.311), glutamine (r=-0.304), and glycine+serine sum (r=-0.379), p<0.05. Total VE was significantly correlated with glycine (r=-0.370) and tyrosine (r=0.325), p<0.05. Changes in ST-segment were significantly correlated with tyrosine (r=0.307), phenylalanine (r=0.318), and Aromatic Amino Acids (AAA) (r=0.379), p<0.05. We concluded that glycine, serine, and BCAA are significantly correlated with cardiac arrhythmias. Changes in ST segment are significantly correlated with AAA levels. Keywords: heart rhythm violations, ischemia, arrhythmia, metabolomics.

Long-term disruption of tissue levels of glutamate and glutamatergic neurotransmission neuromodulators, taurine and kynurenic acid induced by amphetamine.

Chronic amphetamine (AMPH) use leading to addiction results in adaptive changes within the central nervous system that persist well beyond the drug's elimination from the body and can precipitate relapse. Notably, alterations in glutamatergic neurotransmission play a crucial role in drug-associated behaviours. This study aimed to identify changes induced by amphetamine in glutamate levels and the neuromodulators of glutamatergic neurotransmission (taurine and kynurenic acid) observable after 14 and 28 days of abstinence in key brain regions implicated in addiction: the cortex (Cx), nucleus accumbens (Acb), and dorsolateral striatum (CPu-L). The rats were administered 12 doses of amphetamine (AMPH) intraperitoneally (i.p.) at 1.5mg/kg. The behavioural response was evaluated through ultrasonic vocalizations (USV). High-performance liquid chromatography (HPLC) was used to measure the levels of glutamate, taurine, and kynurenic acid in the Cx, Acb, and CPu-L after 14 and 28 days of abstinence. AMPH administration led to sensitisation towards AMPH's rewarding effects, as evidenced by changes in USV. There was a noticeable decrease in kynurenic acid levels and an increase in both taurine and glutamate in the CPu-L, along with an increase in glutamate levels in the Cx, 28 days following the final AMPH injection. The most significant changes in the tissue levels of glutamate, taurine, and kynurenic acid were seen in the CPu-L 28 days after the last dose of AMPH. The emergence of these changes exclusively after 28 days suggests that the processes initiated by AMPH use and subsequent abstinence take time to become apparent and may be enduring. This could contribute to the incubation of craving and the risk of relapse. Developing pharmacological strategies to counteract the reduction in kynurenic acid induced by psychostimulants may provide new avenues for therapy development.

Longitudinal Biochemical and Behavioral Alterations in a Gyrencephalic Model of Blast-Related Mild Traumatic Brain Injury.

Blast-related traumatic brain injury (bTBI) is a major cause of neurological disorders in the U.S. military that can adversely impact some civilian populations as well and can lead to lifelong deficits and diminished quality of life. Among these types of injuries, the long-term sequelae are poorly understood because of variability in intensity and number of the blast exposure, as well as the range of subsequent symptoms that can overlap with those resulting from other traumatic events (e.g., post-traumatic stress disorder). Despite the valuable insights that rodent models have provided, there is a growing interest in using injury models using species with neuroanatomical features that more closely resemble the human brain. With this purpose, we established a gyrencephalic model of blast injury in ferrets, which underwent blast exposure applying conditions that closely mimic those associated with primary blast injuries to warfighters. In this study, we evaluated brain biochemical, microstructural, and behavioral profiles after blast exposure using in vivo longitudinal magnetic resonance imaging, histology, and behavioral assessments. In ferrets subjected to blast, the following alterations were found: 1) heightened impulsivity in decision making associated with pre-frontal cortex/amygdalar axis dysfunction; 2) transiently increased glutamate levels that are consistent with earlier findings during subacute stages post-TBI and may be involved in concomitant behavioral deficits; 3) abnormally high brain N-acetylaspartate levels that potentially reveal disrupted lipid synthesis and/or energy metabolism; and 4) dysfunction of pre-frontal cortex/auditory cortex signaling cascades that may reflect similar perturbations underlying secondary psychiatric disorders observed in warfighters after blast exposure.

IMPORTANCE OF EXCITOTOXICITY IN STRESS: A MINI REVIEW

Excitotoxicity refers to the process where nerve cells are damaged or killed due to excessive stimulation by neurotransmitters, primarily glutamate. This overactivation of receptors, such as NMDA (N-methyl-D-aspartate) receptors, causes an influx of calcium ions into the neurons, leading to cell damage or death. It is a key factor in various neurodegenerative diseases and acute neurological conditions like stroke and traumatic brain injury. Many researchers suggested that chronic stress can exacerbate excitotoxicity by increasing the release of glutamate in the brain. There are numerous factors play extremely important roles in many endorsing the excitotoxicity are increased glutamate levels, vulnerability of the neurones and neuro-degeneration in the diseases like Parkinsons. Several protective measures are obtained by the review of many researches. Effective stress management, including mindfulness, exercise, and therapy, can help regulate glutamate levels and reduce the risk of excitotoxicity.Enhancing antioxidant defences through diet or supplementation may protect neurons from the oxidative stress induced by excitotoxicity.Drugs that block NMDA receptors or regulate glutamate activity are being explored as treatments for conditions associated with excitotoxicity.

7 T characterization of excitatory and inhibitory systems of acute pain in healthy female participants.

Current understanding of the physiological underpinnings of normative pain processing is incomplete. Enhanced knowledge of these systems is necessary to advance our understanding of pain processes as well as to develop effective therapeutic interventions. Previous neuroimaging research suggests a network of interrelated brain regions that seem to be implicated in the processing and experience of pain. Among these, the dorsal anterior cingulate cortex (dACC) plays an important role in the affective aspects of pain signals. The current study leveraged functional MRS to investigate the underlying dynamic shifts in the neurometabolic signature of the human dACC at rest and during acute pain. Results provide support for increased glutamate levels following acute pain administration. Specifically, a 4.6% increase in glutamate was observed during moderate pressure pain compared with baseline. Exploratory analysis also revealed meaningful changes in dACC gamma aminobutyric acid in response to pain stimulation. These data contribute toward the characterization of neurometabolic shifts, which lend insight into the role of the dACC in the pain network. Further research in this area with larger sample sizes could contribute to the development of novel therapeutics or other advances in pain-related outcomes.

A 7T interleaved fMRS and fMRI study on visual contrast dependency in the human brain

Abstract Introduction: Functional magnetic resonance spectroscopy (fMRS) is a non-invasive technique for measuring dynamic changes in neurometabolites. While previous studies have observed concentration changes in metabolites during neural activation, the relationship between neurometabolite response and stimulus intensity and timing requires further investigation. To address this, we conducted an interleaved fMRS and functional magnetic resonance imaging (fMRI) experiment using a visual stimulus with varying contrast levels. Methods: A total of 20 datasets were acquired on a 7T MRI scanner. The visual task consisted of two STIM blocks (30 s/20 s ON/OFF, 4 min), with 10% or 100% contrast, interleaved with a 5 min REST block. A dynamic fitting approach was used for fMRS data analysis. For metabolite level changes, the STIM conditions were modeled in two different ways: either considering the full STIM block as active condition (full-block model) or only modeling the ON blocks as active condition (sub-block model). For linewidth changes due to the BOLD effect, STIM conditions were modeled using the sub-block model. Results: For both models, we observed significant increases in glutamate levels for both the 10% and 100% visual contrasts, but no significant difference between the contrasts. Decreases in aspartate, and glucose, and increases in total N-acetylaspartate and total creatine were also detected, although less consistently across both 10% and 100% visual contrasts. BOLD-driven linewidth decreases and fMRI-derived BOLD increases within the MRS voxel were observed at both 10% and 100% contrasts, with larger changes at 100% compared to 10% in the fMRI-derived BOLD only. We observed a non-linear relation between visual contrast, the BOLD response, and the glutamate response. Conclusion: Our study highlights the potential of fMRS as a complementary technique to BOLD fMRI for investigating the complex interplay between visual contrast, neural activity, and neurometabolism. Future studies should further explore the temporal response profiles of different neurometabolites and refine the statistical models used for fMRS analysis.

Neonatal Maternal Separation Induces Sexual Dimorphism in Brain Development: The Influence on Amino Acid Levels and Cognitive Disorders.

Repeated maternal separation (MS) is a useful experimental model in rodents for studying the long-term influence of early-life stress on brain neurophysiology. In our work, we assessed the effect of repeated MS (postnatal day (PND)1-21, 180 min/day) on the postnatal development of rat brain regions involved in memory using proton magnetic resonance spectroscopy (1HMRS) for tissue volume and the level of amino acids such as glutamate, aspartate, glutamine, glycine and gamma-aminobutyric acid (GABA) in the hippocampus. We assessed whether these effects are sex dependent. We also use novel object recognition (NOR) task to examine the effect of MS on memory and the effect of ethanol on it. Finally, we attempted to ameliorate postnatal stress-induced memory deficits by using VU-29, a positive allosteric modulator (PAM) of the metabotropic glutamate type 5 (mGlu5) receptor. In males, we noted deficits in the levels of glutamate, glycine and glutamine and increases in GABA in the hippocampus. In addition, the values of perirhinal cortex, prefrontal cortex and insular cortex and CA3 were decreased in these animals. MS females, in contrast, demonstrated significant increase in glutamate levels and decrease in GABA levels in the hippocampus. Here, the CA1 values alone were increased. VU-29 administration ameliorated these cognitive deficits. Thus, MS stress disturbs amino acids levels mainly in the hippocampus of adult male rats, and enhancement of glutamate neurotransmission reversed recognition memory deficits in these animals.

Ceftriaxone and selenium mitigate seizures and neuronal injury in pentylenetetrazole-kindled rats: Oxidative stress and inflammatory pathway

Epilepsy is one of the most serious worldwide neurological disorders that lead to the cognitive-psychosocial insults in recurrent seizures. About one third of the patients are drug-resistant, so innovative drugs are needed to manage seizures to improve the quality of life. Ceftriaxone is a cephalosporin antibiotic that increases the expression of glutamate transporters-1 and improves the neurobehavioral effects caused by increased glutamate level in the CNS. Selenium is well known antioxidant. The present study aimed to investigate ceftriaxone and selenium therapeutic effects against epilepsy in rats. Epilepsy was induced by PTZ given at a dose (50 mg/kg I.P) on alternative days for 13 days. Eighty rats were randomly divided into 8 groups: Group1-2; normal and vehicle control, Group 3; PTZ group, Group 4–8; kindled rats received selenium, ceftriaxone100, ceftriaxone200, selenium + ceftriaxone100 and selenium + ceftriaxone200 mg/kg/day respectively for a week. At the end of the study, behavioral tests were performed. Oxidative stress, inflammatory markers, neurotransmitters and GLT-1 were measured in brain tissue homogenate. Brain histopathological investigation was also done. PTZ-kindled rats exhibited increased Racine score, besides behavioral tests and histopathological changes, significant elevation in oxidative stress and inflammatory markers, with decrease in serotonin, dopamine, GABA levels and GLT-1 expressions. Selenium and Ceftriaxone alone or combined treatment decreased Racine score with remarkable improvement in behavioral and histopathological changes. The antioxidant enzymes, neurotransmitters and GLT-1 expressions were increased, along with reduced TNF-α, IL-1 levels. Current study showed that selenium + ceftriaxone100 group represents a possible approach to improve epilepsy particularly through inhibiting oxidative stress and inflammation.

Effects of memantine on mania-like phenotypes exhibited by Drosophila Shaker mutants.

Increased glutamate levels and electrolytic fluctuations have been observed in acutely manic patients. Despite some efficacy of the non-competitive NMDA receptor antagonist memantine (Mem), such as antidepressant-like and mood-stabilizer drugs in clinical studies, its specific mechanisms of action are still uncertain. The present study aims to better characterize the Drosophila melanogaster fly Shaker mutants (SH), as a translational model of manic episodes within bipolar disorder in humans, and to investigate the potential anti-manic properties of Mem. Our findings showed typical behavioral abnormalities in SH, which mirrored with the overexpression of NMDAR-NR1 protein subunit, matched well to glutamate up-regulation. Such molecular features were associated to a significant reduction of SH brain volume in comparison to Wild Type strain flies (WT). Here we report on the ability of Mem treatment to ameliorate behavioral aberrations of SH (similar to that of Lithium), and its ability to reduce NMDAR-NR1 over-expression. Our results show the involvement of the glutamatergic system in the SH, given the interaction between the Shaker channel and the NMDA receptor, suggesting this model as a promising tool for studying the neurobiology of bipolar disorders. Moreover, our results show Mem as a potential disease-modifying therapy, providing insight on new mechanisms of action.

Glutaminase 1 isoform up-regulation associated with lipid metabolism disorder induced by methyl tertiary-butyl ether in male rats

Methyl tertiary-butyl ether (MTBE) is a new unleaded gasoline additive, which is considered to be associated with abnormal lipid metabolism in many studies, but the metabolic characteristics and mechanism are still unclear. To observe the characteristics of lipid metabolism induced by MTBE and possible pathways, 21 male Wistar rats got intragastric administration for 24 weeks. The serum lipid metabolism indexes and metabolites were analyzed separately by a biochemical analyzer and untargeted metabolomics. And found that serum high-density lipoprotein cholesterol (HDL-C) levels in the exposure group were significantly reduced, and serum very low-density lipoprotein (VLDL) levels were significantly increased. In untargeted metabolomics, 190 differential metabolites were obtained. Among them, 23 metabolites were found to show the same trend in MTBE exposure groups, which might play a key role in systemic energy metabolism. Further metabolic pathways analysis showed that D-Glutamine, D-glutamate metabolism, and the other three pathways were affected by MTBE significantly. Therefore, we evaluated serum glutamine and glutamate levels and found that MTBE exposure significantly reduced glutamine levels and increased glutamate levels in rat serum and L-02 cells. Further, the key regulatory gene of glutamine metabolism, glutaminase 1 isoform (GLS1), was significantly up-regulated in rat liver and L-02 cells exposed to MTBE. While the effect of glutamine and glutamate metabolism induced by MTBE could be weakened by BPTES, an antagonist of GLS1. In conclusion, our results indicated that MTBE exposure could change the level of glutamine metabolism by promoting GLS1 expression and ultimately lead to abnormal lipid metabolism.

Modulatory effects of Nigella sativa l. oil on the hippocampus of dizocilpine-induced schizophrenia in BALB/c MICE

IntroductionSchizophrenia is a neuropsychiatric disorder characterised by positive, negative and cognitive behavioral symptoms. Despite years of research, the need for suitable therapy remains elusive. Nigella sativa oil (NSO) is a medicinal plant notable for its dietary, neuroprotective and anti-inflammatory properties. However, there is paucity of information on its neuroprotective potentials in schizophrenia.ObjectivesThis study was designed to investigate the modulatory effects of NSO on the hippocampus of dizocilpine-induced schizophrenia in mice.MethodsSixty 14-weeks old male BALB/c mice (23-25g) were divided into five groups (n=12); control (normal saline, 1 mL/kg), NSO (1 mL/kg), dizocilpine-control (0.5 mg/kg) all for 7 days, while NSO (1 mL/kg for 7 days) + dizocilpine (0.5 mg/kg, for another 7 days) for preventive measure, and dizocilpine (0.5 mg/kg for 7 days) + NSO (1 mL/kg for another 7 days) for reversal. Dizocilpine and NSO were administered intraperitoneally and orally, respectively. Open field box was used for stereotypic popping. Animals were euthanised after behavioral studies, and harvested brains were weighed. Hippocampal glutamate was determined spectrophotometrically. Neuronal arrangement, sizes and densities were determined in perfused brain tissues using haematoxylin and eosin stain. Dendritic arborisations were assessed using Golgi stain. Metabotropic glutamate receptor-II (mGluR-2) and Glia Fibrilliary Acidic Protein (GFAP) were evaluated immunohistochemically. Data were analysed using descriptive statistics and ANOVA at α0.05.ResultsStereotypic popping was observed in dizocilpine-control but not in the preventive and reversal NSO-treated animals. The NSO increased glutamate levels in the reversal (0.19±0.00 μM/μg tissue) but not in the preventive (0.18±0.00 μM/μg tissue) groups relative to dizocilpine-control (0.18±0.00 μM/μg tissue). Hippocampal neuronal density was significantly increased by dizocilpine (21.25±1.11neurons/100μm2) but modulated by NSO in the preventive (17.25±0.51 neurons/100μm2) and reversal groups (12.00±0.71 neurons/100μm2). Significant neuronal de-arborisation that occurred in the dizocilpine-control (989.90±253.9 μm2/2.5mm2area) was inhibited by NSO in the preventive (1678±370.90 μm2/2.5mm2area) and reversal (1639±314.80 μm2/2.5mm2area) treatments. Compared to dizocilpine-control (4219±127.3 ODU), NSO increased mGluR-2 expression in the preventive (4945±17.00 ODU) and reversal (4116±24.97 ODU) groups. The GFAP expression in NSO-treated animals relative to dizocilpine-control (5510±38.45 ODU) was significantly reduced in the preventive (4945±17.00 ODU) and reversal (4116±24.97 ODU) measures.ConclusionsNigella sativa oil mitigated schizophrenic symptoms induced by dizocilpine in mice via modulation of hippocampal glutamate, metabotropic glutamate receptor–II upregulation, astrogliosis inhibition and neuroprotective mechanisms.Disclosure of InterestNone Declared

Investigation of The Learning and Memory Enhancing Effects of 0.25 mA and 0.5 mA Anodal and Cathodal Transcranial Direct Current Stimulations in Healthy Rats

Objective: Our aim in this study was to investigate the effects of tDCS, which is known to be effective on AM-PA and NMDA, with different anodal and cathodal stimulation types and 0.25 mA and 0.5 mA current intensi-ties on learning and memory by behavioral and molecular mechanisms. Methods: 50 male Wistar rats weighing 290-310 g were divided into 5 groups as control, C1-tDCS, C2-tDCS, A1-tDCS and A2-tDCS. In the C1-tDCS group, 0.25 mA cathodal tDCS stimulation for 30 min per day for 5 days, in the C2-tDCS group for 30 min per day for 0.5 mA cathodal tDCS stimulation for 5 days, in the A1-tDCS group for 5 days with 0.25 mA anodal tDCS stimulation for 30 min per day and A2-tDCS group The tDCS group received 0.5 mA anodal tDCS stimulation for 30 minutes per day for 5 days. On the 6th and 7th days of the experiment, the locomotor activity, learning and memory behaviors of the rats were evaluated by open field test, y maze test and object localization test. In addition, glutamate levels were measured in hippocampus tis-sues by ELISA method. Results: It was observed that there were non-significant decreases in the results of the C1-tDCS and C2-tDCS groups in which cathodal stimulation was applied compared to the control group in locomotor activity, learning and memory data. On the other hand, an increase was observed in the data of the A1-tDCS and A2-tDCS groups in which anodal stimulation was applied, and the increase in the data of the A2-tDCS group from these groups was found to be statistically significant compared to the control (p<0.05). Similar results were also seen in glu-tamate levels. A non-significant decrease in glutamate levels was observed in the C1-tDCS and C2-tDCS groups compared to the control, while an insignificant increase in glutamate levels in the A1-tDCS group was observed. On the other hand, there was a significant increase in glutamate level in the A1-tDCS group compared to the control group (p<0.05). Conclusion: In conclusion, our data showed that 0.5 mA anodal tDCS stimulation for 30 min for 5 days can enhance learning and memory on the glutamatergic pathway.

Activation of calcium-sensing receptors in the basolateral nucleus of the amygdala inhibits food intake and induces anxiety-depressive-like emotions via dopamine system

The calcium-sensing receptor (CaSR) is abundantly expressed in gastrointestinal mucosa and participates in the regulation of feeding by affecting hormone secretion. Studies have demonstrated that the CaSR is also expressed in feeding-related brain areas, such as the hypothalamus and limbic system, but the effect of the central CaSR on feeding has not been reported. Therefore, the aim of this study was to explore the effect of the CaSR in the basolateral amygdala (BLA) on feeding, and the potential mechanism was also studied. CaSR agonist R568 was microinjected into the BLA of male Kunming mice to investigate the effects of the CaSR on food intake and anxiety-depression-like behaviours. The enzyme-linked immunosorbent assay (ELISA) and fluorescence immunohistochemistry were used to explore the underlying mechanism. Our results showed that microinjection of R568 into the BLA could inhibit both standard and palatable food intake in mice for 0–2 h, induce anxiety-depression-like behaviours, increase glutamate levels in the BLA, and activate dynorphin and gamma-aminobutyric acid neurons through the N-methyl-D-aspartate receptor and thus reduce the content of dopamine in the arcuate nucleus of the hypothalamus (ARC) and ventral tegmental area (VTA), respectively. Our findings suggest that activation of the CaSR in the BLA inhibited food intake and caused anxiety-depression-like emotions. The reduced dopamine levels in the VTA and ARC via glutamatergic signals are involved in these functions of CaSR.

Neuro-protective potentials of N-acetylcysteine and zinc against di(2-ethylhexyl)-phthalate-induced neuro-histopathology and dys-regulations of Dopamine and Glutamate in rat brain

This study examined neuro-protective potentials of N-acetyl-cysteine (NAC) and Zinc on expression levels of Dopamine and Glutamate in the Cerebrum, Hypothalami and Pituitary Glands in Di(2-ethylhexyl)-phthalate (DEHP)-induced neurotoxicity in rats. Thirty-six adult male Wistar rats were randomly divided into 6 groups (n = 6). Group 1 was control. Groups 2-6 received oral administrations of 100 mg/kg NAC, 0.5 mg/kg Zinc, 750 mg/kg DEHP, DEHP + NAC doses and DEHP + Zinc doses respectively for 21 days. Brain histology (Heamatoxyline and Eosine technique), histochemical and enzyme-linked-immunosorbent assays of Dopamine and Glutamate in homogenates of Cerebrum, Hypothalami and Pituitary Glands were evaluated. Data were statistically analyzed using One-way-ANOVA with Tukey-post-hoc test at p ≤ 0.05. Histo-pathological evaluations of Cerebrum, Hypothalami and Pituitary Glands showed gross histo-alterations and neurodegenerative changes (Group 4), mild histo- and neuro-degenerative changes (Groups 5 and 6) and normal histology (Group 1). Histochemical analyses showed higher Dopamine levels in Hypothalami (Group 5) and Pituitary Glands (Groups 5 and 6), compared with Group 4. Furthermore, results showed lower Glutamate levels in Cerebrum, Hypothalami and Pituitary Glands of Groups 5 and 6, compared with Group 4. Overall, NAC and Zinc conferred neuro-protection and histo-protection against DEHP-induced neuro-toxicity, neuro-histopathology, decreased Dopamine levels and increased Glutamate levels.

Ozone reduces ischemic damage after a stroke by regulating the autophagy of astrocytes.

Stroke is a common and damaging disease of brain tissue, and has high morbidity, disability, and mortality rates. Ozone (O3) is an isomer of oxygen and can be applied to ozonate the isolated blood in specific containers outside the body and return it to the body. O3 can also alter the activity and function of multiple cellular components, thus affecting blood viscosity and altering hemodynamics. However, the question of whether O3 has clinical value in the treatment of stroke requires further investigation. This study sought to evaluate the protective effect and possible mechanism of O3 in brain injury after stroke. First, oxygen-glucose deprivation/reoxygenation (OGD/R)-induced human glioblastoma cell (A172) and middle cerebral artery occlusion (MCAO) rat models were established. Second, the levels of the associated ribonucleic acids and proteins were analyzed using reverse-transcription real-time-quantitative polymerase chain reaction, Western Blot, or immunofluorescence assays. Third, the concentration of glutamate and lactate dehydrogenase (LDH) were assessed using enzyme-linked immunoassays. The results showed that glial fibrillary acidic protein was upregulated in the OGD/R A172 cells. O3 decreased LDH and increased glutamate levels in the OGD/R A172 cells, which suggests that O3 reduced brain damage in the in vitro stroke model. We also showed that O3 attenuated brain infarction in the in-vivo stroke model. Further, we found that O3 alleviated stroke-induced brain damage by reducing the apoptosis of astrocytes. Further, the B-cell lymphoma 2 inhibitor propofol alleviated stroke-induced brain damage. Thus, O3 notably alleviated stroke-induced brain damage by inhibiting the apoptosis of astrocytes in the OGD/R-induced human glioblastoma cell and MACO rat models.