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Premna odorata Blanco (Lamiaceae) is an ethnomedicinal plant, where some reports claimed their anti-inflammatory, cytotoxic, and antituberculosis effects, without investigating its role on the brain. Therefore, forty mature male rats were equally divided into 4 groups; the 1st was kept as control. Rats in groups 2 and 4 were orally given P. odorata extract daily at a dose of 500 mg/kg B.W., while those in groups 3 and 4 were daily administrated aluminum chloride "AlCl3" (70 mg/kg B.W.). The treatments extended for 30 successive days. At the end of the experimental period, brain samples were collected for biochemical assay of glutathione reductase (GSH), catalase, malondialdehyde (MDA), and acetylcholinesterase activity (AChE). Besides, monoamines (norepinephrine, dopamine, serotonin), amino acids (glutamine, serine, arginine, taurine and gamma-aminobutyric acid (GABA)), neurotransmitters, DNA damage, cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF)-α genes were estimated. Moreover, brain samples were obtained for histopathological investigation. Aluminum toxicity resulted in a decline of GSH concentration, elevation of MDA, and AChE activity. Except for GABA which exhibited a significant decrease, there was a marked increase in the measured amino acid and monoamine neurotransmitters. Also, an increase in mRNA expressions of TNF-α and COX-2 was detected. It was noticed that Premna odorata extract reduced the oxidative stress and counteracted the augmentations in AChE caused by AlCl3. Marked improvements in most measured neurotransmitters with downregulation of pro-inflammatory gene expression were recorded in P. odorata + AlCl3 group. Premna odorata restores the altered histopathological feature induced by AlCl3. In conclusion, the present findings clarify that P. odorata extract could be important in improving and treatment of neurodegenerative disorders as it was able to reduce oxidative stress, DNA damage, biochemical alterations, and histopathological changes in rats exposed to AlCl3 toxicity. [ABSTRACT FROM AUTHOR]

• Lead intoxication decreased serum TSH level in school- age children. • Lead intoxication increased serum GABA level in school- age girls. • BLL and serum Glu level were negatively correlated with school- aged children's IQ. • The frequency of mother smoking and drinking un-boiled stagnant tap water were risk factors of lead intoxication. • Eating fresh fruits, vegetables and soy products regularly may protect against lead intoxication. Lead exposure is one of the most concerning public health problems worldwide, particularly among children. Yet the impact of chronic lead exposure on the thyroid status and related intelligence quotient performance among school-age children remained elusive. The aim of this study was to evaluate the influence of lead exposure on the thyroid hormones, amino acid neurotransmitters balances, and intelligence quotient (IQ) among school-age children living nearby a lead-zinc mining site. Other factors such as rice lead levels, mothers' smoking behavior, and diet intake were also investigated. A total of 255 children aged 7-12 years old were recruited in this study. Blood lead level (BLL), thyroid hormones including free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH), and amino acid neurotransmitters such as glutamate (Glu), glutamine (Gln), and γ-aminobutyric acid (GABA) were measured using graphite furnace atomic absorption spectroscopy (GFAAS), chemiluminescence immunoassay, high performance liquid chromatography (HPLC). Raven's standard progressive matrices (SPM) and the questionnaire were used to determine IQ and collect related influence factors. The average BLL of children was 84.8 μg/L. The occurrence of lead intoxication (defined as the BLL ≥ 100 μg/L) was 31.8%. Serum TSH levels and IQ of lead-intoxicated children were significantly lower than those without lead toxicity. The GABA level of girls with the lead intoxication was higher than those with no lead-exposed group. Correlation analyses revealed that BLL were inversely associated with the serum TSH levels (R= -0.186, p < 0.05), but positively related with IQ grades (R = 0.147, p < 0.05). Moreover, BLL and Glu were inversely correlated with IQ. In addition, this study revealed four factors that may contribute to the incidence of lead intoxication among children, including the frequency of mother smoking (OR = 3.587, p < 0.05) and drinking un-boiled stagnant tap water (OR = 3.716, p < 0.05); eating fresh fruits and vegetables (OR = 0.323, p < 0.05) and soy products regularly (OR = 0.181, p < 0.05) may protect against lead intoxication. Lead exposure affects the serum TSH, GABA levels and IQ of school-aged children. Developing good living habits, improving environment, increasing the intake of high-quality protein and fresh vegetable and fruit may improve the condition of lead intoxication. [ABSTRACT FROM AUTHOR]

The article focuses on a study which identified bacteriophages, bacterial species and fecal metabolites showing notable differences in abundance between major depressive disorder patients and healthy individuals. Gut bacteria and bacteriophage differences between MDD and HC subjects are described. Direct roles of the gut microbiome in modulating fecal amino acid metabolism by mapping the differential enzyme commission numbers to disturbed amino acid metabolism is explored.

Purpose: In 2004, Boumezbeur et al proposed a simple yet powerful approach to detect the metabolism of 13C‐enriched substrates in the brain. Their approach consisted of dynamic 1H‐MRS, without a 13C radiofrequency (RF) channel, and its successful application was demonstrated in monkeys. Since then, this promising method has yet to be applied rigorously in humans. In this study, we revisit the use of dynamic 1H‐MRS to measure the metabolism of 13C‐enriched substrates and demonstrate its application in the human brain. Methods: In healthy participants, 1H‐MRS data were acquired dynamically before and following a bolus infusion of [1‐13C] glucose. Data were acquired on a 3T clinical MRI scanner using a short‐TE SPECIAL sequence, with regions of interest in both anterior and posterior cingulate cortex. Using simulated basis spectra to model signal changes in both 12C‐bonded and 13C‐coupled resonances, the acquired spectra were fit in LCModel to obtain labeling time courses for glutmate and glutamine at both C4 and C3 positions. Results: Presence of the 13C label was clearly detectable, owing to the pronounced effect of heteronuclear (13C‐1H) scalar coupling on the observed 1H spectra. A decrease in signal from 12C‐bonded protons and an increase in signal from 13C‐coupled protons were observed. The fractional enrichment of Glu‐C4, (Glu+Gln)‐C4, and (Glu+Gln)‐C3 at 30 minutes following infusion of [1‐13C] glucose was similar in both regions: 11% to 13%, 9% to 12% and 3% to 5%, respectively. Conclusion: These preliminary results confirm the feasibility of the use of dynamic 1H‐MRS to monitor 13C labeling in the human brain, without a 13C RF channel. [ABSTRACT FROM AUTHOR]

Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1-/- mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy. [ABSTRACT FROM AUTHOR]

Amino acid neurotransmitters have been shown to correlate with Tourette syndrome (TS) and its comorbidities. In this study, we investigated the effects of Jian-Pi-Zhi-Dong Decoction (JPZDD), a formula containing 10 different Chinese medical herbs, on amino acid neurotransmitters in rats. We established a rat model of Tourette syndrome and comorbid anxiety with an iminodipropionitrile injection plus uncertain empty water bottle stimulation for 3 weeks. Then the rats were randomly divided into four groups: control group and model group were gavaged with saline, while the remaining two treatment groups were gavaged with fluoxetine hydrochloride or JPZDD for four consecutive weeks. We recorded the behaviors of the rats with TS and comorbid anxiety by stereotypy recording, open field test, and elevated plus maze. We observed mitochondrial changes with transmission electron microscopy. We measured the content of glutamate (GLU) and γ-aminobutyric acid (GABA) both in the serum and striatum and the expression of their receptors by Western blot and real-time polymerase chain reaction. The study revealed that JPZDD was effective in alleviating the behavioral symptoms of both tic and anxiety in the rat model groups. These results might be associated with the increase in GABA levels and decrease in GLU levels in the serum, as well as an increase in striatal GABA level by the activation of GABA receptors Type A (GABAAR). JPZDD treatment also reversed the mitochondrial dysfunction both in the striatum and cortex in affected animals. [ABSTRACT FROM AUTHOR]

Function of brain amino acids as neurotransmitters or their precursors implies changes in the amino acid levels and/or metabolism in response to physiological and environmental challenges. Modelling such challenges by pregnancy and/or hypoxia, we characterize the amino acid pool in the rat cerebellum, quantifying the levels and correlations of 15 amino acids and activity of 2-oxoglutarate dehydrogenase complex (OGDHC). The parameters are systemic indicators of metabolism because OGDHC limits the flux through mitochondrial TCA cycle, where amino acids are degraded and their precursors synthesized. Compared to non-pregnant state, pregnancy increases the cerebellar content of glutamate and tryptophan, decreasing interdependence between the quantified components of amino acid metabolism. In response to hypoxia, the dependence of cerebellar amino acid pool on OGDHC and the average levels of arginine, glutamate, lysine, methionine, serine, phenylalanine, and tryptophan increase in non-pregnant rats only. This is accompanied by a higher hypoxic resistance of the non-pregnant vs. pregnant rats, pointing to adaptive significance of the hypoxia-induced changes in the cerebellar amino acid metabolism. These adaptive mechanisms are not effective in the pregnancy-changed metabolic network. Thus, the cerebellar amino acid levels and OGDHC activity provide sensitive markers of the physiology-dependent organization of metabolic network and its stress adaptations. [ABSTRACT FROM AUTHOR]

Polycrystalline samples of (La1-xAx)0.67Ba0.33Mn1.05O3-δ, with A being a mixture of lanthanides containing 66% La, 22% Nd, 8% Pr, and 4% Ce, were prepared by the glycine-nitrate method, with target compositions of x=0, 0.33, 0.67, and 1. The effect of the mixture of lanthanides on the Curie temperature, TC, and the magnetocaloric properties was investigated. The prepared samples are single phase, with space group R3c. The lattice parameters and average A-site ionic radius, rA decrease linearly with x while the size disorder, as characterized by the variance, σ2, increases from 0.014 to 0.017 with x. As x is increased, the increase in σ2 drives a linear decrease in TC. The magnetic entropy change, ΔSM, for a field change of 1 T is obtained by magnetization measurements, giving a maximum value of 1.7 J/kg K, and a relative cooling power of 43 J/kg, independent of x. These results suggest that replacing lanthanum with a mixture of lanthanides is a realistic way to tune the working temperature of magnetocaloric manganites while maintaining a constant magnetocaloric effect. [ABSTRACT FROM AUTHOR]

Polycrystalline samples of (La1-xAx)0.67Ba0.33Mn1.05O3-δ, with A being a mixture of lanthanides containing 66% La, 22% Nd, 8% Pr, and 4% Ce, were prepared by the glycine-nitrate method, with target compositions of x=0, 0.33, 0.67, and 1. The effect of the mixture of lanthanides on the Curie temperature, TC, and the magnetocaloric properties was investigated. The prepared samples are single phase, with space group R3c. The lattice parameters and average A-site ionic radius, rA decrease linearly with x while the size disorder, as characterized by the variance, σ2, increases from 0.014 to 0.017 with x. As x is increased, the increase in σ2 drives a linear decrease in TC. The magnetic entropy change, ΔSM, for a field change of 1 T is obtained by magnetization measurements, giving a maximum value of 1.7 J/kg K, and a relative cooling power of 43 J/kg, independent of x. These results suggest that replacing lanthanum with a mixture of lanthanides is a realistic way to tune the working temperature of magnetocaloric manganites while maintaining a constant magnetocaloric effect. [ABSTRACT FROM AUTHOR]

• An LC-MS/MS method for determination of Gly, GABA, Asp, Tau, and Glu was developed. • This LC-MS/MS method was validated and applied to patients with schizophrenia. • The reference intervals were established in Chinese adult population. • Plasma Tau, Asp, and Glu levels are altered in patients with schizophrenia. Schizophrenia is a serious mental disease with unknown etiology that affects approximately 1 % of the population around the world. Altered levels of amino acid neurotransmitters may underlie the physiopathology of schizophrenia (SZ). This study aimed to develop a rapid and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of glutamate acid (Glu), aspartic acid (Asp), γ-aminobutyric acid (GABA), glycine acid (Gly), and Taurine acid (Tau) in patients with schizophrenia plasma and establish reference intervals for Chinese adult populations, and applied to patients with schizophrenia for a preliminary exploration of changes in their plasma levels of five amino acid neurotransmitters. Sample treatment involved protein precipitation followed by dansyl chloride (DNS-Cl) derivatization and total run time is 5.8 min. The method was validated according to the latest national and international guidelines, which achieved acceptable precision (0.54–14.54 %) and accuracy (97.06–103.82 %). The reference interval for Glu, Asp, Gly, Tau, and GABA were 55.51–189.06, 27.51–92.38, 204.01–574.55, 107.50–227.65, and <1 μmol/L, respectively. Increased Tau levels and decreased Asp and Glu levels were shown in patients with schizophrenia. This method was suitable for clinical routine detection of plasma 5 amino acid neurotransmitters in Chinese adult populations. [ABSTRACT FROM AUTHOR]

Various aspects of the ab initio-based parametrization of an exciton model of amide I vibrations in peptides are discussed. Adopting “glycine dipeptide” (Ac-Gly-NHCH3) as a simple building-block model that describes the vibrational interaction between two peptide units, we perform comprehensive quantum-chemical calculations to investigate the effect and importance of the level of theory, the choice of local coordinates, and the localization method. A solvent continuum model description turns out important to obtain planar CONH peptide units when a full geometry optimization (which is necessary to obtain the correct frequencies) is performed. To study the conformational dependence of the amide I vibrations, we calculate ([lowercase_phi_synonym],ψ) maps of the local-mode frequencies and couplings. Performing conformational averages of the ([lowercase_phi_synonym],ψ) maps with respect to the most important peptide conformational states in solution (α, β, PII, and C5), we discuss the relation between these measurable quantities and the corresponding conformation of the peptide. Finally, the transferability of these maps to dipeptides with hydrophilic and hydrophobic side chains as well as to tripeptides with charged end groups is investigated. [ABSTRACT FROM AUTHOR]

The structural parameters, relative stability, proton transfer energy barriers of four typical and life related isomers and conformers of different charged (n=0,±1,±2) glycine species have been investigated using B3LYP, BHLYP, and CCSD(T) methods. Results indicate that those neutral and (±1)-charged species are stable. For the (+2)-charged cases, all four triplet-state glycine species and only the singlet-state zwitterionic one are stable. On the other hand, only the singlet-state zwtterionic glycine (1GlyZW(-2)) and the corresponding neutral form counterpart (1Gly(-2)) are stable for the (-2)-charged cases. Either of the two stable structures holds a proton lying in the position (2–3 Å) of being separated from its corresponding parental species. Those unstable divalent glycine species are dissociated into different smaller species spontaneously according to the characters of their different structures and electron spins. The presented fragmentation and deformation mechanisms can effectively predict and satisfactorily explain some experimental phenomena, which had been puzzling the mass spectrometry chemists. Also, the mechanisms should be suitable for any other similar molecule systems. Comparisons of the relative energies of the four (+1)-charged glycine species show that doublet-state glycine III (2GlyIII1) is more stable in energy by 12.1 kcal/mol than the (+1)-charged glycine Gly (2Gly1). This is consistent with the energy ordering of their corresponding mono-valence metal ion-bound derivatives. In addition, calculations show that an intramolecular proton transfer of 2Gly(-1) to become its zwitterionic counterpart is preferred due to its least activation energy barrier (5.8 kcal/mol) among four discussed processes. ©2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

We report the gas-phase preparation of negatively charged glycine as well as the Gly·(H2O)1,2- complexes by entrainment of the neutral precursor into an ionized supersonic expansion tuned to optimize the (H2O)n-·Arm clusters. The photoelectron spectrum of Gly- displays the signature of a dipole-bound species, with sufficient vibrational fine structure to characterize the core neutral as a higher energy, non-zwitterionic isomer of the amino acid. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Various configurations were investigated to find the most stable structures of glycine–(water)[sub 3] complex. Five different optimized conformers of glycine–(water)[sub 3] complex are obtained from density functional theory calculations using 6-311++G[sup *] basis set. Relaxation energy and many body interaction energies (two, three, and four body) are also calculated for these conformers. Out of the five conformers, the most stable conformer has the BSSE corrected total energy -513.917 967 7 Hartree and binding energy -27.28 Kcal/mol. It has been found that the relaxation energies, two body energies and three body energies have significant contribution to the total binding energy whereas four body energies are very small. The chemical hardness and chemical potential also confirmed the stability of the conformer having lowest total energy. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Rationale: Ethanol-induced behavioural sensitization (EBS) does not occur uniformly in mice exposed to the sensitization paradigm. This suggests innate differential responses to ethanol (EtOH) in the reward circuitry of individual animals. Objectives: To better characterize the adaptive differences between low-sensitized (LS) and high-sensitized (HS) mice, we examined excitatory amino acid (EAA) and inhibitory amino acid (IAA) neurotransmitter levels in the nucleus accumbens (NAc) during EBS expression. Methods: Male DBA/2J mice received five ethanol (EtOH) (2.2 g/kg) or saline injections, and locomotor activity (LMA) was assessed during EBS induction. EtOH mice were classified as LS or HS on the basis of final LMA scores. Following an EtOH challenge (1.8 g/kg) 2 weeks later, LMA was re-evaluated and in vivo microdialysis samples were collected from the NAc. Results: Most differences in amino acid levels were observed within the first 20 min after EtOH challenge. LS mice exhibited similar glutamate levels compared with acutely treated (previously EtOH naïve) mice, and generally increased levels of the IAAs GABA, glycine, and taurine. By contrast, HS mice exhibited increased glutamate and attenuated levels of GABA, glycine, and taurine. Conclusion: These data suggest that the profile of amino acid neurotransmitters in the NAc of LS and HS mice significantly differs. Elucidating these adaptive differences contributes to our understanding of factors that confer susceptibility/resilience to alcohol use disorder. [ABSTRACT FROM AUTHOR]

A novel nano‐sized MRI probe sensitive to zwitterionic amino acid neurotransmitters (ZNTs) was prepared by the conjugation of bismacrocyclic ZNT‐responsive units to a generation 4 (G4) polyamidoamine (PAMAM) dendrimer. In vitro evaluation through 1H NMR relaxometric titrations provided binding profiles revealing a surface morphology‐dependent interaction with the ZNTs. The positively charged dendrimeric periphery gave higher initial relaxivities and a milder decrease upon interaction with the target molecules. To improve solubility under physiologically relevant conditions, polyethylene glycol (PEG) units were additionally conjugated to the dendrimeric surface. The PEGylated conjugate displayed discrimination towards acetylcholine and a slightly increased binding affinity towards glutamate over the massively abundant competitive metabolite hydrogencarbonate. [ABSTRACT FROM AUTHOR]

We report a novel ditopic Gd(III)-based probe selective to zwitterionic amino acid neurotransmitters (ZNTs) crafted for ratiometric MRI imaging. The probe displayed increased binding affinity to ZNTs and non-synchronized concentration-dependent changes of the r1- and r2-relaxivity. Through the application of a T2/T1 weighted MRI strategy, we demonstrated signal enhancement for cooperatively bound glutamate and γ-aminobutyric acid ZNTs over competitive hydrogencarbonate, which remained MR silent. [ABSTRACT FROM AUTHOR]

Introduction. Systemic administration of pentylenetetrazole (PTZ) causes brain damage (BD), and triggers a series of morphological and neurochemical changes, which in turn bring about behavioral, cognitive, and motor deficits. Serotonin (5-HT), dopamine (DA), and noradrenaline (NA) levels are controlled by various brain structures and these levels are related to motor activity; however, the concentration of these neurotransmitters during the postictal process remains unknown. Objective. We investigated the concentration of 5-HT, NA and DA in the hippocampus, cerebellum, and cortex on motor deficit during the postictal stage. Method. Eighteen male Wistar rats (300 g) assigned to two groups: control (n = 9, saline solution) and experimental (n = 9, PTZ) were used. Myoclonic shakes were counted and motor behavior assessments were recorded during three hours post PTZ injection (90 mg/kg). The cortex, cerebellum, and hippocampus of each rat were dissected to determine the 5-HT, DA, and NA concentration by high performance liquid chromatography. Results. PTZ induced a significant increase in total 5-HT and DA levels in the hippocampus and cortex; in the cerebellum there was a significant increase in the concentration of 5-HT and NA. The presence of myoclonic shakes as well as a marked motor deficit in the experimental group were significantly different in comparison to the control. Discussion and conclusion. 5-HT modifies the concentration of other monoamines directly involved in motor aspects such as NA and DA in the hippocampus, cerebellum, and cortex during the postictal process. [ABSTRACT FROM AUTHOR]

Background: Acupuncture stimulation at GV26 during the acute phase of cerebral ischaemia can effectively reduce brain damage induced by ischaemic injury. However, the time course of the effects of acupuncture stimulation has not yet been thoroughly studied. Objective: To investigate the effects of manual acupuncture (MA) on glutamic acid (Glu) and γ-aminobutyric acid (GABA) expression in the cerebrospinal fluid of rats with middle cerebral artery occlusion (MCAO) and determine whether there is a temporal effect of acupuncture on the treatment of cerebral ischaemia. Methods: We performed thread occlusion of the right middle cerebral artery in rats to establish an animal model of MCAO. Simultaneously, during acupuncture treatment, microdialysis was used to continuously and dynamically observe immediate alterations in amino acid metabolism with acupuncture stimulation after cerebral ischaemia in vivo in this rat model of MCAO. Results: We found that, in comparison with an untreated MCAO group, Glu content was significantly decreased during the first acupuncture stimulation and during the course of the acupuncture treatment in the MCAO+MA group (MCAO vs MCAO+MA: day 1, P=0.032; day 2, P=0.021; day 3, P=0.017). These findings were also seen after the end of treatment when acupuncture was no longer applied (MCAO vs MCAO+MA: day 7, P=0.009). Measurements of GABA content following cerebral ischaemic injury showed that GABA peaks 24 hours after damage, falls thereafter and decreases to baseline levels on day 7. In the MCAO+MA group, GABA content on days 1 to day 2 was lower than in the MCAO group (MCAO+MA vs MCAO: day 1, P=0.003; day 2, P=0.001), although it was higher than in the control group (MCAO+MA vs control: day 1, P=0.024; day 2, P=0.009). GABA content on day 3 and day 7 was higher in the MCAO+MA group than in the MCAO group and the control group (MCAO+MA vs MCAO: day 3, P=0.008; day 7, P=0.013; MCAO+MA vs control: day 3, P=0.002; day 7, P=0.009). Conclusion: Acupuncture stimulation at GV26 can effectively decrease excessive release of Glu induced by ischaemia and maintain the endogenous inhibitory activity of GABA. This phenomenon was seen during the entire course of acupuncture treatment and continued for some time after the end of acupuncture treatment. [ABSTRACT FROM AUTHOR]

Introduction. Propoxazepam (3-alcoxyderivative of 1.4-benzodiazepine), in the tail-flick test and picrotoxin-induced convulsions showed significant analgesic and antiepileptic activity. Flumazenil (GABA antagonist) reduced its analgesic action, although antiseizure activity was changed slightly. As specific propoxazepam actions are anticonvulsant (1 subtype GABAA-R) and analgesic (2 subtype GABAA-R in the spinal cord), it can be suggested that the substance has no abuse-related side-effects. Materials and method. The possible involvement of the GABA system in the antinociceptive effect of propoxazepam was examined by administering flumazenil (1 and 10 mg/kg, i.p.), a selective GABA- receptor antagonist, 30 min prior to propoxazepam (1.8 and 10 mg/kg, orally) in rats. Picrotoxin solution (6.5 mg/kg, 95 % of lethality effect in mice) was injected subcutaneously 30 min after propoxazepam administration. Flumazenil was administered intraperitoneally 0.5 hour prior to propoxazepam administration. Time counting was starting from the convulsant injection and during the supervision time, the number of myoclonic convulsions and tonic extensia, time of their onset, as well as time to lethal effect (survival time), were registered. Results. Flumazenil and propoxazepam antiseizure effect in the picrotoxin-induced seizures test were estimated as 5.24±2.38 and 0.37±0.07 mg/kg. Antiseizure effect of propoxazepam was reduced with flumazenil administration. Flumazenil (1 mg/ kg) had no effect in tail-flick test but abolished the antinociceptive action of propoxazepam (tail flick latency period changes were -1.6% and +55.1, compared to control and propoxazepam alone administration, respectively). Conclusions. The mechanism of propoxazepam antiseizure and antinociceptive actions are GABA-R determined. Analgesic action mechanism assumes additional biotargets involvement. [ABSTRACT FROM AUTHOR]

Highlights • Chemically or electrically induced status epilepticus (SE) to induce epilepsy. • Hippocampal levels of acetylcholine and amino acids determined by microdialysis. • Acetylcholine increases during SE in both models but model-dependent changes in GABA and glutamate. • Few consistent changes in both models during latent period or chronic epileptic state. • Neurotransmitter changes differ markedly between post-SE models of epilepsy. Abstract Chemically or electrically induced status epilepticus (SE) in rodents is a commonly used method for induction of epilepsy. Structural and functional changes in the hippocampus play a pivotal role in epileptogenesis induced by SE. Although cholinergic mechanisms have long been thought to play an important role in the onset and propagation of epileptic seizures, not much is known about the potential role of acetylcholine (ACh) in ictogenesis and epileptogenesis in SE models of temporal lobe epilepsy. Here we used in vivo microdialysis to determine extracellular levels of ACh and, for comparison, several amino acid transmitters in the ventral hippocampus during SE, epileptogenesis, and the chronic epileptic state in two rat models of SE-induced epilepsy. SE was either induced by lithium-pilocarpine or by sustained electrical stimulation of the basolateral amygdala (BLA). ACh increased during SE in both models. Pretreatment with the muscarinic receptor antagonist scopolamine before BLA stimulation reduced SE severity and duration. In contrast to ACh, no consistent changes in amino acid levels were found during SE in the two models. During epileptogenesis and the chronic epileptic state, the only commonalities found in both models were a decrease in ACh in epileptic rats during the chronic epileptic state and a decrease in aspartate during epileptogenesis. The data demonstrate complex, model-dependent alterations in extracellular levels of ACh and amino acid neurotransmitters and only few commonalities. Thus, data originating from only one model of post-SE epilepsy should not be generalized but may have a limited translational value for understanding ictogenesis or epileptogenesis. [ABSTRACT FROM AUTHOR]

Objectives: This study is designed to evaluate the role of tuberoinfundibular peptide of 39 (TIP39) in connection with glucocorticoid receptor‐mediated glutamate/GABA abnormalities in chronic unpredictable mild stress (CUMS) model. Methods: Male Sprague–Dawley rats were treated with TIP39 (1 and 10 nmol, i.c.v) and diazepam 2 mg/kg throughout the stress period (28 days) in alternate days. Then, rats were subjected for different behavioural activity followed by biochemical, gene expression and histological examinations. Key findings: Chronic unpredictable mild stress rats showed significant cognitive impairment in Morris water maze, Novel object recognition and Y maze test. This was reversed after TIP39 administration. Moreover, TIP39 significantly decreased the brain glutamate and acetyl cholinesterase levels in CUMS rats, whereas it increases the level of GABA after TIP39 treatment. These changes were evident with increased glutamic acid decarboxylase enzyme activity by TIP39. TIP39 significantly decreased the brain glucocorticoid and mineralocorticoid receptor expression ratio in comparison with CUMS rats. Moreover, histological abnormalities in prefrontal cortex and hippocampus were markedly improved after TIP39 administration in CUMS rats. Conclusions: Tuberoinfundibular peptide of 39 can be a potent neuroendocrine modulator in treating cognitive impairment induced by CUMS rats by controlling glucocorticoid receptor‐mediated glutamate/GABA abnormalities in brain. [ABSTRACT FROM AUTHOR]

Samarium chloride coordinated with salicylic acid (SMS) and samarium chloride coordinated with two organic ligands glycine and salicylic acid (SMGS) have been grown by low temperature solution technique i.e., slow evaporation method. The crystalline nature of the material was firstly confirmed by single crystal X-ray diffraction analysis and secondly by powder X-ray diffraction analysis. It has been observed that the material prepared crystallizes in monoclinic system having space group P121/c1. The modes of vibration of different molecular group present in SMS and SMGS have been confirmed by Fourier transform infrared (FTIR) analysis. It indicates the coordination of ligands in complexes i.e., salicylic acid coordinated through oxygen atoms of carbonyl group (C=O) and glycine ligand coordinated through nitrogen atoms. UV-Vis transmittance study analyzes the optical transparency of SMS and SMGS and it has been found that with the incorporation of glycine in SMS transmittance decreases. Moreover, the impact of glycine in SMS single crystal on its various optical parameters such as optical band gap, refractive index and optical conductivity has been calculated. The decrease in the value of optical band gap from 3.43 to 3.29 eV with the incorporation of glycine in SMS has been observed. The calculated values of refractive index at 425 nm for SMS and SMGS complexes are 1.30 and 2.46 respectively and the optimum value of optical conductivity at 425 nm for SMS and SMGS is 4 105 and 1.4 107 Sm−1 respectively. Luminescence of Sm3+ ion is strongly sensitized by salicylic acid as compared to glycine thereby fluorescence of the SMGS complex diminished. Decrease in the dielectric constant was observed with the incorporation of glycine in SMS single crystal. Complex electric modulus analysis confirms the non-Debye type of relaxation in both the materials. Activation energy value depends on frequency as well as on glycine coordination in SMS single crystal. [ABSTRACT FROM AUTHOR]

Sensory perception depends on neocortical computations that contextually adjust sensory signals in different internal and environmental contexts. Neocortical layer 1 (LI) is the main target of cortical and subcortical inputs that provide "top-down" information for context-dependent sensory processing. Although LI is devoid of excitatory cells, it contains the distal "tuft" dendrites of pyramidal cells (PCs) located in deeper layers. LI also contains a poorly characterized population of GABAergic interneurons (INs), which regulate the impact that different top-down inputs have on PCs. A poor comprehension of LI IN subtypes and how they affect PC activity has hampered our understanding of the mechanisms that underlie contextual modulation of sensory processing. We used novel genetic strategies in male and female mice combined with electrophysiological and morphological methods to help resolve differences that were unclear when using only electrophysiological and/or morphological approaches. We discovered that LI contains four distinct populations of INs, each with a unique molecular profile, morphology, and electrophysiology, including a previously overlooked IN population (named here "canopy cells") representing 40% of LI INs. In contrast to what is observed in other layers, most LI neurons appear to be unique to the layer, highlighting the specialized character of the signal processing that takes place in LI. This new understanding of INs in LI, as well as the application of genetic methods based on the markers described here, will enable investigation of the cellular and circuit mechanisms of top-down processing in LI with unprecedented detail. [ABSTRACT FROM AUTHOR]

The interactions of several neurotransmitter and neural hormone molecules with the c-MYC G-quadruplex DNA sequence were analyzed using a combination of spectroscopic and computational techniques. The interactions between indole, catecholamine, and amino acid neurotransmitters and DNA sequences could potentially add to the understanding of the role of G-quadruplex structures play in various diseases. Also, the interaction of the DNA sequence derived from the nuclear hypersensitivity element (NHE) III 1 region of c-MYC oncogene (Pu22), 5′-TGAGGGTGGGTAGGGTGGGTAA-3′, has added significance in that these molecules may promote or inhibit the formation of G-quadruplex DNA which could lead to the development of promising drugs for anticancer therapy. The results showed that these molecules did not disrupt G-quadruplex formation even in the absence of quadruplex-stabilizing cations. There was also evidence of concentration-dependent binding and high binding affinities based on the Stern-Volmer model, and thermodynamically favorable interactions in the form of hydrogen-bonding and interactions involving the π system of the aromatic neurotransmitters. • Interaction between neurotransmitters and c-myc G-quadruplex DNA. • Spectroscopic determination of binding between quadruplex DNA and neurotransmitters. • Preservation of DNA structural integrity upon binding to neurotransmitters. [ABSTRACT FROM AUTHOR]

While many inferences have been made about the low degree of genetic variation among intra specific populations of Clitoria ternatea L. (CT), pharmacognostic biochemical investigations using tandem mass spectrometry have never been conducted. Methanol leaf extract of Clitoria ternatea L., populations collected from 13 different agro-climatic zones of India was assessed for identification and characterization of targeted nootropic metabolites, using liquid chromatography tandem mass spectrometry product ion scanning (LC-MS2 PIS). Based on the RI values derived from LC-MS2 (PIS) superior population(s), in terms of the presence of the presence of nootropic metabolites, were identified. The intra-specific correlation among different populations, was analyzed through PCA (principal component analysis), scree plot, correlation matrix and hierarchical cluster analysis. The targeted mass spectrum obtained by tandem mass spectrometric analysis revealed the presence of acetylcholine, choline, caffeic acid, gallic acid, ferulic acid, kaempferol and D-L valine mass fragments in the leaf of CT. These mass groups are belonging to four classes viz., phenols, flavonoids, neurotransmitters and amino acids. Based on the high degree of relative intensities of targeted nootropic metabolites, the Odisha population, collected from Cuttack, outperformed the rest of twelve populations. Correlation matrix data also revealed that populations habituated in similar climatic conditions show significant correlation with each other. Hierarchical cluster analysis classified the 13 populations in two groups. The first group contained 11 populations and the second group is restrained into two populations; one from Cuttack, Odisha and second one from Udaipur, Rajasthan. This is the first report to identify the superior population of Clitoria ternatea L. across India, through multivariate statistical analysis of LC-MS2(PIS) for gallic acid, ferulic acid, caffeic acid, kaempferol, D- L -valine, acetylcholine, and choline. Even though earlier studies reported an enhancement of acetylcholine content in the central nervous system. The present work may explain that the plant is a producer of acetylcholine and choline itself so it can directly affect the memory and cognition of the brain. Simultaneously, the study confirms the presence of abovementioned seven nootropic metabolites in the leaf of CT. The Odisha population (collected from Cuttack) transcends over all other 12 populations, with highest RI values of seven nootropic metabolites. According to hierarchical cluster analysis, two populations, viz., the one collected from Cuttack, Odisha and the other collected from Udaipur, Rajasthan were distantly clustered from other eleven populations. Hence, both these populations should be given priority for pharmaceutical supply and value chain management systems. • References format in the text and references part should be followed the author's guidelines. • Lines 320–321,333-336 should be in the analysis method section. • Some spelling mistakes are still found (as in line 231), please check the whole manuscript and the format also. • The abstract should be revised from its present form and should address the main conclusions based on your findings from the existing and projected states. • In my opinion, author should create and include a flow diagram in the material and method section. • The changes in the text and references are to be shown in red font in the revised manuscript for easy identification. • line 321 on page 17. The authors here to clearly bringing out software 'IBM SPSS V22′. [ABSTRACT FROM AUTHOR]

ICB was an international and dynamic research institute directed by Nobel laureate Prof. Rita-Levi-Montalcini, who was Vittorio's co-mentor during his PhD thesis. At ICB, Vittorio worked for 4 years with Prof. Giulio Levi as a student and continued to collaborate with him for a number of years after his PhD. Vittorio continues to dedicate a large proportion of his time to one of his greatest passions - mentoring of graduate students, postdoctoral fellows, and clinician scientists at different stages of their careers. [Extracted from the article]

Background: Plasma amino acid neurotransmitter dysregulation is suggested to be implicated in the development of ischemic stroke, but its prognostic value for ischemic stroke remains controversial., Objective: We aimed to prospectively investigate the associations between plasma amino acid neurotransmitters levels and adverse outcomes after ischemic stroke in a large-scale multicenter cohort study., Methods: We measured 4 plasma amino acid neurotransmitters (glutamic acid, aspartic acid, gamma-aminobutyric acid, and glycine) among 3486 patients with ischemic stroke from 26 hospitals across China. The primary outcome is the composite outcome of death or major disability (modified Rankin Scale score ≥3) at 3 mo after ischemic stroke., Results: After multivariate adjustment, the odds ratios of death or major disability for the highest versus the lowest quartile were 2.04 (95% confidence interval [CI]: 1.60,2.59; P-trend < 0.001) for glutamic acid, 2.03 (95% CI: 1.59, 2.59; P-trend < 0.001) for aspartic acid, 1.35 (95% CI: 1.06, 1.71; P-trend = 0.016) for gamma-aminobutyric acid, and 0.54 (95% CI: 0.42, 0.69; P-trend < 0.001) for glycine. Each standard deviation increment of log-transformed glutamic acid, aspartic acid, gamma-aminobutyric acid, and glycine was associated with a 34%, 34%, and 9% increased risk, and a 23% decreased risk of death or major disability, respectively (all P < 0.05), in a linear fashion as indicated by spline regression analyses (all P for linearity < 0.05). Addition of the 4 plasma amino acid neurotransmitters to conventional risk factors significantly improved the risk reclassification, as evidenced by integrated discrimination improvement and net reclassification improvement (all P < 0.05)., Conclusions: Increased glutamic acid, aspartic acid, and gamma-aminobutyric acid and decreased glycine in plasma are associated with adverse outcomes after ischemic stroke, suggesting that plasma amino acid neurotransmitters may be potential intervention targets for improving prognosis of ischemic stroke. The CATIS trial was registered at clinicaltrials.gov (registration number: NCT01840072; URL: ===https://clinicaltrials.gov/ct2/show/NCT01840072?cond=NCT01840072&draw=2&rank=1)., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Bio‐based industries need efficient downstream solutions to process complex streams. This was addressed through a technology integration approach, where expanded‐bed adsorption (EBA) is integrated with simulated moving‐bed (SMB) technology. Current work involved adaptation of an SMB apparatus and control principle to implement expanded‐bed level control. As an outcome, EBA‐SMB technology was successfully applied for purification of γ‐aminobutyric acid (GABA). This resulted in two‐fold increase in productivity and a GABA purity ≥ 92 % in one step from unclarified fermentation broth, compared to ≥ 93 % purity in case of clarified broth and packed‐bed SMB. These results proved that EBA‐SMB technology is able to enhance process efficiency and economics of bioprocesses. Effective downstream solutions are required to process complex streams in bio‐based industries. An integration approach is proposed involving expanded‐bed adsorption and simulated moving‐bed technology. This innovative combination was successfully applied for purification of γ‐aminobutyric acid, thus proving its great potential in enhancing process efficiency and economics of bioprocesses. [ABSTRACT FROM AUTHOR]

The extensive use of mobile phones worldwide has raised increasing concerns about the effects of electromagnetic radiation (EMR) on the brain due to the proximity of the mobile phone to the head and the appearance of several adverse neurological effects after mobile phone use. It has been hypothesized that the EMR-induced neurological effects may be mediated by amino acid neurotransmitters. Thus, the present study investigated the effect of EMR (frequency 1800 MHz, specific absorption rate 0.843 W/kg, power density 0.02 mW/cm2, modulated at 217 Hz) on the concentrations of amino acid neurotransmitters (glutamic acid, aspartic acid, gamma aminobutyric acid, glycine, taurine, and the amide glutamine) in the hippocampus, striatum, and hypothalamus of juvenile and young adult rats. The juvenile and young adult animals were each divided into two groups: control rats and rats exposed to EMR 1 h daily for 1, 2, and 4 months. A subgroup of rats were exposed daily to EMR for 4 months and then left without exposure for 1 month to study the recovery from EMR exposure. Amino acid neurotransmitters were measured in the hippocampus, striatum, and hypothalamus using high-performance liquid chromatography. Exposure to EMR induced significant changes in amino acid neurotransmitters in the studied brain areas of juvenile and young adult rats, being more prominent in juvenile animals. It could be concluded that the alterations in amino acid neurotransmitters induced by EMR exposure of juvenile and young adult rats may underlie many of the neurological effects reported after EMR exposure including cognitive and memory impairment and sleep disorders. Some of these effects may persist for some time after stopping exposure. [ABSTRACT FROM AUTHOR]

Abstract The aim of this review is to present and discuss the research work reported in the literature on the use of glutamic acid and its derivatives as corrosion inhibitors for metals in different aggressive solutions. Mass loss and electrochemical techniques were among the most often used techniques to evaluate the corrosion inhibition efficiency of the used inhibitor. Glutamic acid can act as an efficient corrosion inhibitor, but it can in other cases show an opposite effect, which accelerates the corrosion process; all depend on the experimental conditions. Highest values of inhibition efficiency were obtained in the presence of ions as Zn2+ and ions halides. Glutamic acid derivatives have shown a good ability to use it as an effective corrosion inhibitor for metal in an acidic solution. The development of computational modeling helps to design new glutamic acid derivatives and to understand the inhibition mechanism of those compounds. [ABSTRACT FROM AUTHOR]

Odor-guided behaviors, including homing, predator avoidance, or food and mate searching, are ubiquitous in animals. It is only recently that the neural substrate underlying olfactomotor behaviors in vertebrates was uncovered in lampreys. It consists of a neural pathway extending from the medial part of the olfactory bulb (medOB) to locomotor control centers in the brainstem via a single relay in the caudal diencephalon. This hardwired olfactomotor pathway is present throughout life and may be responsible for the olfactory-induced motor behaviors seen at all life stages. We investigated modulatory mechanisms acting on this pathway by conducting anatomical (tract tracing and immunohistochemistry) and physiological (intracellular recordings and calcium imaging) experiments on lamprey brain preparations. We show that the GABAergic circuitry of the olfactory bulb (OB) acts as a gatekeeper of this hardwired sensorimotor pathway. We also demonstrate the presence of a novel olfactomotor pathway that originates in the non-medOB and consists of a projection to the lateral pallium (LPal) that, in turn, projects to the caudal diencephalon and to the mesencephalic locomotor region (MLR). Our results indicate that olfactory inputs can induce behavioral responses by activating brain locomotor centers via two distinct pathways that are strongly modulated by GABA in the OB. The existence of segregated olfactory subsystems in lampreys suggests that the organization of the olfactory system in functional clusters may be a common ancestral trait of vertebrates. [ABSTRACT FROM AUTHOR]

Several studies have been implicated oxidative stress and genotoxicity as important mechanisms of toxic effects of pyrethriods in the present study. The beneficial effects of vitamin E and green tea extract were tested in protecting the deltamethrin (DM) induced oxidative stress, genotoxicity and alterations in some amino acid neurotransmitters in brain of adult female rats .Rats were exposed to 1mg/Kg b.wt deltamethrin (1/10 LD50 ) alone or in combination with vitamin E and/or green tea extract .The antioxidant such as catalse enzyme, reduced glutathione content, lipid peroxidation content and ChE activity were analyzed in cerebrum and cerebellum of brain excised at the end of experiment (30 days). Results showed that genotoxic effect of deltamethrin was proved by SSCP of HRas and P53 genes .Amino acids transmitters were estimated in brain of exposed DM rats . Exposure to deltamethrin resulted in a significant decrease in the activities of catalase, ChE and concentration of reduced glutathione, while the LPO levels were significantly increased in different brain regions .Also, DM exposure increases significant changes in brain amino acids. It is Interestingly that the supplementation with vitamin E or green tea extract or both resulted reversed in the deltamethrin induced antioxidant enzymes and effect on genotoxicity .Combination of both green tea and vit. E appeared to be more effective in protection than each one alone [ABSTRACT FROM AUTHOR]

Healthy aging is accompanied by motor inhibition deficits that involve a slower process of stopping a prepotent motor response (i.e., reactive inhibition) rather than a diminished ability to anticipate stopping (i.e., proactive inhibition). Some studies suggest that efficient motor inhibition is related to GABAergic function. Since age-related alterations in the GABA system have also been reported, motor inhibition impairments might be linked to GABAergic alterations in the cortico-subcortical network that mediates motor inhibition. Thirty young human adults (mean age, 23.2 years; age range, 18-34 years; 14 men) and 29 older human adults (mean age, 67.5 years; age range, 60-74 years; 13 men) performed a stop-signal task with varying levels of stop-signal probability. GABA+levels were measured with magnetic resonance spectroscopy (MRS) in right inferior frontal cortex, pre-supplementary motor area (pre-SMA), left sensorimotor cortex, bilateral striatum, and occipital cortex. We found that reactive inhibition was worse in older adults compared with young adults, as indicated by longer stop-signal reaction times (SSRTs). No group differences in proactive inhibition were observed as both groups slowed down their response to a similar degree with increasing stop-signal probability. The MRS results showed that tissue corrected GABA+ levels were on average lower in older as compared with young adults. Moreover, older adults with lower GABA+ levels in the pre-SMA were slower at stopping (i.e., had longer SSRTs). These findings suggest a role for the GABA system in reactive inhibition deficits. [ABSTRACT FROM AUTHOR]

Background and aim: Irisin is a new myokine that is secreted by myocytes during exercise, and plays a role in creating the beneficial effects of exercise on metabolism. Considering the benefits of exercise in reducing pain, this study was carried out to determine the probable effect of irisin on neuropathic pain in the chronic constriction injury (CCI) model in male rats. Methods To induce neuropathic pain CCI model was used. Animals were divided into groups of control, CCI, sham, CCI + vehicle, and CCI + irisin. Animals that had undergone CCI were divided into 6 groups and each received a different intrathecal dose of irisin (30, 10, 3, 1, 0.3, and 0.1 μg/kg) via intrathecal administration. To evaluate the chronic effect of irisin, its effective dose was injected for 14 days in another group of animals. At the end of the experiment, animals were ranscardially perfused and their spinal cord tissue was prepared for immunohistochemical and hematoxylin-eosin staining. Results The results showed that in acute intrathecal injection of irisin, 1 μg/kg dose has the highest analgesic effect compared to other doses. Nevertheless, in chronic administration of irisin with 1 μg/kg dose, no analgesic effect was detected. In addition, irisin administration could not increase the expression level of GABAB1 and B2 or prevent the decline in the number of neurons. Conclusion The findings of the present study showed that acute administration of Irisin increases the pain threshold, but the chronic injection of resin does not have an effect on pain reduction and the expression of GABA receptors and it seems that this peptide is not a proper replacement for exercise in patients with neuropathic pain, who cannot exercise. [ABSTRACT FROM AUTHOR]

Autistic traits are normally distributed across health and disease, with autism spectrum disorders (ASD) at the extreme end. As we learned from mutations of synaptic or synapse regulating genes, leading to monogenetic forms of autism, the heterogeneous etiologies of ASD converge at the synapse. They result in a mild synaptic dysfunction as the final common pathway, also addressed as synaptopathy. Based on genetic rodent models and EEG/MEG findings in autists, a neuronal excitation-inhibition dysbalance is considered autism-pathognomonic. We hypothesized that this objectively measurable consequence is not restricted to the diagnosis of ASD but transcends disease borders and is of quantitative rather than qualitative nature. For proof-of-principle, we conducted a transcranial magnetic stimulation (TMS) study, monitoring corticospinal excitability and intracortical inhibition of the motor cortex. Employing the GRAS data collection of N > 1200 deep-phenotyped schizophrenic subjects, we had the chance to select for this study N = 20 perfectly matched men. They differed highly significantly by autistic trait severity, as assessed using PANSS autism severity score (PAUSS) , capturing the continuum of autistic behaviors. Applying TMS to these men, we provide first intriguing hints of a positive correlation of autistic phenotype severity with functional cortical correlates, mainly alterations in GABAergic system and ion channels. This ‘dose-response relationship’ between severity of autistic traits and excitation-inhibition ratio in non-ASD subjects underlines the biological basis of this continuous trait. Based on these data, TMS may evolve as new add-on biomarker of autistic traits across disease groups. Finally, common treatment strategies targeting the excitation-inhibition dysbalance in humans may develop. To ultimately achieve this goal, however, replication studies with larger numbers of individuals would be desirable. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy (TLE) is present in 30% of epileptic patients and does not respond to conventional treatments. Bone marrow derived mesenchymal stem cells (BMSCs) induce endogenous neural stem cells, inhibit neurodegeneration, and promote brain self-repair mechanisms. The present study addresses the feasibility of BMSCs transplantation against pilocarpine-induced TLE experimentally. BMSCs were injected either intravenously (IV) or in hippocampus bilaterally (IC). Increased cell count of BMSCs was achieved via IC route. BMSCs treatment ameliorated the pilocarpine-induced neurochemical and histological changes, retained amino acid neurotransmitters to the normal level, downregulated the immunoreactivity to insulin growth factor-1 receptor, synaptophysin, and caspase-3 and reduced oxidative insult and inflammatory markers detected in epileptic model. It is worth noting that BMSCs IC-administered showed more pronounced effects than those administered via IV route. BMSCs transplantation presents a promise for TLE treatment that has to be elucidated clinically. [ABSTRACT FROM AUTHOR]

Corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN) are integratory hubs that regulate the endocrine response to stress. GABA inputs provide a basal inhibitory tone that constrains this system and circulating glucocorticoids (CORT) are important feedback controllers of CRH output. Surprisingly little is known about the direct effects of CORT on GABA synapses in PVN. Here we used whole-cell patch clamp recordings from CRH neurons in mouse hypothalamic brain slices to examine the effects of CORT on synaptic and extrasynaptic GABA signalling.We show that GABA transporters (GATs) limit constitutive activation of presynaptic GABAB receptors and ensure high release probability at GABA synapses. GATs in combination with GABAB receptors also curtail extrasynaptic GABAAR signalling. CORT has no effect on synaptic GABA signalling, but increases extrasynaptic GABA tone through upregulation of postsynaptic GABAA receptors. Thesedata showthat efficient GABA clearance and autoinhibition control the balance between synaptic (phasic) and extrasynaptic (tonic) inhibition in PVN CRH neurons. This balance is shifted towards increased extrasynaptic inhibition by CORT. [ABSTRACT FROM AUTHOR]

GABA is a robust regulator of both developing and mature neural networks. It exerts many of its effects through GABAA receptors, which are heteropentamers assembled from a large array of subunits encoded by distinct genes. In mammals, there are 19 different GABAA subunit types, which are divided into the α, β, γ, δ, ε, π, θ and ρ subfamilies. The immense diversity of GABAA receptors is not fully understood. However, it is known that specific isoforms, with their distinct biophysical properties and expression profiles, tune responses to GABA. Although larval zebrafish are well-established as a model system for neural circuit analysis, little is known about GABAA receptors diversity and expression in this system. Here, using database analysis, we show that the zebrafish genome contains at least 23 subunits. All but the mammalian θ and ε subunits have at least one zebrafish ortholog, while five mammalian GABAA receptor subunits have two zebrafish orthologs. Zebrafish contain one subunit, β4, which does not have a clear mammalian ortholog. Similar to mammalian GABAA receptors, the zebrafish α subfamily is the largest and most diverse of the subfamilies. In zebrafish there are eight α subunits, and RNA in situ hybridization across early zebrafish development revealed that they demonstrate distinct patterns of expression in the brain, spinal cord, and retina. Some subunits were very broadly distributed, whereas others were restricted to small populations of cells. Subunit-specific expression patterns in zebrafish resembled were those found in frogs and rodents, which suggests that the roles of different GABAA receptor isoforms are largely conserved among vertebrates. This study provides a platform to examine isoform specific roles of GABAA receptors within zebrafish neural circuits and it highlights the potential of this system to better understand the remarkable heterogeneity of GABAA receptors. [ABSTRACT FROM AUTHOR]

Drought‐induced reduction of leaf gas exchange entails a complex regulation of the plant leaf metabolism. We used a combined molecular and physiological approach to understand leaf photosynthetic and respiratory responses of 2‐year‐old Quercus ilex seedlings to drought. Mild drought stress resulted in glucose accumulation while net photosynthetic CO2 uptake (Pn) remained unchanged, suggesting a role of glucose in stress signaling and/or osmoregulation. Simple sugars and sugar alcohols increased throughout moderate‐to‐very severe drought stress conditions, in parallel to a progressive decline in Pn and the quantum efficiency of photosystem II; by contrast, minor changes occurred in respiration rates until drought stress was very severe. At very severe drought stress, 2‐oxoglutarate dehydrogenase complex gene expression significantly decreased, and the abundance of most amino acids dramatically increased, especially that of proline and γ‐aminobutyric acid (GABA) suggesting enhanced protection against oxidative damage and a reorganization of the tricarboxylic cycle acid cycle via the GABA shunt. Altogether, our results point to Q. ilex drought tolerance being linked to signaling and osmoregulation by hexoses during early stages of drought stress, and enhanced protection against oxidative damage by polyols and amino acids under severe drought stress. [ABSTRACT FROM AUTHOR]

Glycine-extended gastrin 17 (G17-Gly), a dominant processing intermediate of gastrin gene, has been implicated in the development or maintenance of colorectal cancers (CRCs). Hence, neutralizing G17-Gly activity by antibody entities can provide a potential therapeutic strategy in the patients with CRCs. To this end, we isolated fully human antibody fragments from a phage antibody library through biopanning against different epitopes of G17-Gly in order to obtain the highest possible antibody diversity. ELISA screening and sequence analysis identified 2 scFvs and 4 VL antibody fragments. Kinetic analysis of the antibody fragments by SPR revealed KD values to be in the nanomolar range (87.9-334 nM). The selected anti-G17-Gly antibody fragments were analyzed for growth inhibition and apoptotic assays in a CRC cell line, HCT-116, which is well-characterized for expressing gastrin intermediate species but not amidated gastrin. The antibody fragments exhibited significant inhibition of HCT-116 cells proliferation ranging from 36.5 to 73% of controls. Further, Annexin V/PI staining indicated that apoptosis rates of scFv H8 and VL G8 treated cells were 45.8 and 63%, respectively. Based on these results, we for the first time, demonstrated the isolation of anti-G17-Gly human scFv and VL antibodies with potential therapeutic applications in G17-Gly-responsive tumors. [ABSTRACT FROM AUTHOR]

Dates are commercially consumed as semi-dried fruit or processed into juice and puree for further food production. However, the date residue after juice and puree production is not used, although it appears to be nutrient enriched. Here, date residue was fermented by a lactic acid bacterium, Lactobacillus brevis , which has been generally recognized as safe. Through degradation of sodium glutamate added to the residue during the fermentation, γ-aminobutyric acid (GABA), which reduces neuronal excitability, was produced at the conversion rate of 80–90% from glutamate. In order to achieve this GABA production level, pretreatment of the date residue with carbohydrate-degrading enzymes, i.e., cellulase and pectinase, was necessary. All ingredients used for this GABA fermentation were known as being edible. These results provide us with a solution for the increasing commercial demand for GABA in food industry with the use of date residue that has been often discarded. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is classically characterized as a movement disorder, however cognitive impairments precede the motor symptoms by ∼15 y. Based on proteomic and bioinformatic data linking the Huntingtin protein (Htt) and KCC2, which is required for hyperpolarizing GABAergic inhibition and the important role of inhibition in learning and memory, we hypothesized that aberrant KCC2 function contributes to the hippocampal-associated learning and memory deficits in HD. We discovered that Htt and KCC2 interact in the hippocampi of wild-type and R6/2-HD mice, with a decrease in KCC2 expression in the hippocampus of R6/2 and YAC128 mice. The reduced expression of the Cl-extruding cotransporter KCC2 is accompanied by an increase in the Cl-importing cotransporter NKCC1, which together result in excitatory GABA in the hippocampi of HD mice. NKCC1 inhibition by the FDA-approved NKCC1 inhibitor bumetanide abolished the excitatory action of GABA and rescued the performance of R6/2 mice on hippocampalassociated behavioral tests. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an autoimmune disease with the impaired balance of CD4+T cells. This trial is a descriptive study to evaluate the expression of CD4+T cell cytokines, interleukin (IL) -2, IL-4, IL-17, TGF-β, and respectively related transcription factors, including T-bet, GATA3, RORγt and FoxP3 in MS patients. Sixteen relapsing-remitting MS (RRMS) patients receiving interferon beta (IFN-β)-1a in the stable phase of the disease and 14 healthy control volunteers (HCs) were enrolled in this study. The expression of cytokines and transcription factors was evaluated in peripheral blood mononuclear cells (PBMCs) of patients using real time PCR. The results of this study showed that the expression of IL-2 (P≤0.05), IL-4 (P≤0.05), IL- 17 (P≤0.05) and RORγt (P≤0.01) in PBMCs of RRMS patients were significantly higher than those in HCs. The expression of TGF-β, GATA3, and FoxP3 were higher but the RORγt expression was lower in the patients than HCs without reaching significant value. Observed results indicated differences in immune system cytokines of healthy volunteers and the patients that were in the stable phase and under immunomodulatory therapy especially in proinflammatory mediators. Therefore, any therapeutic strategy to restore the immune system balance is desirable in RRMS patients. [ABSTRACT FROM AUTHOR]