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Introduction: Changpu Yujin Tang(CPYJT), a Chinese herbal compound, is an effective therapeutic strategy for pediatric patients with Tourette disorder (TD). Therefore, this work aims to investigate the therapeutic mechanisms of CPYJT. Methods: Behavioral and cellular ultrastructural evaluation of the therapeutic effects of CPYJT in TD model rats. Colorimetric methods, reverse transcription‑quantitative PCR, and Western Blot were used to measure the altered levels of GLU, GABA, and the levels of VGLUT1, GLUD1, GABRA3, and GAD65 in the cortex, striatum, and thalamus of the TD model rats after 7, 14, 21, and 28 days of CPYJT administration. Results: CPYJT significantly reduced stereotypic behavior and motor behavior scores in TD model rats. CPYJT ameliorates myelin structural damage in TD model rat neuronal cells. CPYJT decreased GLU content, elevated GABA content, decreased GLUD1 and VGLUT1 levels, and elevated GAD65 and GABRA3 levels in TD model rats' cortex, striatum, and thalamus. CPYJT has different regulatory time points in the cortex, striatum, and thalamus for critical factors of amino acid-based neurotransmission. Conclusion: CPYJT protects behavioral and structural damage of neuronal cells in multiple brain regions in TD model rats. [ABSTRACT FROM AUTHOR]

Objective: Although accumulating evidence implicating altered gut microbiota in human immunodeficiency virus (HIV) infection and neurodegenerative disorders; however, the association between dysbiosis of the gut microbiota and metabolites in the pathogenesis of HIV‐associated neurocognitive disorder (HAND) remains unclear. Methods: Fecal and plasma samples were obtained from 3 cohorts (HAND, HIV–non‐HAND, and healthy controls), metagenomic analysis and metabolomic profiling were performed to investigate alterations in the gut microbial composition and circulating metabolites in HAND. Results: The gut microbiota of people living with HIV (PLWH) had an increased relative abundance of Prevotella and a decreased relative abundance of Bacteroides. In contrast, Prevotella and Megamonas were substantially decreased, and Bacteroides and Phocaeicola were increased in HAND patients. Moreover, untargeted metabolomics identified several neurotransmitters and certain amino acids associated with neuromodulation, and the differential metabolic pathways of amino acids associated with neurocognition were depleted in HAND patients. Notably, most neuromodulatory metabolites are associated with an altered abundance of specific gut bacteria. Interpretation: Our findings provide new insights into the intricate interplay between the gut and microbiome‐brain axis in the pathogenesis of HAND, highlighting the potential for developing novel therapeutic strategies that specifically target the gut microbiota. ANN NEUROL 2024;96:306–320 [ABSTRACT FROM AUTHOR]

Neurotransmitters carrying specific chemical information play a key role in the nervous system, which inspires ion‐based devices to mimic biological functions of nervous system, including sensing, transduction, and computing. In this work, the interaction mechanism of zwitterionic amino acids, glycine (Gly), and gamma‐aminobutyric acid (GABA) (two common inhibitory neurotransmitters) are analyzed with porous carbon electrodes. The charge balance of these zwitterionic neurotransmitters relies on zwitterion protonation in the vicinity of the negative electrodes (produced cations adsorbed by the negative electrode) and deprotonation near the positive electrode (produced anions to balance the positive charges) as demonstrated based on the theoretical dissociation analyses and local pH measurements. Additionally, electrosorption‐induced concentration changes of Gly and GABA in aqueous solutions and phosphate‐buffered saline (PBS) solutions are realized by electrosorption via nanoporous carbon electrodes. Based on this mechanistic understanding, the ionologic functions in printed ionic electrolyte double‐layer transistors are demonstrated. These neurotransmitter‐based iontronic devices hold potential for further organism‐machine interfacing and neuromorphic computing applications. [ABSTRACT FROM AUTHOR]

Amino acid neurotransmitters, including glutamate, phenylalanine, tyrosine, alanine, and glycine, underlie the majority of the excitatory and inhibitory neurotransmission in the nervous system, and acute exercise has been shown to modulate their concentrations. We aimed to determine whether any correlation exists between the above-mentioned amino acid blood concentrations and the neuropsychological performance after an acute exercise intervention. Sixty basketball players were randomly assigned to one of two experimental conditions: exercise or inactive resting. All participants underwent a comprehensive neuropsychological assessment and blood samples were taken on a Guthrie card before and after the end of the experimental conditions. Amino acid blood concentrations were significantly elevated and cognitive performance significantly improved post-exercise on specific neuropsychological assessments. Significant intervention × group interaction effects were apparent for Trail Making Test part-B [F(1,58) = 20.46, p <.0001, η2 =.26] and Digit Span Backwards [F(1,58) = 15.47, p <.0001, η2 =.21] neuropsychological assessments. Additionally, regression analysis indicated that tyrosine accounted for 38.0% of the variance in the Trail Making Test part-A test. These results suggest that elevated blood concentrations of neurotransmission-related amino acids are associated with improved neuropsychological performance after a single bout of high-intensity exercise. [ABSTRACT FROM AUTHOR]

Glycine plays a pivotal role in the Central Nervous System (CNS), being a major inhibitory neurotransmitter as well as a co-agonist of Glutamate at excitatory NMDA receptors. Interactions involving Glycine and other neurotransmitters are the subject of different studies. Functional interactions among neurotransmitters include the modulation of release through release-regulating receptors but also through transporter-mediated mechanisms. Many transporter-mediated interactions involve the amino acid transmitters Glycine, Glutamate, and GABA. Different studies published during the last two decades investigated a number of transporter-mediated interactions in depth involving amino acid transmitters at the nerve terminal level in different CNS areas, providing details of mechanisms involved and suggesting pathophysiological significances. Here, this evidence is reviewed also considering additional recent information available in the literature, with a special (but not exclusive) focus on glycinergic neurotransmission and Glycine–Glutamate interactions. Some possible pharmacological implications, although partly speculative, are also discussed. Dysregulations in glycinergic and glutamatergic transmission are involved in relevant CNS pathologies. Pharmacological interventions on glycinergic targets (including receptors and transporters) are under study to develop novel therapies against serious CNS pathological states including pain, schizophrenia, epilepsy, and neurodegenerative diseases. Although with limitations, it is hoped to possibly contribute to a better understanding of the complex interactions between glycine-mediated neurotransmission and other major amino acid transmitters, also in view of the current interest in potential drugs acting on "glycinergic" targets. [ABSTRACT FROM AUTHOR]

The article in the Journal of Neurology highlights the life and contributions of American biochemist Morris H. Aprison, who co-discovered the role of glycine as a neurotransmitter. Aprison's research also focused on the neurochemical correlates of behavior, the excitatory action of aspartate and glutamate, and molecular mechanisms of transmitter-receptor interactions. His work laid the foundation for understanding neurotransmission and its impact on behavior, earning him recognition in the field of neurochemistry. [Extracted from the article]

The editorial discusses the role of monoamines in mood disorders, emphasizing the importance of autoregulatory mechanisms, cross-interactions between different monoamines, and crosstalk with other bioactive molecules. International researchers contributed articles on various topics related to monoamines, including endocannabinoid-monoamine interactions, neurochemical mechanisms of psychedelics, and interactions between monoamines, glutamate, and endogenous opioids. The research highlights the complexity of neurotransmitter interactions and their implications for understanding and treating mental disorders. [Extracted from the article]

Modern life is filled with radiofrequency electromagnetic radiation (RF-EMR) in various frequency bands, while the health risks are not clear. In this study, mice were whole-body exposed to 0.9/1.5/2.65 GHz radiofrequency radiation at 4 W/kg for 2 h per day for 4 weeks to investigate the emotional effects. It was found that the mice showed anxiety but no severe depression. The ELISA results showed a significant decrease in amino acid neurotransmitters (GABA, DA, 5-HT), although acetylcholine (ACH) levels were not significantly altered. Furthermore, Western blot results showed that BDNF, TrkB, and CREB levels were increased in the cerebral cortex, while NF-κB levels were decreased. In addition, pro-inflammatory factors (IL-6, IL-1β, TNF-α) were significantly elevated, and anti-inflammatory factors (IL-4, IL-10) tended to decrease. In conclusion, multi-frequency electromagnetic radiation induces an inflammatory response through the CREB-BDNF-TrkB and NF-κB pathways in the cerebral cortex and causes a decrease in excitatory neurotransmitters, which ultimately causes anxiety in mice. [ABSTRACT FROM AUTHOR]

Iridoid components have been reported to have significant neuroprotective effects. However, it is not yet clear whether the efficacy and mechanisms of iridoid components with similar structures are also similar. This study aimed to compare the neuroprotective effects and mechanisms of eight iridoid components (catalpol (CAT), genipin (GE), geniposide (GEN), geniposidic acid (GPA), aucubin (AU), ajugol (AJU), rehmannioside C (RC), and rehmannioside D (RD)) based on corticosterone (CORT)-induced injury in PC12 cells. PC12 cells were randomly divided into a normal control group (NC), model group (M), positive drug group (FLX), and eight iridoid administration groups. Firstly, PC12 cells were induced with CORT to simulate neuronal injury. Then, the MTT method and flow cytometry were applied to evaluate the protective effects of eight iridoid components on PC12 cell damage. Thirdly, a cell metabolomics study based on ultra-performance liquid chromatography–quadrupole–time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was performed to explore changes in relevant biomarkers and metabolic pathways following the intervention of administration. The MTT assay and flow cytometry analysis showed that the eight iridoid components can improve cell viability, inhibit cell apoptosis, reduce intracellular ROS levels, and elevate MMP levels. In the PCA score plots, the sample points of the treatment groups showed a trend towards approaching the NC group. Among them, AU, AJU, and RC had a weaker effect. There were 38 metabolites (19 metabolites each in positive and negative ion modes, respectively) identified as potential biomarkers during the experiment, among which 23 metabolites were common biomarkers of the eight iridoid groups. Pathway enrichment analysis revealed that the eight iridoid components regulated the metabolism mainly in relation to D-glutamine and D-glutamate metabolism, arginine biosynthesis, the TCA cycle, purine metabolism, and glutathione metabolism. In conclusion, the eight iridoid components could reverse an imbalanced metabolic state by regulating amino acid neurotransmitters, interfering with amino acid metabolism and energy metabolism, and harmonizing the level of oxidized substances to exhibit neuroprotective effects. [ABSTRACT FROM AUTHOR]

Epilepsy is a recurring neurological disease caused by the abnormal electrical activity in the brain. This disease has caused about 50 new cases in 100,000 populations every year with the clinical manifestations of awareness loss, bruising, and mobility abnormalities. Due to the lack understanding of the pathophysiology behind the illness, a wide variety of medications are available to treat epilepsy. Epileptogenesis is the process by which a normally functioning brain undergoes alterations leading to the development of epilepsy, involving various factors. This is related to the inflammation which is driven by cytokines like IL-1 and tumor necrosis factor-α (TNF-α) leads to neuronal hyperexcitability. Pro-inflammatory cytokines from activated microglia and astrocytes in epileptic tissue initiate an inflammatory cascade, heightening neuronal excitability and triggering epileptiform activity. The blood-brain barrier (BBB) maintains central nervous system integrity through its tight endothelial connections, but inflammation impact BBB structure and function which leads to immune cell infiltration. The mammalian target of rapamycin (mTOR) pathway's excessive activation influences epileptogenesis, impacting neuronal excitability, and synapse formation, with genetic mutations contributing to epilepsy syndromes and the modulation of autophagy playing a role in seizure onset. The apoptotic pathway contribute to cell death through glutamate receptor-mediated excitotoxicity, involving pro-apoptotic proteins like p53 and mitochondrial dysfunction, leading to the activation of caspases and the disruption of calcium homeostasis. Ionic imbalances within neural networks contribute to the complexity of epileptic seizures, involving alterations in voltage-gated sodium and potassium channels, and the formation of diverse ion channel subtypes. Epileptogenesis triggers molecular changes in hippocampus, including altered neurogenesis and enhanced expression of neurotrophic factors and proteins. Oxidative stress leads to cellular damage, disrupted antioxidant systems, and mitochondrial dysfunction, making it a key player in epileptogenesis and potential neuroprotective interventions. Thalamocortical circuitry disruption is central to absence epilepsy, the normal circuit becomes faulty and results in characteristic brain wave patterns. [ABSTRACT FROM AUTHOR]

Objective: Dementias and mild cognitive impairment (MCI) are associated with variously combined changes in the neurotransmitter system and signaling, from neurotransmitter synthesis to synaptic binding. The study tested the hypothesis that different dementia subtypes and MCI may share similar reductions of brain availability in amino acid precursors (AAPs) of neurotransmitter synthesis and concomitant similar impairment in energy production and increase of oxidative stress, i.e., two important metabolic alterations that impact neurotransmission. Materials and methods: Sixty-five demented patients (Alzheimer's disease, AD, n = 44; frontotemporal disease, FTD, n = 13; vascular disease, VaD, n = 8), 10 subjects with MCI and 15 control subjects (CTRL) were recruited for this study. Cerebrospinal fluid (CSF) and plasma levels of AAPs, energy substrates (lactate, pyruvate), and an oxidative stress marker (malondialdehyde, MDA) were measured in all participants. Results: Demented patients and subjects with MCI were similar for age, anthropometric parameters, biohumoral variables, insulin resistance (HOMA index model), and CSF neuropathology markers. Compared to age-matched CTRL, both demented patients and MCI subjects showed low CSF AAP tyrosine (precursor of dopamine and catecholamines), tryptophan (precursor of serotonin), methionine (precursor of acetylcholine) limited to AD and FTD, and phenylalanine (an essential amino acid largely used for protein synthesis) (p = 0.03 to <0.0001). No significant differences were found among dementia subtypes or between each dementia subtype and MCI subjects. In addition, demented patients and MCI subjects, compared to CTRL, had similar increases in CSF and plasma levels of pyruvate (CSF: p = 0.023 to <0.0001; plasma: p < 0.002 to <0.0001) and MDA (CSF: p < 0.035 to 0.002; plasma: p < 0.0001). Only in AD patients was the CSF level of lactate higher than in CTRL (p = 0.003). Lactate/pyruvate ratios were lower in all experimental groups than in CTRL. Conclusion: AD, FTD, and VaD dementia patients and MCI subjects may share similar deficits in AAPs, partly in energy substrates, and similar increases in oxidative stress. These metabolic alterations may be due to AAP overconsumption following high brain protein turnover (leading to phenylalanine reductions), altered mitochondrial structure and function, and an excess of free radical production. All these metabolic alterations may have a negative impact on synaptic plasticity and activity. [ABSTRACT FROM AUTHOR]

Context Jing-an oral liquid (JA) is a Chinese herbal formula used in the treatment of Tourette syndrome (TS); however, its mechanism is unclear.Objective To investigate the effects of JA on amino acid neurotransmitters and microglia activation in vivo and in vitro.Materials and methods Sixty male Sprague–Dawley rats were divided into a control group and 5 TS groups. TS was induced in rats with intraperitoneal injection of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (1 mg/kg) and in BV2 cells with lipopolysaccharide. Control and model rats were administered saline, whereas treatment groups were administered JA (5.18, 10.36, or 20.72 g/kg) or tiapride (a benzamide, 23.5 mg/kg) by gavage once daily for 21 days. Stereotypic behaviour was tested. The levels of N-methyl-d-aspartate receptor (NMDAR)/mitogen-activated protein kinase/cAMP response element-binding protein (CREB)-related proteins in striatum and BV2 cells were measured via western blots. CD11b and IBa1 levels were also measured. Ultra-high-performance liquid-chromatography was used to determine γ-aminobutyric acid (GABA), glutamic acid (Glu), and aspartic acid (ASP) levels.Results JA markedly alleviated the stereotype behaviour (25.92 ± 0.35 to 13.78 ± 0.47) in rats. It also increased NMDAR1 (0.48 ± 0.09 to 0.67 ± 0.08; 0.54 ± 0.07 to 1.19 ± 0.18) expression and down-regulated the expression of p-ERK, p-JNK, p-P38, and p-CREB in BV2 cells and rat striatum. Additionally, Glu, ASP, GABA, CD11b, and IBa1 levels were significantly decreased by JA.Discussion and conclusions JA suppressed microglia activation and regulated the levels of amino acid neurotransmitters, indicating that it could be a promising therapeutic agent for TS.

Despite the usage of nanoparticles (NPs) is rapidly increasing, several experts have noted the risk of their release into ecosystems and their potential negative impacts on biological systems. However, the available studies on the neurobehavioral impacts of aluminum oxide nanoparticles (Al2O3NPs) on aquatic organisms are little. Hence, this study targeted to ascertain the harmful effects of Al2O3NPs on behavioral characteristics and genotoxic and oxidative damages in Nile tilapia fish. In addition, the beneficial role of chamomile essential oil (CEO) supplementation in reducing these effects was also investigated. In the current study, fish were distributed into 4 equal groups (n = 60 fish per group). The control group was fed a plain diet only, the CEO group received a basic diet complemented with CEO at a level of 2 mg/kg diet, the ALNP group received a basic diet and was exposed to an approximate concentration of 1/10th LC50 of ALNPs nearly 5.08 mg/L, and the combination group (ALNPs/CEO group) received a basal diet coadministered with ALNPs and CEO at the aforementioned percentages. The findings revealed that O. niloticus exhibit neurobehavioral changes along with changes in the level of GABA, monoamines in the brain tissue, and serum amino acid neurotransmitters, besides a reduction of AChE and Na+/K+-ATPase activities. In addition to brain tissue oxidative damage with upregulation of proinflammatory and stress genes, such as HSP70 and caspase-3, supplementation of CEO significantly reduced the negative impacts of ALNPs. These results showed that CEO has neuroprotective, antioxidant, genoprotective, anti-inflammatory, and antiapoptotic properties in fish that have been exposed to ALNPs. Therefore, we advise its usage as a valuable addition to fish diet. [ABSTRACT FROM AUTHOR]

Zebrafish (Danio rerio) assays provide a versatile pharmacological platform to test compounds on a wide range of behaviors in a whole organism. A major challenge lies in the lack of knowledge about the bioavailability and pharmacodynamic effects of bioactive compounds in this model organism. Here, we employed a combined methodology of LC-ESI-MS/MS analytics and targeted metabolomics with behavioral experiments to evaluate the anticonvulsant and potentially toxic effects of the angular dihydropyranocoumarin pteryxin (PTX) in comparison to the antiepileptic drug sodium valproate (VPN) in zebrafish larvae. PTX occurs in different Apiaceae plants traditionally used in Europe to treat epilepsy but has not been investigated so far. To compare potency and efficacy, the uptake of PTX and VPN into zebrafish larvae was quantified as larvae whole-body concentrations together with amino acids and neurotransmitters as proxy pharmacodynamic readout. The convulsant agent pentylenetetrazole (PTZ) acutely reduced the levels of most metabolites, including acetylcholine and serotonin. Conversely, PTX strongly reduced neutral essential amino acids in a LAT1 (SLCA5)-independent manner, but, similarly to VPN specifically increased the levels of serotonin, acetylcholine, and choline, but also ethanolamine. PTX dose and time-dependent manner inhibited PTZ-induced seizure-like movements resulting in a ~70% efficacy after 1 h at 20 µM (the equivalent of 4.28 ± 0.28 µg/g in larvae whole-body). VPN treated for 1 h with 5 mM (the equivalent of 18.17 ± 0.40 µg/g in larvae whole-body) showed a ~80% efficacy. Unexpectedly, PTX (1–20 µM) showed significantly higher bioavailability than VPN (0.1–5 mM) in immersed zebrafish larvae, possibly because VPN in the medium dissociated partially to the readily bioavailable valproic acid. The anticonvulsive effect of PTX was confirmed by local field potential (LFP) recordings. Noteworthy, both substances specifically increased and restored whole-body acetylcholine, choline, and serotonin levels in control and PTZ-treated zebrafish larvae, indicative of vagus nerve stimulation (VNS), which is an adjunctive therapeutic strategy to treat refractory epilepsy in humans. Our study demonstrates the utility of targeted metabolomics in zebrafish assays and shows that VPN and PTX pharmacologically act on the autonomous nervous system by activating parasympathetic neurotransmitters. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Converging lines of evidence suggest that dysfunction of cortical GABAergic inhibitory interneurons is a core feature of psychosis. This dysfunction is thought to underlie neuroimaging abnormalities commonly found in patients with psychosis, particularly in the hippocampus. These include increases in resting cerebral blood flow (CBF) and glutamatergic metabolite levels, and decreases in ligand binding to GABAA α5 receptors and to the synaptic density marker synaptic vesicle glycoprotein 2A (SV2A). However, direct links between inhibitory interneuron dysfunction and these neuroimaging readouts are yet to be established. Conditional deletion of a schizophrenia susceptibility gene, the tyrosine kinase receptor Erbb4 , from cortical and hippocampal inhibitory interneurons leads to synaptic defects, and behavioral and cognitive phenotypes relevant to psychosis in mice. Study Design Here, we investigated how this inhibitory interneuron disruption affects hippocampal in vivo neuroimaging readouts. Adult Erbb4 conditional mutant mice (Lhx6-Cre;Erbb4 F/F , n = 12) and their wild-type littermates (Erbb4 F/F , n = 12) were scanned in a 9.4T magnetic resonance scanner to quantify CBF and glutamatergic metabolite levels (glutamine, glutamate, GABA). Subsequently, we assessed GABAA receptors and SV2A density using quantitative autoradiography. Results Erbb4 mutant mice showed significantly elevated ventral hippccampus CBF and glutamine levels, and decreased SV2A density across hippocampus sub-regions compared to wild-type littermates. No significant GABAA receptor density differences were identified. Conclusions These findings demonstrate that specific disruption of cortical inhibitory interneurons in mice recapitulate some of the key neuroimaging findings in patients with psychosis, and link inhibitory interneuron deficits to non-invasive measures of brain function and neurochemistry that can be used across species. [ABSTRACT FROM AUTHOR]

The main objective of the present study was to determine metabolic profile changes in the brains of rats after simulated heliox saturated diving (HSD) to 400 meters of sea water compared to the blank controls. Alterations in the polar metabolome in the rat brain due to HSD were investigated in cortex, hippocampus, and striatum tissue samples by applying an NMR-based metabolomic approach coupled with biochemical detection in the cortex. The reduction in glutathione and taurine levels may hypothetically boost antioxidant defenses during saturation diving, which was also proven by the increased malondialdehyde level, the decreased superoxide dismutase, and the decreased glutathione peroxidase in the cortex. The concomitant decrease in aerobic metabolic pathways and anaerobic metabolic pathways comprised downregulated energy metabolism, which was also proven by the biochemical quantification of the metabolic enzymes Na-K ATPase and LDH in cerebral cortex tissue. The significant metabolic abnormalities of amino acid neurotransmitters, such as GABA, glycine, and aspartate, decreased aromatic amino acids, including tyrosine and phenylalanine, both of which are involved in the metabolism of dopamine and noradrenaline, which are downregulated in the cortex. Particularly, a decline in the level of N-acetyl aspartate is associated with neuronal damage. In summary, hyperbaric decompression of a 400 msw HSD affected the brain metabolome in a rat model, potentially including a broad range of disturbing amino acid homeostasis, metabolites related to oxidative stress and energy metabolism, and destabilizing neurotransmitter components. These disturbances may contribute to the neurochemical and neurological phenotypes of HSD. [ABSTRACT FROM AUTHOR]

Amino acids are important in several biochemical pathways as precursors to neurotransmitters which impact biological processes previously linked to functional gastrointestinal disorders (FGIDs). Dietary protein consumption, metabolic host processes, and the gut microbiome can influence the plasma concentration of amino acids and neurotransmitters, and their uptake by tissues. The aim of this analysis was to quantify 19 proteogenic and 4 non-proteogenic amino acids and 19 neurotransmitters (including precursors and catabolites, herein referred to as neurotransmitters) to ascertain if their circulating concentrations differed between healthy participants and those with FGIDs. Plasma proteogenic and non-proteogenic amino acids and neurotransmitters were measured using ultra-performance liquid chromatography and liquid chromatography–mass spectrometry, respectively, from 165 participants (Rome IV: irritable bowel syndrome (IBS-constipation, IBS-diarrhea), functional constipation, functional diarrhea, and healthy controls). There were significant differences (p < 0.05) in pairwise comparisons between healthy controls and specific FGID groups for branched-chain amino acids (BCAAs), ornithine, and alpha-aminobutyric acid. No other significant differences were observed for the neurotransmitters or any other amino acids analyzed. Multivariate and bivariate correlation analyses between proteogenic and non-proteogenic amino acids and neurotransmitters for constipation (constipation (IBS-C and functional constipation) and phenotypes diarrhea (IBS-D and functional diarrhea)) and healthy controls suggested that associations between BCAAs, 5-hydroxytryptophan, and kynurenine in combination with tyrosine, 3,4-dihydroxyphenylalanine, and 3,4-dihydroxyphenylacetic acid and associations with gamma-aminobutyric acid, glutamate, asparagine, and serine are likely disrupted in FGID phenotypes. In conclusion, although correlations were evident between some proteogenic and non-proteogenic amino acids and neurotransmitters, the results showed minor concentration differences in plasma proteogenic and non-proteogenic amino acids, amino acid-derived metabolites, and neurotransmitters between FGID phenotypes and healthy controls. [ABSTRACT FROM AUTHOR]

Objective: To study the extraction process of agarwood active ingredients (AA) and investigate the safety and effectiveness of AA in the treatment of insomnia rats by nasal administration. Method: A β-cyclodextrin (β-CD) inclusion compound (a-β-CD) was prepared from agarwood essential oil (AEO), and the preparation process was optimized and characterized. The safety of AA in nasal mucosa was evaluated through Bufo gargarizans maxillary mucosa and rat nasal mucosa models. Insomnia animal models were replicated by injecting p-chlorophenylalanine (PCPA), conducting behavioral tests, and detecting the expression levels of monoamine neurotransmitters (NE and 5-HT) and amino acids (GABA/Glu) in the rat hypothalamus. Results: The optimum inclusion process conditions of β-CD were as follows: the feeding ratio was 0.35:1.40 (g:g), the inclusion temperature was 45 °C, the inclusion time was 2 h, and the ICY% and IEO% were 53.78 ± 2.33% and 62.51 ± 3.21%, respectively. The inclusion ratio, temperature, and time are the three factors that have significant effects on the ICY% and IEO% of a-β-CD. AA presented little damage to the nasal mucosa. AA increased the sleep rate, shortened the sleep latency, and prolonged the sleep time of the rats. The behavioral test results showed that AA could ameliorate depression in insomnia rats to a certain extent. The effect on the expression of monoamine neurotransmitters and amino acids in the hypothalamus of rats showed that AA could significantly reduce NE levels and increase the 5-HT level and GABA/Glu ratio in the hypothalamus of insomnia rats. Conclusion: The preparation of a-β-CD from AEO can reduce its irritation, improve its stability, increase its curative effect, and facilitate its storage and transport. AA have certain therapeutic effects on insomnia. The mechanism of their effect on rat sleep may involve regulating the expression levels of monoamine neurotransmitters and amino acids in the hypothalamus. [ABSTRACT FROM AUTHOR]

Scavenger receptor class B type 1 (SR−B1), a multiligand membrane receptor, is expressed in a gradient along the gastrocolic axis. SR−B1 deficiency enhances lymphocyte proliferation and elevates inflammatory cytokine production in macrophages. However, whether SR−B1 affects intestinal metabolites is unclear. In this study, we detected metabolite changes in the intestinal tissue of SR−B1−/− mice, including amino acids and neurotransmitters, by ultra−performance liquid chromatography quadrupole time−of−flight mass spectrometry (UHPLC−Q−TOF/MS) and HPLC. We found that SR−B1−/− mice exhibited changes in intestinal lipid metabolites and metabolic pathways, including the glycerophospholipid, sphingolipid, linoleic acid, taurine, and hypotaurine metabolic pathways. SR−B1 deficiency influenced the contents of amino acids and neurotransmitters in all parts of the intestine; the contents of leucine (LEU), phenylalanine (PHE), tryptophan (TRP), and tyrosine (TYR) were affected in all parts of the intestine; and the contents of 3,4−dihydroxyphenylacetic acid (DOPAC) and dopamine (DA) were significantly decreased in both the colon and rectum. In summary, SR−B1 deficiency regulated intestinal lipids, amino acids, and neurotransmitter metabolism in mice. [ABSTRACT FROM AUTHOR]

l -theanine has been shown to have a therapeutic effect on depression. However, whether l -theanine has an excellent preventive effect on depression in children and adolescents and what its mechanism is have not been well explained. Given the complexity of the pathogenesis of depression, this study investigated the preventive effect and mechanism of l -theanine on depression in juvenile rats by combining serum and hippocampal metabolomic strategies. Behavioral tests, hippocampal tissue sections, and serum and hippocampal biochemical indexes were studied, and the results confirmed the preventive effect of l -theanine. Untargeted reversed-phase liquid chromatography-quadrupole-time-of-flight mass spectrometry and targeted hydrophilic interaction liquid chromatography-triple quadrupole mass spectrometry were developed to analyze the metabolism changes in the serum and hippocampus to screen for potential biomarkers related to l -theanine treatment. The results suggested that 28 abnormal metabolites in the serum and hippocampus that were considered as potential biomarkers returned to near-normal levels after l -theanine administration. These biomarkers were involved in various metabolic pathways, mainly including amino acid metabolism and lipid metabolism. The levels of amino acids and neurotransmitters in the phenylalanine, tryptophan, and glutamic acid pathways were significantly reduced after l -theanine administration compared with chronic unpredictable mild stress-induced rats. In summary, l -theanine had a significant preventive effect on depression and achieved its preventive results on depression by regulating various aspects of the body, such as amino acids, lipids, and inflammation. This research systematically analyzed the mechanism of l -theanine in preventing depression and laid the foundation for applying l -theanine to prevent depression in children and adolescents. [Display omitted] • The mechanism of theanine in prevention of depression based on metabolomics was studied for the first time. • Simultaneous untargeted and targeted metabolomics studies in CUMS-induced rat periphery and central nervous system. • A rapid HILIC-QQQ-MS/MS method was developed and validated for the accurate determination of altered neurotransmitters. [ABSTRACT FROM AUTHOR]

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), useful for the detection of macromolecules, is generally not suitable for recording the mass spectrum of small molecules, especially within the range of m / z 500, because of the appearance of matrix cluster peaks in the small molecular weight range. To circumvent this problem, a matrix-free variant of MALDI-MS, namely Label-assisted laser desorption/ionization mass spectrometry (LALDI-MS) has been developed in recent years where analytes get covalently attached to a laser absorbing label which induces the desorption/ionization process thus facilitating the recording the mass spectra and avoiding the problem of formation of cluster peaks. In general, the probes used for such detections are all pyrene-based scaffolds which despite being a good laser-active chromophore have both reactivity and solubility problems. Inspired by the right chromophoric nature, we have undertaken a systematic study to design and optimize cinnamaldehyde derivatives and have found that p -methoxy cinnamaldehyde (PMC) as a simpler, cost-effective, less hydrophobic laser-active label, which can detect a series of primary amines, including the neurotransmitters and amino acids. The label PMC can also discriminate between aliphatic and aromatic primary amines. Use of p -Methoxy Cinnamaldehyde in Label-assisted Laser Desorption/Ionization Mass Spectrometry (LALDI-MS) for Detection of Different Classes of Primary Amines, Amino Acids and Neurotransmitters Ekroop Kaur Cheema, Prabuddha Bhattacharya, Monisha Singha and Amit Basak. [Display omitted] • Application of a new label, p -methoxy cinnamaldehyde (PMC), in label-assisted laser desorption ionization spectrometry. • The label can detect primary amines, both aliphatic, aromatic, amino acids, and biogenic amines. • The method is free from the interference of non-aromatic molecules like glucose and ascorbic acid. • The method can detect aromatic amines like p -anisidine in the presence of aliphatic amines. • p -Methoxy cinnamaldehyde is less hydrophobic as compared to the commonly used pyrene labels and gives much cleaner spectra. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated whether 12-week intake of molecular hydrogen (H2) in 5 overweight adults (3 women; age: 50.2 ±11.9 years, body mass index: 29.4 ±2.1 kg/m2) affects brain levels of the glutamate-glutamine-GABA cycle, critical amino acid neurotransmitters in the mechanism of neuronal activation during appetite regulation. Methods: A 1.5-T single-voxel proton magnetic resonance spectroscopy was used to assess the tissue concentrations of relevant metabolites. Results: The mean glutamate and glutamate-plus-glutamine levels at the posterior cingulate gyrus decreased significantly during the study; this was accompanied by a significant drop in GABA levels at left prefrontal white matter, and glutathione levels at anterior cingulate gyrus. No changes in the brain metabolites were found in the comparable group of overweight individuals (n = 4, 2 women; age: 41.0 ±13.9, BMI 26.8 ±1.3 kg/m2) followed-up in the past without this treatment. Conclusions: We showed a possible hydrogen-driven upregulation of neurotransmitters involved in appetite stimulation leading to hunger suppression and weight loss. Further studies analyzing appetite-controlling metabolic pathways affected by H2 would require monitoring of additional biomarkers of satiation and satiety during different feeding regimens. [ABSTRACT FROM AUTHOR]

Neurotransmitter metabolism plays a critical role in the pathophysiology of major depressive disorder (MDD). However, whether the neurotransmitter metabolism in adolescent MDD is differentiated from adult MDD is still elusive. In the current study, plasma concentrations of monoamine and amino acid neurotransmitters as well as their metabolites, including tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), vanillylmandelic acid (VMA), 3-methoxy-4-hydroxyphenylglycol (MHPG), glutamine (GLN), glutamate (GLU) and gamma-aminobutyric acid (GABA), were measured and compared in two cohorts of subjects (adult cohort: 31 first-episode MDD vs. 35 healthy controls; adolescent cohort: 33 first-episode MDD vs. 30 healthy controls). To assess the effects of antidepressant treatment, we also analyzed the concentrations of these indexes pre- and post-treatment in adult and adolescent cohorts. At baseline, the deficits of neurotransmitter metabolism in adult MDD were manifested in all the neurotransmitter systems. In contrast, for adolescent MDD, the dysregulation of neurotransmission was mainly indicated in the catecholaminergic systems. After antidepressant treatment, adult MDD showed increased TRP, KYN, KYNA and GLU levels, together with decreased levels of 5-HIAA and DOPAC. Adolescent MDD illustrated an increased level of 5-HT and decreased levels of TRP and GABA. The improvements of Hamilton total scores correlated with the changes in plasma TRP and the turnover of KYN/TRP after treatment in all MDD patients. However, these correlations were only manifested in the adult MDD rather than in adolescent MDD patients. The findings highlight the shared and distinguished neurotransmitter pathways in MDD and emphasize the different antidepressant responses between adults and adolescents. Potentially, the neurotransmitters above could serve as diagnostic biomarkers and provide a novel pharmacological treatment strategy for MDD. [ABSTRACT FROM AUTHOR]

Chlorpyrifos and cyfluthrin are insecticides commonly used in agriculture. The mixed residues of chlorpyrifos and cyfluthrin in the aquatic environment may have combined effects on nontarget species. Therefore, studying the combined toxic effects and mechanisms of pesticide mixtures is of great significance to environmental risk assessment. To evaluate the risk of combined exposure, we examined the effects of both compounds, separately and together, on motor activity, acetylcholinesterase (AChE) activity, and neurotransmitter levels in larval zebrafish. Chlorpyrifos exposure significantly reduced functional motor capacity (swim distance and velocity) and enhanced meandering, while cyfluthrin exposure alone had no significant effects on swim parameters. However, combined exposure significantly reduced total swimming distance and mean velocity and increased meandering. Both compounds alone and the combination significantly reduced AChE activity, and the combined effect was antagonistic. Combined exposure also significantly altered the concentrations of serotonin, serotonin precursors, and dopamine precursors, as well as concentrations of the amino acid neurotransmitters glycine, alanine, and aspartic acid. Combined exposure to chlorpyrifos and cyfluthrin exhibited distinct joint action modes in terms of neurobehavior, AChE activity, and neurotransmitter levels, thereby providing an experimental basis for assessing the combined exposure to chlorpyrifos and cyfluthrin's environmental risk. [ABSTRACT FROM AUTHOR]

During an ischemic stroke, the brain releases various factors, including glutamate and γ-aminobutyric acid. Glutamate can cause neurotoxic effects through certain receptors and exacerbate neurological damage, while γ-aminobutyric acid as an inhibitory neurotransmitter can antagonize the excitotoxic effects of glutamate and enhance the tolerance of neurons to ischemia. Therefore, in this study, the content of amino acid neurotransmitters in brain tissue before ischemia, after 10 min of ischemia, hypothermic perfusion, and rewarming were analyzed by high-performance liquid chromatography-UV in an animal model of ischemic stroke generated by blocking the bilateral common carotid arteries of rhesus monkeys. The changes in amino acid neurotransmitters in the rhesus monkey brain during post-ischemia hypothermic perfusion and rewarming were investigated by statistical methods of repeated measures ANOVA, showing that the concentration change of glutamate had not only a temporal factor but also was influenced by temperature, and there was an interaction effect between the two. Time but not temperature affected the change in γ-aminobutyric acid concentration, and there was an interaction effect between the two. Accordingly, hypoperfusion exerts a protective effect during ischemia by inhibiting the release of excitatory amino acid neurotransmitters, while the antagonistic effect of GABA on Glu is not significant. [ABSTRACT FROM AUTHOR]

Background: Vagus nerve is one of the crucial routes in communication between the immune and central nervous systems. The impaired vagal nerve function may intensify peripheral inflammatory processes. This effect subsides along with prolonged recovery after permanent nerve injury. One of the results of such compensation is a normalized plasma concentration of stress hormone corticosterone -- a marker of hypothalamicpituitary-adrenal (HPA) axis activity. In this work, we strive to explain this corticosterone normalization by studying the mechanisms responsible for compensation-related neurochemical alterations in the hypothalamus. Materials and Methods: Using microarrays and high performance liquid chromatography (HPLC), we measured genome-wide gene expression and major amino acid neurotransmitters content in the hypothalamus of bilaterally vagotomized rats, 1 month after surgery. Results: Our results show that, in the long term, vagotomy affects hypothalamic amino acids concentration but not mRNA expression of tested genes. Discussion: We propose an alternative pathway of immune to CNS communication after vagotomy, leading to activation of the HPA axis, by influencing central amino acids and subsequent monoaminergic neurotransmission. [ABSTRACT FROM AUTHOR]

Introduction: Caffeine and nicotine are the most widely consumed psychostimulants worldwide. Although the effects of each drug alone on the central nervous system have been studied extensively, the literature on the neurochemical and electrophysiological effects of their combined treatments is scarce. The present study investigated the cortical electrophysiological and neurochemical alterations induced by acute administration of caffeine and nicotine in rats. Methods: The rats received caffeine and nicotine at a 1-hour interval between the two treatments. Results: Caffeine and nicotine administration resulted in a significant decrease in the concentrations of cortical amino acid neurotransmitters, namely glutamate, aspartate, glycine, and taurine, while γ-aminobutyric acid (GABA) significantly increased. Increased cortical lipid peroxidation and reduced glutathione and nitric oxide levels and acetylcholinesterase and Na⁺/K⁺-ATPase activities were also observed. The Electroencephalogram (EEG) showed an increase in delta frequency power band, whereas theta, beta-1, and beta-2 decreased after caffeine and nicotine treatment. Conclusion: These findings suggest that caffeine and nicotine adversely exacerbate their stimulant effects manifested by the EEG changes mediated by increasing cholinergic transmission and disturbing the balance between the excitatory and inhibitory amino acids leading to oxidative stress.

BackgroundVagus nerve is one of the crucial routes in communication between the immune and central nervous systems. The impaired vagal nerve function may intensify peripheral inflammatory processes. This effect subsides along with prolonged recovery after permanent nerve injury. One of the results of such compensation is a normalized plasma concentration of stress hormone corticosterone – a marker of hypothalamic-pituitary-adrenal (HPA) axis activity. In this work, we strive to explain this corticosterone normalization by studying the mechanisms responsible for compensation-related neurochemical alterations in the hypothalamus.Materials and MethodsUsing microarrays and high performance liquid chromatography (HPLC), we measured genome-wide gene expression and major amino acid neurotransmitters content in the hypothalamus of bilaterally vagotomized rats, 1 month after surgery.ResultsOur results show that, in the long term, vagotomy affects hypothalamic amino acids concentration but not mRNA expression of tested genes.DiscussionWe propose an alternative pathway of immune to CNS communication after vagotomy, leading to activation of the HPA axis, by influencing central amino acids and subsequent monoaminergic neurotransmission.

Microplastics have emerged as a prominent global environmental contaminant, and they have been found in both human placenta and breast milk. However, the potential effects and mechanisms of maternal exposure to microplastics at various gestational stages on offspring neurodevelopment remain poorly understood. This investigation delves into the potential neurodevelopmental ramifications of maternal exposure to polystyrene nanoplastics (PS-NPs) during distinct phases of pregnancy and lactation. Targeted metabolomics shows that co-exposure during both pregnancy and lactation primarily engendered alterations in monoamine neurotransmitters within the cortex and amino acid neurotransmitters within the hippocampus. After prenatal exposure to PS-NPs, fetal rats showed appreciably diminished cortical thickness and heightened cortical cell proliferation. However, this exposure did not affect the neurodifferentiation of radial glial cells and intermediate progenitor cells. In addition, offspring are accompanied by disordered neocortical migration, typified by escalated superficial layer neurons proliferation and reduced deep layer neurons populations. Moreover, the hippocampal synapses showed significantly widened synaptic clefts and diminished postsynaptic density. Consequently, PS-NPs culminated in deficits in anxiolytic-like behaviors and spatial memory in adolescent offspring, aligning with concurrent neurotransmitter and synaptic alterations. In conclusion, this study elucidates the sensitive windows of early-life nanoplastic exposure and the consequential impact on offspring neurodevelopment. [Display omitted] • PS-NPs mainly alter proliferation of offspring microglia rather than neuronal differentiation. • PS-NPs induce anti-anxiety behavior in offspring by affecting neurotransmitter levels. • PS-NPs cause spatial memory deficits in offspring by damaging synapses. • Effects of exposure during pregnancy are more severe than during lactation. [ABSTRACT FROM AUTHOR]

Although co-occurring methamphetamine (meth) use and HIV amplify the risk for neuropsychiatric comorbidities, the underlying neuroimmune mechanisms are not well characterized. We examined whether a detectable viral load and dysregulated metabolism of amino acid precursors for neurotransmitters predicted subsequent levels of sexual compulsivity and sexual sensation seeking. This 15-month longitudinal study enrolled 110 sexual minority men (SMM) living with HIV who had biologically confirmed meth use (i.e., reactive urine or hair toxicology results). Peripheral venous blood samples collected at baseline, 6 months, 12 months, and 15 months were used to measure a detectable viral load (> 40 copies/mL), the kynurenine/tryptophan (K/T) ratio, and the phenylalanine/tyrosine (P/T) ratio. The K/T and P/T ratios index dysregulated serotonin and catecholamine (e.g., dopamine) synthesis, respectively. In a cross-lagged panel model, a detectable viral load at 6 months predicted greater sexual compulsivity at 12 months after adjusting for prior levels of sexual compulsivity and recent stimulant use (β = 0.26, p = 0.046). A greater P/T ratio at baseline predicted decreased sexual sensation seeking at 6 months (β = − 0.25, p = 0.004) after adjusting for baseline sexual sensation seeking and recent stimulant use. Taken together, HIV replication and dysregulated catecholamine synthesis could potentiate sexual compulsivity while decreasing sexual pleasure in SMM who use meth. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disease that afflicts millions of people all over the world. Intracerebroventricular (ICV) injection of a sub-diabetogenic dose of streptozotocin (STZ) was established as an experimental animal model of AD. The present study was conducted to evaluate the efficacy of curcumin nanoparticles (CNs) against the behavioral, neurochemical and histopathological alterations induced by ICV-STZ. The animals were divided into: control animals, the animal model of AD that received a single bilateral ICV microinjection of STZ, and the animals protected by a daily oral administration of CNs for 6 days before the ICV-STZ injection. The animals of all groups were subjected to surgical operation on the 7th day of administration. Then the administration of distilled water or CNs was continued for 8 days. The ICV-STZ microinjection produced cognitive impairment as evident from the behavioral Morris water maze (MWM) test and induced oxidative stress in the cortex and hippocampus as indicated by the significant increases in lipid peroxidation and nitric oxide (NO) levels and the significant decrease in reduced glutathione (GSH) levels. It also produced a significant increase in acetylcholinesterase (AChE) and tumor necrosis-alpha (TNF-ɑ) and a significant decrease in Na+,K + -ATPase. In addition, a significant increase in amino acid neurotransmitters occurred in the hippocampus, whereas a significant decrease was obtained in the cortex of STZ-induced AD rats. CNs ameliorated the behavioral, immunohistochemical and most of the neurochemical alterations induced by STZ in the hippocampus and cortex. It may be concluded that CNs might be considered as a promising therapeutic agent for the treatment of AD. [ABSTRACT FROM AUTHOR]

Background: Xylazole (Xyl) is a veterinary anesthetic that is structurally and functionally similar to xylazine. However, the effects of Xyl in vitro remain unknown. Objectives: This study aimed to investigate the anesthetic mechanism of Xyl using fetal rat nerve cells treated with Xyl. Methods: Fetal rat nerve cells cultured for seven days were treated with 10, 20, 30, and 40 μg/mL Xyl for 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, and 120 min. Variations of amino acid neurotransmitters (AANTs), Nitric oxide-Cyclic GMP (NO-cGMP) signaling pathway, and ATPase were evaluated. Results: Xyl decreased the levels of cGMP and NO in nerve cells. Furthermore, Xyl affected the AANT content and Na+-K+-ATPase and Ca2+-Mg2+-ATPase activity in nerve cells. These findings suggested that Xyl inhibited the NO-cGMP signaling pathway in nerve cells in vitro. Conclusions: This study provided new evidence that the anesthetic and analgesic effects of Xyl are related to the inhibition of the NO-cGMP signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: Iminodipropionitrile (IDPN)-induced dyskinetic syndrome is characterized by abnormal repetitive involuntary movements with abnormalities in the neuro-transmission. This study explored the mechanism of glutamate (Glu)/γ-aminobutyric acid (GABA)-glutamine (Gln) metabolic circuit in rat dyskinetic syndrome and the possible regulation mechanism of "tiapride (Tia)." Methods: Male Wistar rats were assigned to the control group, dyskinetic syndrome group, and Tia group. Dyskinetic syndrome was induced by injecting with 3,3′-iminodipropionitrile for 7 days. Tia group was treated with tiapride, while the control and dyskinetic syndrome groups were gavaged with saline. Eventually the Glu, GABA, and Gln concentrations in striatum were detected using UPLC-3QMS, additionally another amino acid neurotransmitters (aspartate, glycine) were also detected. Expressions of glutamine synthetase (GS), glutamate transporter (EAAT2), glutamate decarboxylase (GAD65/67), and γ-aminobutyric acid transporter protein (GAD-T) were observed using Western blot and real-time polymerase chain reaction. Results: The behavior test scores of dyskinetic syndrome group were increased compared with the control group. Tia group decreased the behavior test scores compared with dyskinetic syndrome group. For amino acid neuro-transmission, dyskinetic syndrome group increased Glu level (p < 0.01), decreased GABA level (p < 0.01), increased Glu/GABA ratio (p < 0.01), and decreased Asp level (p < 0.01) compared with control group. Tia group decreased Glu level (p < 0.01), increased GABA level (p < 0.01), decreased Glu/GABA ratio (p < 0.01), and increased Asp level (p < 0.05) compared with dyskinetic syndrome group. For Glu/GABA-Gln circuit, the protein and mRNA expression of GS and EAAT2 in dyskinetic syndrome group were decreased (p < 0.05). Tia group increased protein and mRNA expression level of GS (p < 0.05) and EAAT2 (p < 0.01). Conclusion: The rat dyskinetic syndrome has Glu/GABA-Gln abnormalities. "Tiapride" upregulated the protein expression of GS and EAAT2, reduce Glu levels, increase γ-GABA levels, and eventually improve amino acid neurotransmitter imbalance. [ABSTRACT FROM AUTHOR]

The mammalian gut harbors a complex and dynamic microbial ecosystem: the microbiota. While emerging studies support that microbiota regulates brain function with a few molecular cues suggested, the overall biochemical landscape of the "microbiota-gut-brain axis" remains largely unclear. Here we use high-coverage metabolomics to comparatively profile feces, blood sera, and cerebral cortical brain tissues of germ-free C57BL/6 mice and their age-matched conventionally raised counterparts. Results revealed for all three matrices metabolomic signatures owing to microbiota, yielding hundreds of identified metabolites including 533 altered for feces, 231 for sera, and 58 for brain with numerous significantly enriched pathways involving aromatic amino acids and neurotransmitters. Multicompartmental comparative analyses single out microbiota-derived metabolites potentially implicated in interorgan transport and the gut-brain axis, as exemplified by indoxyl sulfate and trimethylamine-N-oxide. Gender-specific characteristics of these landscapes are discussed. Our findings may be valuable for future research probing microbial influences on host metabolism and gut-brain communication. The gut microbiota harbours neuroactive potential with links to neurological disorders. Here, the authors apply global metabolomics with an integrated annotation strategy to comparatively profile fecal, blood serum and cerebral cortical brain tissues of eight-week-old germ-free mice vs. age-matched specific-pathogen-free mice, providing a snapshot of the metabolome status linked to the gut-brain axis. [ABSTRACT FROM AUTHOR]

Amino acid neurotransmitters are responsible for many physiological and pathological processes, and their cerebral concentrations respond to external influences such as the light–dark cycle and to the synthesis, release, and recapture rhythms and form part of the biochemical relationships derived from excitatory-inhibitory (E/I), glutamine–glutamate sum (GLX), glutamatergic processing (glutamine–glutamate ratio) and excitotoxic indexes. The changes in these variables during a 24-h period (1 day) are important because they allow organisms to adapt to external stimuli and form part of physiological processes. Under pathological conditions, the damage produced by acute events may depend on diurnal variations. Therefore, it is important to analyze the extracellular levels of amino acids as well as the above-mentioned indexes over a 24-h period. We focused on determining the cerebrospinal fluid levels of different amino acid neurotransmitters, and the E/I, GLX, glutamatergic processing and excitotoxic indexes, determined by microdialysis over a 24-h cycle. Our results showed significant changes during the 24-h light/dark cycle. Specifically, we found increments in the levels of glutamate (325%), GABA (550%), glutamine (300%), glycine (194%), alanine (304%) and the GLX index (263%) throughout the day, and the maximum levels of glutamate, glutamine, glycine, and alanine were obtained during the last period of the light period. In conclusion, the concentration of some amino acid neurotransmitters and the GLX index show variations depending on the light–dark cycle. [ABSTRACT FROM AUTHOR]

Introduction: Caffeine and nicotine are the most widely consumed psychostimulants worldwide. Although the effects of each drug alone on the central nervous system have been studied extensively, the literature on the neurochemical and electrophysiological effects of their combined treatments is scarce. The present study investigated the cortical electrophysiological and neurochemical alterations induced by acute administration of caffeine and nicotine in rats. Methods: The rats received caffeine and nicotine at a 1-hour interval between the two treatments. Results: Caffeine and nicotine administration resulted in a significant decrease in the concentrations of cortical amino acid neurotransmitters, namely glutamate, aspartate, glycine, and taurine, while γ-aminobutyric acid (GABA) significantly increased. Increased cortical lipid peroxidation and reduced glutathione and nitric oxide levels and acetylcholinesterase and Na+/K+-ATPase activities were also observed. The Electroencephalogram (EEG) showed an increase in delta frequency power band, whereas theta, beta-1, and beta-2 decreased after caffeine and nicotine treatment. Conclusion: These findings suggest that caffeine and nicotine adversely exacerbate their stimulant effects manifested by the EEG changes mediated by increasing cholinergic transmission and disturbing the balance between the excitatory and inhibitory amino acids leading to oxidative stress. [ABSTRACT FROM AUTHOR]

Background: The New Zealand Green-lipped mussel industry is well-established providing vastly to aquaculture exports. To assess mussel health and reproduction status, visual examination of organs and/or collection of haemolymph is commonly applied. Anesthetics, such as magnesium chloride (MgCl2) can be utilized to prevent muscle contraction and keep shells open during sampling. The specific effects of muscle relaxing agents on baseline metabolism in invertebrates is unknown, but it is evident that molecular, cellular and physiological parameters are altered with these chemical applications. To this end, metabolomics approaches can help elucidate the effects of relaxing agents for better assessment of their use as a research tool. Methods: Adult Green-lipped mussels were anaesthetized for 3 h in a MgCl2 bath, whereafter haemolymph samples were collected and analyzed via gas chromatography–mass spectrometry applying methyl chloroformate alkylation derivatization. Results: Anesthetized mussels were characterized as non-responsive to manual manipulation, with open valves, and limited siphoning function. Metabolite profiling revealed significant increases in the abundances of most metabolites with an array of metabolic activities affected, resulting in an energy imbalance driven by anaerobic metabolism with altered amino acids acting as neurotransmitters and osmolytes. Conclusion: This research is the first to use a metabolomics approach to identify the metabolic consequences of this commonly used bivalve relaxing technique. Ultimately the use of MgCl2 anesthetization as a sampling strategy should be carefully evaluated and managed when performing metabolomics-related research. [ABSTRACT FROM AUTHOR]

Calix[n]arenes, as the 'third-generation' host molecules, are cyclic oligomer, featuring a unique three-dimensional structure with a hydrophobic cavity, allowing the interaction with many size-matched guest molecules, and a surface which can be functionalised at both the upper and lower rims with several functional groups to tailor the recognition properties towards a specific class of analytes for various applications. In the last two decades, due to their configuration, unique molecule recognition function and aggregation properties, calixarenes and their derivatives have attracted considerable attention as a new versatile scaffold for highly sensitive detection and site-oriented immobilisation in biosensor development. In this review, the development of sensors featuring calixarene-based transducers tuned for binding many analytes, ranging from simple (i.e., amino acids and neurotransmitters) to complex (i.e., enzymes and antibodies) organic molecules, was described. The rational design, the synthetic strategies fine-tuned to prepare these complex structures and their grafting in surface modification were included. [ABSTRACT FROM AUTHOR]

An increase in plasma l-methionine (Met) levels, even if transitory, can cause important toxicological alterations in the affected individuals. Met is essential in the regulation of epigenetic mechanisms and its influence on the subsequent generation has been investigated. However, few studies have explored the influence of a temporary increase in Met levels in parents on their offspring. This study evaluated the behavioral and neurochemical effects of parental exposure to high Met concentration (3 mM) in zebrafish offspring. Adult zebrafish were exposed to Met for 7 days, maintained for additional 7 days in tanks that contained only water, and then used for breeding. The offspring obtained from these fish (F1) were tested in this study. During the early stages of offspring development, morphology, heart rate, survival, locomotion, and anxiety-like behavior were assessed. When these animals reached the adult stage, locomotion, anxiety, aggression, social interaction, memory, oxidative stress, and levels of amino acids and neurotransmitters were analyzed. F1 larvae Met group presented an increase in the distance and mean speed when compared to the control group. F1 adult Met group showed decreased anxiety-like behavior and locomotion. An increase in reactive oxygen species was also observed in the F1 adult Met group whereas lipid peroxidation and antioxidant enzymes did not change when compared to the control group. Dopamine, serotonin, glutamate, and glutathione levels were increased in the F1 adult Met group. Taken together, our data show that even a transient increase in Met in parents can cause behavioral and neurochemical changes in the offspring, promoting transgenerational effects. [ABSTRACT FROM AUTHOR]

As an important psychoactive substance, cotinine is ubiquitous in aquatic environment and poses a threat to aquatic organisms. However, the mechanism of its adverse health impacts remains unclear. We evaluated the effects of cotinine exposure at environmentally relevant concentrations on the development and locomotor behavior of zebrafish (Danio rerio) larvae using neurotransmitters and whole endogenous metabolism. Mild developmental toxicity and significant neurobehavior disorder, such as spontaneous movement (1–1000 μg/L), 48 hpf tactile response (50, 100, and 1000 μg/L), and 144 hpf swimming speed (1, 10, 100, 500, and 1000 μg/L), were observed in zebrafish. Exposure to cotinine led to significant alterations in 11 neurotransmitters, including homogentisic acid, serotonin, glutamic acid and aspartic acid, etc. 298 metabolites were identified and two pathways - linoleic acid metabolism and taurine and hypotaurine metabolism - were delineated. In addition, amino acid neurotransmitters were significantly correlated with metabolites such as arachidonic acid as well as its derivatives, steroidal compounds, and amino acids. Serotonin demonstrates a noteworthy correlation with 31 out of 40 differentially expressed neurotransmitters, encompassing lipids, amino acids, and other compounds. These novel findings contribute to a comprehensive understanding of the ecological risks associated with cotinine contamination in surface waters. [Display omitted] • Cotinine induced developmental and neurobehavioral toxicity in zebrafish. • Cotinine disturbed linoleic acid metabolism in zebrafish. • Cotinine disturbed neurotransmitters and metabolites in zebrafish. • Arachidonic acid metabolites linked amino acid neurotransmitters significantly. [ABSTRACT FROM AUTHOR]

There is compelling evidence of a causal link between chronic stress and the sympathetic system as well as the HPA axis (hypothalamus-pituitary-adrenal axis) and emotional disorders. Emotional disorders, depression, neuromodulator, HPA axis, stress Keywords: emotional disorders; depression; neuromodulator; HPA axis; stress EN emotional disorders depression neuromodulator HPA axis stress 1 4 4 06/28/21 20210624 NES 210624 Psychological processes include two equally important aspects of mental processes: cognition and emotion, emotional disorders might account for more than 90% of mental disorders. [Extracted from the article]

Mood disorders represent a pressing public health issue and significant source of disability throughout the world. The classical monoamine hypothesis, while useful in developing improved understanding and clinical treatments, has not fully captured the complex nature underlying mood disorders. Despite these shortcomings, the monoamine hypothesis continues to dominate the conceptual framework when approaching mood disorders. However, recent advances in basic and clinical research have led to a greater appreciation for the role that amino acid neurotransmitters play in the pathophysiology of mood disorders and as potential targets for novel therapies. In this article we review progress of compounds that focus on these systems. We cover both glutamate-targeting drugs such as: esketamine, AVP-786, REL-1017, AXS-05, rapastinel (GLYX-13), AV-101, NRX-101; as well as GABA-targeting drugs such as: brexanolone (SAGE-547), ganaxolone, zuranolone (SAGE-217), and PRAX-114. We focus the review on phase-II and phase-III clinical trials and evaluate the extant data and progress of these compounds. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that amino acid (AA) neurotransmitters play important roles in the pathophysiological processes of cerebral ischemia. In this work, an HPLC with fluorescence detection (HPLC‐FLR) method was developed for the simultaneous determination of 18 AAs in the cortex and plasma after cerebral ischemia in mice. The ischemia model was prepared by bilateral common carotid artery occlusion, and then the cortex and plasma of the sham, ischemia, and naringenin groups were collected. Based on the protein precipitation method, a simple and effective sample preparation method was developed. The treated sample contained minimal proteins and lipids. The analysis of the sample was performed by the proposed HPLC‐FLR method in combination with o‐phthalaldehyde. The results showed a statistically significant increase in excitatory AAs (aspartic acid and glutamic acid), inhibitory AAs (glycine and 4‐aminobutyric acid), phenylalanine, citrulline, isoleucine, and leucine levels, and a decrease of glutathione and phenylalanine levels when compared with the sham group in the cortex. Besides, the administration of naringenin had significant effects on excitatory AAs, inhibitory AA (glycine), glutamine, tyrosine, phenylalanine, and leucine levels when compared with the sham group in the cortex. These findings could be utilized in studying and clarifying the mechanisms of ischemia. [ABSTRACT FROM AUTHOR]

"Glial cells are in the brain to support neurons" is one of the commonplaces taught at regular lectures by neuroscientists to future generations of neurobiologists. Adding Schwann cells, satellite glia, enteric glia, and glial cells of sensory organs to this list is a thrilling reminder that an amazing variety of glial cell types not only exists at around 1:1 ratio but works in unison in the human nervous systems to allow it to reach its computational, intellectual, and emotional power that makes us unique. Here, we introduce B Alexei Verkhratsky b and B Arthur M. Butt b as two of the most eminent glia biologists of our time whose new book, titled " B Neuroglia: Function and Pathology b " is a wonderfully illustrated, comprehensive, thematic, and insightful account of the vast knowledge that has accumulated on glial cells of both the central and peripheral nervous systems over the past ~150 years. [Extracted from the article]