Striatum-enriched protein, arginase 2 localizes to medium spiny neurons and controls striatal metabolic profile.

Arginase 2 (Arg2) is the predominant arginase isoenzyme in the brain, however its distribution appears to be limited to selected, region-specific subpopulations of cells. Although striatum is highly enriched with Arg2, precise localization and function of striatal Arg2 have never been studied. Here, we confirm that Arg2 is the only arginase isoenzyme in the striatum, and, using genetic model of total Arg2 loss, we show that Arg2 in this region is fully responsible for arginase catalytic activity, and its loss doesn't induce compensatory activation of Arg1.

Exposure of cerebellar granule cells to nanosilver: Oxidative stress parameters and the protective effect of exogenous glutathione.

In recent decades, the production of silver nanoparticles (AgNPs) has shown exponential growth. They are widely used as high-potency antimicrobial agents in a range of medical and consumer products and increasingly in the agricultural sector as a component of plant protection nanoproducts. Due to the risk of environmental hazards, the mechanisms of AgNPs toxicity should be thoroughly investigated to deepen our understanding of the potential negative impact on human health.

Metabolic Biomarkers Differentiate a Surgical Intervertebral Disc from a Nonsurgical Intervertebral Disc.

Background: Degeneration of the intervertebral disc (IVD) is caused by disturbances in metabolic processes, which lead to structural disorders. The aim of this report is to analyze metabolic disorders in the degeneration process by comparing control discs with degenerated discs. In our research on the nucleus pulposus (NP), we used NMR spectroscopy of extracts of hydrophilic and hydrophobic compounds of the tissue.

NMR-Based Metabolomics of Rat Hippocampus, Serum, and Urine in Two Models of Autism.

Autism spectrum disorders (ASDs) are increasingly diagnosed as developmental disabilities of unclear etiology related to genetic, epigenetic, or environmental factors. The diagnosis of ASD in children is based on the recognition of typical behavioral symptoms, while no reliable biomarkers are available. Rats in whom ASD-like symptoms are due to maternal administration of the teratogenic drugs valproate or thalidomide on critical day 11 of pregnancy are widely used models in autism research.

Serum metabolic profiles and metal levels of patients with multiple sclerosis and patients with neuromyelitis optica spectrum disorders - NMR spectroscopy and ICP-MS studies.

Background And Objectives: Neuromyelitis optica spectrum disorder (NMOSD) is a disease misdiagnosed with multiple sclerosis (MS). We hypothesized that the serum metabolic profile could be helpful in the differentiation of both diseases in an early stage.

Methods: We included controls, patients with MS diagnosed according to the McDonald criteria of 2010, and patients with NMOSD diagnosed according to the criteria from 2015.

Zinc and Copper Brain Levels and Expression of Neurotransmitter Receptors in Two Rat ASD Models.

Zinc and copper are important trace elements necessary for the proper functioning of neurons. Impaired zinc and/or copper metabolism and signaling are implicated in many brain diseases, including autism (ASD). In our studies, autistic-like behavior in rat offsprings was induced by application to pregnant mothers valproic acid or thalidomide.

Peptide Dendrimers with Non-Symmetric Bola Structure Exert Long Term Effect on Glioblastoma and Neuroblastoma Cell Lines.

Background: Glioblastoma (GBM) is the most common malignant tumor of the central nervous system (CNS). Neuroblastoma (NB) is one of the most common cancers of childhood derived from the neural crest cells. The survival rate for patients with GBM and high-risk NB is poor; therefore, novel therapeutic approaches are needed.

The effects of exercise training on lipid profile in patients with sarcoidosis.

This study aimed to determine the use of lipid profiling to assess the effects of moderate intensity exercise training (ET) on patients with sarcoidosis. Fourteen patients with sarcoidosis (mean age, 46.0 ± 9.

Changes in the metabolic profiles of the serum and putamen in Parkinson's disease patients - In vitro and in vivo NMR spectroscopy studies.

The aim of this study was to investigate the relationship between serum metabolomic biomarkers and brain in vivo magnetic resonance spectroscopy (MRS) biomarkers in patients with Parkinson's disease (PD) as well as to investigate compound concentration changes by comparing the results with healthy control subjects. Univariate statistical analysis of the serum showed significant differences in the levels of phenylalanine, tyrosine, lysine, glutamine, glutamate, acetone, acetate, 3-hydroxybutyrate, and 1-monoacylglycerol (1-MAG) between the PD patient group and the control group. Orthogonal partial least squares discriminant analysis showed significantly different compound concentrations of acetate, 3-hydroxybutyrate, glutamine, tyrosine, 1-MAG and testosterone.

Hippocampal Metabolite Profiles in Two Rat Models of Autism: NMR-Based Metabolomics Studies.

Autism spectrum disorders (ASDs) are increasingly being diagnosed. Hypotheses link ASD to genetic, epigenetic, or environmental factors. The role of oxidative stress and the imbalance between excitatory and inhibitory neurotransmission in the pathogenesis of ASD has been suggested.

Altered expression of glutamatergic and GABAergic genes in the valproic acid-induced rat model of autism: A screening test.

Autism spectrum disorders (ASD) include neurodevelopmental disorders in which behavioral deficits can result from neuronal imbalance of excitation to inhibition (E/I) in the brain. Here we used RT-qPCR to screen for the expression of 99 genes associated with excitatory (glutamatergic) and inhibitory (GABAergic) neurotransmission in the cerebral cortex, hippocampus and cerebellum of rats in an established VPA model of ASD. The largest changes in the expression of glutamatergic genes were found in the cerebral cortex, where 12 genes including these encoding some of the subunits of the ionotropic glutamate receptors, were upregulated, while 2 genes were downregulated.

Changes in the Expression of SNAP-25 Protein in the Brain of Juvenile Rats in Two Models of Autism.

The results of genetic studies suggest a possible role for SNAP-25 polymorphism in the development of autism spectrum disorders (ASDs); however, there are no data available on whether changes in SNAP-25 expression also affect animals in rodent models of ASD. The aim of the present study was to explore this issue. The studies included 1-month-old rats representing valproic acid (VPA)- and thalidomide (THAL)-induced models of autism.

Altered Cerebrospinal Fluid Concentrations of Hydrophobic and Hydrophilic Compounds in Early Stages of Multiple Sclerosis-Metabolic Profile Analyses.

The lack of a single predictive or diagnostic test in multiple sclerosis (MS) remains a major obstacle in the patient's care. The aim of this study was to investigate metabolic profiles, especially lipids in cerebrospinal fluid (CSF) using H-NMR spectroscopy and metabolomics analysis to discriminate MS patient group from the control ones. In this study, 19 MS patients and 19 controls, without neurological problems, patients were enrolled.

Molecular Antioxidant Properties and In Vitro Cell Toxicity of the -Aminobenzoic Acid (PABA) Functionalized Peptide Dendrimers.

Exposure to ozone level and ultraviolet (UV) radiation is one of the major concerns in the context of public health. Numerous studies confirmed that abundant free radicals initiate undesired processes, e.g.

Tetrabromobisphenol A-induced depolarization of rat cerebellar granule cells: ex vivo and in vitro studies.

The brominated flame retardant tetrabromobisphenol A (TBBPA) is toxic to cultured brain neurons, and glutamate receptors partially mediate this effect; consequently, the depolarizing effect of TBBPA on neurons is to be expected, but it is yet to be actually demonstrated. The aim of this study was to detect TBBPA-evoked depolarization and identify the underlying mechanisms. The plasma membrane potential of rat cerebellar granule cells (CGC) in cerebellar slices or in primary cultures was measured using whole-cell current clamp recordings, or the fluorescent probe oxonol VI, respectively.

Glutamate, Glutamine and GABA Levels in Rat Brain Measured Using MRS, HPLC and NMR Methods in Study of Two Models of Autism.

The disorders of the glutamatergic neurotransmission have been associated with pathogenesis of autism. In this study we evaluated the impact of the and test methodology on measurements of levels of neurotransmitter amino acids in hippocampus of rats for valproic acid- (VPA) and thalidomide- (THAL) induced models of autism. The main goal was to compare the changes in concentrations of glutamate (Glu), glutamine (Gln) and GABA between both autistic groups and the control, measured and in homogenates.

Serum lipidomics in diagnostics of sarcoidosis.

The aim of this study was to determine the use of the lipid profile of patients with sarcoidosis and compare it with healthy subjects. We assume that lipid profile of serum in sarcoidosis differs from the lipid profile of control subjects. Serum was collected from 14 patients with II stage of sarcoidosis and 14 control subjects (healthy volunteers).

Altered expression of genes involved in programmed cell death in primary cultured rat cerebellar granule cells acutely challenged with tetrabromobisphenol A.

In the present study, primary cultures of rat cerebellar granule cells (CGC) and the RT Profiler PCR array were used to examine the effect of acutely applied brominated flame retardant tetrabromobisphenol A (TBBPA) on the expression of 84 genes related to the main modes of programmed cell death. CGC, at the 7th day of culture, were exposed to 10 or 25μM TBBPA for 30min. Then, 3, 6, and 24h later, the viability of the cells was examined by the staining with propidium iodide (PI) or using the calcein/ethidium homodimer (CA/ET) live/dead kit, and RNA was extracted for the evaluation of gene expression by RT-PCR.

Tetrabromobisphenol A disturbs zinc homeostasis in cultured cerebellar granule cells: A dual role in neurotoxicity.

The brominated flame retardant tetrabromobisphenol A (TBBPA) has recognized neurotoxic properties mediated by intracellular Ca imbalance and oxidative stress. Although these factors are known to trigger the release of Zn from intracellular stores, the effects of TBBPA on Zn homeostasis in neurons and the role of Znin TBBPA neurotoxicity have not yet been studied. Therefore, we investigated zinc transients in primary cultures of rat cerebellar granule cells and assessed their involvement in TBBPA neurotoxicity.

Select putative neurodevelopmental toxins modify SNAP-25 expression in primary cultures of rat cerebellar granule cells.

A presynaptic protein SNAP-25 belonging to SNARE complex which is instrumental in intracellular vesicular trafficking and exocytosis, has been implicated in hyperactivity and cognitive abilities in some neuropsychiatric disorders. The unclear etiology of the behavior disrupting neurodevelopmental disabilities in addition to genetic causes most likely involves environmental factors. The aim of this in vitro study was to test if various suspected developmental neurotoxins can alter SNAP-25 mRNA and protein expression in neurons.

The Role of Ca Imbalance in the Induction of Acute Oxidative Stress and Cytotoxicity in Cultured Rat Cerebellar Granule Cells Challenged with Tetrabromobisphenol A.

Using primary cultures of rat cerebellar granule cells (CGC) we examined the role of calcium transients induced by tetrabromobisphenol A (TBBPA) in triggering oxidative stress and cytotoxicity. CGC were exposed for 30 min to 10 or 25 µM TBBPA. Changes in intracellular calcium concentration ([Ca]), in the production of reactive oxygen species (ROS), and in the potential of mitochondria (∆Ψm) were measured fluorometrically during the exposure.

Zinc Modulates Nanosilver-Induced Toxicity in Primary Neuronal Cultures.

Silver nanoparticles (NAg) have recently become one of the most commonly used nanomaterials. Since the ability of nanosilver to enter the brain has been confirmed, there has been a need to investigate mechanisms of its neurotoxicity. We previously showed that primary neuronal cultures treated with nanosilver undergo destabilization of calcium homeostasis via a mechanism involving glutamatergic NMDA receptors.

Induction of inducible nitric oxide synthase expression in ammonia-exposed cultured astrocytes is coupled to increased arginine transport by upregulated y(+)LAT2 transporter.

One of the aspects of ammonia toxicity to brain cells is increased production of nitric oxide (NO) by NO synthases (NOSs). Previously we showed that ammonia increases arginine (Arg) uptake in cultured rat cortical astrocytes specifically via y(+)L amino acid transport system, by activation of its member, a heteromeric y(+)LAT2 transporter. Here, we tested the hypothesis that up-regulation of y(+)LAT2 underlies ammonia-dependent increase of NO production via inducible NOS (iNOS) induction, and protein nitration.

Role of Ryanodine and NMDA Receptors in Tetrabromobisphenol A-Induced Calcium Imbalance and Cytotoxicity in Primary Cultures of Rat Cerebellar Granule Cells.

The study assessed the role of ryanodine receptors (RyRs) and NMDA receptors (NMDARs) in the Ca(2+) transients and cytotoxicity induced in neurons by the brominated flame retardant tetrabromobisphenol A (TBBPA). Primary cultures of rat cerebellar granule cells (CGC) were exposed to 7.5, 10, or 25 µM TBBPA for 30 min, and cell viability was assessed after 24 h.

Bastadin 12 and ryanodine reveal similarities between thapsigargin- and tetrabromobisphenol A-induced intracellular Ca(2+) release in cultured cerebellar granule cells.

Tetrabromobisphenol A (TBBPA) is a commonly used brominated flame retardant with recognized neuro- and cytotoxic properties that are presumably mediated by intracellular Ca(2+) release. Other studies have demonstrated that ryanodine is able to inhibit Ca(2+) efflux from skeletal sarcoplasmic reticulum (SR) membranes in response to the known Ca(2+) releaser thapsigargin, provided that the macrocyclic brominated tyrosine derivative bastadin 5 is also present. Similar effects supporting the role of ryanodine receptors in thapsigargin-evoked Ca(2+) release have been observed in primary cultures of rat cerebellar granule cells (CGCs).