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l-glutamate (Glu) is the main excitatory neurotransmitter in the central nervous system (CNS) and is associated with motor behavior and sensory perception. While microdialysis methods have been used to record tonic levels of Glu, little is known about the more rapid changes in Glu signals that may be observed in awake rats. We have reported acute recording methods using enzyme-based microelectrode arrays (MEA) with fast response time and low detection levels of Glu in anesthetized animals with minimal interference. The current paper concerns modification of the MEA design to allow for reliable measures in the brain of conscious rats. In this study, we characterized the effects of chronic implantation of the MEA into the brains of rats. We were capable of measuring Glu levels for 7 days without loss of sensitivity. We performed studies of tail-pinch induced stress, which caused a robust biphasic increase in Glu. Histological data show chronic implantation of the MEAs caused minimal injury to the CNS. Taken together, our data show that chronic recordings of tonic and phasic Glu can be carried out in awake rats for up to 17 days in vivo allowing longer term studies of Glu regulation in behaving rats. [ABSTRACT FROM AUTHOR]

The article presents information about the "Journal of Neurochemistry" including the members of the editorial team, copyright and photocopying, and summaries of papers in the May 2016 issue.

This Preface introduces the articles of the special issue on 'Proteomics' where we survey these powerful techniques specifically in the context of applications in neurosciences. Proteomics as used here is a catch‐all term for approaches where a broad survey of all protein content of a cell or tissue is performed in parallel. In the special issue, various experts outline applications as diverse as finding disease biomarkers in human samples, including living participants or post‐mortem brain, as well as application of protein technologies to model systems such as animals and cells. Collectively, these articles outline the utility of current technologies for proteome interrogation and identify enhancements that will shape applications to future studies. This is the Preface for the special issue "Proteomics". Cover Image for this issue: doi: 10.1111/jnc.14530. [ABSTRACT FROM AUTHOR]

The article presents an abstract of the medical research paper "Interaction of Guanine Nucleotides With Glutamate Receptors: Possible Use as Neuroprotecting Agents." This paper is to be discussed in the Seventeenth Biennial Meeting of the International Society for Neurochemistry (ISN) and the Thirteenth General Meeting of the European Society for Neurochemistry (ESN) to be held at Berlin, Germany from August 8-14, 1999.

The article presents an abstract of the medical research paper "In Vivo and In Vitro Effects of Oxidative Stress on the Activity of Brain Nitric Oxide Synthase." This paper is to be discussed in the Seventeenth Biennial Meeting of the International Society for Neurochemistry (ISN) and the Thirteenth General Meeting of the European Society for Neurochemistry (ESN) to be held at Berlin, Germany from August 8-14, 1999.

The article presents an abstract of the medical research paper "Mechanism of Ruthenium Red Neurotoxicity." This paper is to be discussed in the Seventeenth Biennial Meeting of the International Society for Neurochemistry (ISN) and the Thirteenth General Meeting of the European Society for Neurochemistry (ESN) to be held at Berlin, Germany from August 8-14, 1999. This paper indicates that alterations of intracellular homeostasis may be responsible for the damaging effect of Ruthenium Red.

The article presents an abstract of the paper "Study of Glutamatergic Transmission and Neuronal Diversity by Single Cell RT-PCR." The paper will be presented at a joint meeting of the International Society for Neurochemistry and the European Society for Neurochemistry which will be organized in Berlin, Germany, from August 8-14, 1999. The kinetic properties of native AMPA receptors are probably controlled by multiple molecular determinants.

The article presents information on an abstract of the paper "Oxidative Stress Mediated Neurodegeneration and Down Sydrome," which will be presented at the 30th meeting of the American Society for Neurochemistry from March 14-17, 1999 in New Orleans, Louisiana. The paper states that long term overexpression of copper and Zinc superoxide dismutase creates an indigenous oxidative stress.

The article presents information on an abstract of the paper "Mechanismas of PDGF Enhanced Remyelination In Vivo," which will be presented at the 30th meeting of the American Society for Neurochemistry. The meeting will be held from March 14-17, 1999 in New Orleans, Louisiana. The paper findings highlight that PDGF accelerates the rate of remyelination after lysophosphatidylcholine injection in the corpus callosum of adults rats.

The article provides information on an abstract of the paper "Analysis of Migration and Differentiation of Mouse Hindbrain Oligodendrocyte Progenitor Cells in Flat Culture System," which will be presented at the 30th meeting of the American Society for Neurochemistry from March 14-17, 1999 in Louisiana. The paper findings highlight that oligodendrocytes are the myelinating cells in the central nervous system of a human body.

The article presents an abstract of a paper titled "Ouabain and an Endogenous Na+, K+-ATPase Inhibitor Modulate [3H]MK-801 Binding to NMDA Receptor," which will be presented at the 30th meeting of the American Society for Neurochemistry. The meeting will be held in New Orleans, Louisiana, from March 14 to 17, 1999. The paper suggests that methyl aspartate receptor can be modulated by ouabain and endobain E independent of modification of ionic gradient.

The article offers information on an abstract of the paper "Adults Human Oligodendrocytes Express Neuregulins and Erb-B Receptors," which will be presented at the 30th meeting of the American Society for Neurochemistry from March 14-17, 1999 in Louisiana. According to the paper, adults human oligodendrocytes proliferate but do not myelinate the margins of plaques with extensive myelin loss in multiple sclerosis.

The article presents an abstract of a paper titled "Elevated Phenylalanine Inhibits HMG-CoA" which will be presented at the 30th meeting of the American Society for Neurochemistry. The meeting will be held in New Orleans, Louisiana, from March 14 to 17, 1999. The paper suggests that the formation of the myelin sheath depends a lot on cholesterol.

The article presents an abstract of a paper titled "Is Asymetric Gap-43 Decreased Phosphorylation After Circling Training Related to Long Term Changes in mAch Receptor?," which will be presented at the 30th meeting of the American Society for Neurochemistry. The meeting will be held in New Orleans, Louisiana, from March 14 to 17, 1999. The paper supports that neuroplasticity markers, soon after postnatal running are linked to major changes in the receptor expression of striatum of an adult.

The article presents an abstract of a paper titled "Role of Helix-Loop-Helix Transcription Factors in Oligodendrocyte Differentiation and Myelination," which will be presented at the 30th meeting of the American Society for Neurochemistry. The meeting will be held in New Orleans, Louisiana, from March 14 to 17, 1999. The paper suggests that Oligodendrocytes, are negatively regulated by some inhibitors of differentiation (Id). Therefore, Ids are negative regulators of mylelination also.

The article presents an abstract of a paper titled "Ferritin and Transferrin Receptors Have Non-Overlapping Distributions in the Brain," which will be presented at the 30th meeting of the American Society for Neurochemistry. The meeting will be held in New Orleans, Louisiana, from March 14 to 17, 1999. The paper testifies that ferritin is present only in oligodendrocytes in the brain and is an important protein for iron delivery.

The article presents an abstract of a paper titled "Opioid-Induced Locomotion After Dopamine Depletion in the Nucleus Accumbens is Inhibited by Blocking Transmission in the Subthalamus," which will be presented at the 30th meeting of the American Society for Neurochemistry. The meeting will be held in New Orleans, Louisiana, from March 14 to 17, 1999. The paper focuses on Dopamine depletion in the nucleus accumbens that produces alterations in the motivational network circuitry.

The article presents an abstract of the paper "Hypothalamic Polypeftides- A New Family of Immuno-Modulators," which will be presented at the 30th Annual Meeting of the American Society for Neurochemistry to be held from March 14-17, 1999 in New Orleans, Louisiana. The paper suggests that hypothalamic polypeftides does contain certain properties which are similar to the ones present in immunomodulators and are found to be effective, to be used as drugs for clinical purposes.

The article presents the abstract of the paper "Mechanisms of Arachidonic Acid-Mediated Secondary Injury to Cultured Spinal Cord Neurons," which will be presented at the 30th meeting of the American Society for Neurochemistry. The meeting will be held in New Orleans, Louisiana, from March 14-17, 1999. According to the paper, secondary tissue injury and dysfunction of spinal cord neurons are greatly affected by the release of fatty acids during spinal cord trauma.

The article discusses an abstract of the paper "Identification of C/S-Elements in the 5' Flanking DNA that Mediate Glucocorticoid-Induced Augmentation of Tyrosine Hydroxylase Gene Expression." The paper will be presented at the 30th meeting of the American Society for Neurochemistry which will be held in New Orleans, Louisiana, from March 14-17, 1999. The study investigates the mechanism of glucocorticoids which amplify tyrosine hydroxylase gene transcription.

The article presents an abstract of the paper "Lipid Peroxidation and Oxidative Stress may Mediate Axonal Damage in Some Patients with Guillain Barre Syndrome and CIDP." The paper will be presented at the 30th meeting of the American Society for Neurochemistry which is scheduled to be held from March 14-17, 1999 in New Orleans, Louisiana. The paper concludes that oxidative stress does not decrease reduced glutathione levels.

The article presents an abstract of the paper "Permanent Rescue of Lesioned Motoneurons by Adenovirus-Mediated Expression of GDNF." The paper will be presented at the 30th meeting of the American Society for Neurochemistry which will be held from March 14-17, 1999 in New Orleans, Louisiana. According to the paper, transduction of neonatal motoneurons by retrograde transport of an adenoviral vector delays axotomy-induced death.

The article presents an abstract of the paper "Absolute Values for TCA Cycle Flux and Exchange of Glutamate, Glutamine, and GABA Between Neuronal and Glial Compartments of Adult Rat Brain During (1,2-13C2) Acetate Metabolism." The paper will be presented at the 30th meeting of the American Society for Neurochemistry. The meeting is scheduled to be held in New Orleans, Louisiana, from March 14-17, 1999. The paper describes the calculation of absolute values for glial tricarboxilic acid cycle.

The article discusses an abstract of a paper titled "Ecdysone-Inductible Expression of the Human Excitatory Amino Acid Transporter 2 (Eaat 2) in HEK 293 cells." The paper will be discussed at the 30th meeting of the American Society for Neurochemistry which is scheduled to be held in New Orleans, Louisiana, from March 14-17 1999. The majority of the L-glutamate transport activity present in adult forebrain is the outcome of high-affinity L-glutamate transporter EAAT2/GLT-1.

One of the aims of basic neuroscience research is ultimately the development of therapeutics to cure diseases. Funders granting money to research institutions increasingly express interest into how their financial resources are used and look for successful translation in clinical practice. Disappointingly, many findings that started out promising in basic research projects and phase I trials did not live up to the promise of therapeutic efficacy in later phase II or III trials. An inordinately high amount of time and money is thus spent on research that does not always have the required human impact. Potential reasons for these problems are numerous. Although research misconduct occurs and contributes to this shortcoming, it is not the only important factor. Frequently, basic science results turn out to be irreproducible. Irreproducibility, outside of malfeasance, is multifactorial and can include poor experimental design, conduct, statistical analysis, reporting standards, and conceptual flaws. Further confounding problems include an insufficient transferability of animal to human physiology, as well as intersubject group variability, for example, sexual dimorphisms. While the causes of poor data reproducibility are therefore numerous, equally there are many groups that can contribute to improvements in how basic science is reported. Here, we will review how the Journal of Neurochemistry can contribute to increasing the value of preclinical and translational research. [ABSTRACT FROM AUTHOR]

The article presents abstracts on neurosciences which include developments in neurochemistry before the International Society for Neurochemistry (ISN), glycogen synthase kinase 3b's (GSK-3b) role in neurodegeneration due to Alzheimer and oligodendrocyte progenitor cells (OPCs) in remyelination.

The article presents abstracts on neurosciences which include epigenetic involved in neural stem cells' maintenance, neuroregenerative and neuroprotective treatment for ischemic stroke and human embryonic stem cell-derived cortical progenitor transplantation supported by bioengineered scaffold.

The article presents abstracts on neurosciences which include cause of impaired myelination in intrauterine growth restricted (IUGR) rats, glia cell activation by anticoagulant warfarin and lipid peroxidation of mylein structure of nerve limited by calcium channels inhibitors.

The article presents abstracts on neurosciences which include spinal astrocyte expression alteration in 5-fluorouracil induced intestinal mucositis, single cell approach in gene expression profiling of astrocytes and glutamate transporters regulation by methylphenidate in bergmann glial cells.

The article presents abstracts related to neurochemistry including "Neurochemistry and tissue culture: Founding fathers and cardinal contributions," by G. H. DeVries, "Coining the basic terms of neurochemistry," by A. I. Boullerne, and "Neurochemistry studied with the microchemical methods of Oliver H. Lowry," by D. A. Godfrey.

The article presents abstracts on neurochemistry which include analysis of the influence of the antioxidant carnosine on the clinicobiological characteristics of alcoholic patients during rehabilitation, metabolic control analysis of bioenergetic function in synaptosomes, and effects of tolbutamide in rat and human glioma cell proliferation.

Alterations in astrocyte function that may affect neuronal viability occur with brain aging. In this study, we evaluate the neuroprotective capacity of astrocytes in an experimental model of in vitro aging. Changes in oxidative stress, glutamate uptake and protein expression were evaluated in rat cortical astrocytes cultured for 10 and 90 days in vitro (DIV). Levels of glial fibrillary acidic protein and S100β increased at 90 days when cells were positive for the senescence β-galactosidase marker. In long-term astrocyte cultures, the generation of reactive oxygen species was enhanced and mitochondrial activity decreased. Simultaneously, there was an increase in proteins that stained positively for nitrotyrosine. The expression of Cu/Zn-superoxide dismutase (SOD-1) and haeme oxygenase-1 (HO-1) proteins and inducible nitric oxide synthase (iNOS) increased in aged astrocytes. Glutamate uptake in 90-DIV astrocytes was higher than in 10 DIV ones, and was more vulnerable to inhibition by H2O2 exposure. Enhanced glutamate uptake was probably because of up-regulation of the glutamate/aspartate transporter protein. Aged astrocytes had a reduced ability to maintain neuronal survival. These findings indicate that astrocytes may partially loose their neuroprotective ability during aging. The results also suggest that aged astrocytes may contribute to exacerbating neuronal injury in age-related neurodegenerative processes. [ABSTRACT FROM AUTHOR]

Mutations in the gene encoding the purine salvage enzyme, hypoxanthine–guanine phosphoribosyltransferase (HPRT) cause Lesch-Nyhan disease, a neurodevelopmental disorder characterized by cognitive, neurological, and behavioral abnormalities. Despite detailed knowledge of the enzyme’s function, the key pathophysiological changes that accompany loss of purine recycling are unclear. To facilitate delineating the consequences of HPRT deficiency, four independent HPRT-deficient sublines of the human dopaminergic neuroblastoma, SK-N-BE(2) M17, were isolated by targeted mutagenesis with triple helix-forming oligonucleotides. As a group, these HPRT-deficient cells showed several significant abnormalities: (i) impaired purine recycling with accumulation of hypoxanthine, guanine, and xanthine, (ii) reduced guanylate energy charge and GTP : GDP ratio, but normal adenylate energy charge and no changes in any adenine nucleotide ratios, (iii) increased levels of UTP and NADP+, (iv) reduced DOPA decarboxylase, but normal monoamines, and (v) reduction in cell soma size. These cells combine the analytical power of multiple lines and a human, neuronal origin to provide an important tool to investigate the pathophysiology of HPRT deficiency. [ABSTRACT FROM AUTHOR]

CCAAT/enhancer binding protein β (C/EBPβ) is a leucine-zipper transcription factor that regulates cell growth and differentiation in mammals. Expression of many pro-inflammatory genes including the cytokine interleukin-6 is known to be controlled by C/EBPβ. We report that focal cerebral ischemia induced by transient middle cerebral artery occlusion (MCAO) significantly increases C/EBPβ gene expression in mouse brain at between 6 and 72 h of reperfusion. To understand the functional significance of C/EBPβ in postischemic inflammation and brain damage, we induced transient MCAO in cohorts of adult C/EBPβ null mice and their wild-type littermates. At 3 days of reperfusion following transient MCAO, C/EBPβ null mice showed significantly smaller infarcts, reduced neurological deficits, decreased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells, decreased intercellular adhesion molecule 1 (ICAM1) immunopositive vessels, decreased extravasated neutrophils and fewer activated microglia/macrophages, compared with their wild-type littermates. Furthermore, GeneChip analysis showed that postischemic induction of many transcripts known to promote inflammation and neuronal damage was less pronounced in the brains of C/EBPβ–/– mice compared with C/EBPβ+/+ mice. These results suggest a significant role for C/EBPβ in postischemic inflammation and brain damage. [ABSTRACT FROM AUTHOR]

The article presents abstracts of papers related to neuronal connexins, which were presented at a workshop at the joint meeting of the International Society for Neurochemistry and the American Society for Neurochemistry, in Buenos Aires, Argentina from August 26-31, 2001. They include "Expression patters of neuronal gap junction proteins in mammalian brain," and "Cell-cell communication in the eye: clarifying the need for connexin diversity."

Although microdialysis measurements suggest that extracellular dopamine concentrations in the rat striatum are in the low nanomolar range, some recent voltammetry studies suggest that the concentration may be considerably higher, perhaps in the micromolar range. The presence of such high dopamine levels in the extracellular space has to be rationalized with the rapid, linear clearance of extracellular dopamine observed after electrical stimulation of the medial forebrain bundle. Kinetic analysis of dopamine clearance after evoked release suggests that the basal extracellular dopamine concentration is below the KM of dopamine uptake, which is near 0.2 µ m. However, dopamine clearance after pressure ejection of dopamine into the rat striatum is slow and non-linear, which may alternatively be a sign that basal dopamine release is only slightly slower than the maximal velocity of dopamine uptake, Vmax. A high basal extracellular dopamine concentration would exist if basal dopamine release were only slightly slower than the Vmax of uptake. This report introduces a new kinetic analysis of dopamine uptake that sheds light on the possible source of the different clearance rates observed following evoked dopamine release and dopamine pressure ejection. Furthermore, the analysis rationalizes the rapid dopamine clearance after evoked release with the possibility that basal extracellular dopamine levels are above the KM of the transporter. [ABSTRACT FROM AUTHOR]

Reperfusion after global brain ischemia results initially in a widespread suppression of protein synthesis in neurons that is due to inhibition of translation initiation as a result of the phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2). To address the role of the eIF2α kinase RNA-dependent protein kinase-like endoplasmic reticulum kinase (PERK) in the reperfused brain, transgenic mice with a targeted disruption of the Perk gene were subjected to 20 min of forebrain ischemia followed by 10 min of reperfusion. In wild-type mice, phosphorylated eIF2α was detected in the non-ischemic brain and its levels were elevated threefold after 10 min of reperfusion. Conversely, there was no phosphorylated eIF2α detected in the non-ischemic transgenic mice and there was no sizeable rise in phosphorylated eIF2α levels in the forebrain after ischemia and reperfusion. Moreover, there was a substantial rescue of protein translation in the reperfused transgenic mice. Neither group showed any change in total eIF2α, phosphorylated eukaryotic elongation factor 2 or total eukaryotic elongation factor 2 levels. These data demonstrate that PERK is responsible for the large increase in phosphorylated eIF2α and the suppression of translation early in reperfusion after transient global brain ischemia. [ABSTRACT FROM AUTHOR]

It is well known that tau is a good in vitro substrate for Ca2+/calmodulin-dependent protein kinase II (CaM kinase II). However, it is not clear at present whether CaM kinase II phosphorylates tau in vivo or not. Serine 416, numbered according to the longest human tau isoform, has been reported to be one of the major phosphorylation sites by CaM kinase II in vitro. In this study, we produced a specific antibody against tau phosphorylated at serine 416 (PS416-tau). Immunoblot analysis revealed that the antibody reacted with tau in the rat brain extract which was prepared in the presence of protein phosphatase inhibitors. Developmental study indicated that serine 416 was strongly phosphorylated at early developmental stages in rat brain. We examined the localization of PS416-tau in primary cultured hippocampal neurons and the immortalized GnRH neurons (GT1-7 cells), which were stably transfected with CaM kinase IIα cDNA. Immunostaining of these cells indicated that tau was phosphorylated mainly in neuronal soma. Interestingly, tau in neuronal soma in Alzheimer's disease (AD) brain was strongly immunostained by the antibody. These results suggest that CaM kinase II is involved in the accumulation of tau in neuronal soma in AD brain. [ABSTRACT FROM AUTHOR]

Large-conductance Ca2+-activated K+ (BKCa) channels are activated by membrane depolarization and modulated by intracellular Ca2+. Here, we report the direct interaction of cereblon (CRBN) with the cytosolic carboxy-terminus of the BKCa channel α subunit (Slo). Rat CRBN contained the N-terminal domain of the Lon protease, a ‘regulators of G protein-signaling’ (RGS)-like domain, a leucine zipper (LZ) motif, and four putative protein kinase C (PKC) phosphorylation sites. RNA messages of rat cereblon (rCRBN) were widely distributed in different tissues with especially high-levels of expression in the brain. Direct association of rCRBN with the BKCa channel was confirmed by immunoprecipitation in brain lysate, and the two proteins were co-localized in cultured rat hippocampal neurons. Ionic currents evoked by the rSlo channel were dramatically suppressed upon coexpression of rCRBN. rCRBN decreased the formation of the tetrameric rSlo complex thus reducing the surface expression of functional channels. Therefore, we suggest that CRBN may play an important role in assembly and surface expression of functional BKCa channels by direct interaction with the cytosolic C-terminus of its α-subunit. [ABSTRACT FROM AUTHOR]

Ginkgo bilobaextract (EGb), a potent antioxidant and monoamine oxidase B (MAO-B) inhibitor, was evaluated for its anti-parkinsonian effects in a 6-hydroxydopamine (6-OHDA) rat model of the disease. Rats were treated with 50, 100, and 150 mg/kg EGb for 3 weeks. On day 21, 2 µL 6-OHDA (10 µg in 0.1% ascorbic acid saline) was injected into the right striatum, while the sham-operated group received 2 µL of vehicle. Three weeks after 6-OHDA injection, rats were tested for rotational behaviour, locomotor activity, and muscular coordination. After 6 weeks, they were killed to estimate the generation of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content, to measure activities of glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD), and to quantify catecholamines, dopamine (DA) D2 receptor binding, and tyrosine hydroxylase-immunoreactive (TH-IR) fibre density. The increase in drug-induced rotations and deficits in locomotor activity and muscular coordination due to 6-OHDA injections were significantly and dose-dependently restored by EGb. The lesion was followed by an increased generation of TBARS and significant depletion of GSH content in substantia nigra, which was gradually restored with EGb treatment. EGb also dose-dependently restored the activities of glutathione-dependent enzymes, catalase, and SOD in striatum, which had reduced significantly by lesioning. A significant decrease in the level of DA and its metabolites and an increase in the number of dopaminergic D2 receptors in striatum were observed after 6-OHDA injection, both of which were significantly recovered following EGb treatment. Finally, all of these results were exhibited by an increase in the density of TH-IR fibers in the ipsilateral substantia nigra of the lesioned group following treatment with EGb; the lesioning had induced almost a complete loss of TH-IR fibers. Considering our behavioural studies, biochemical analysis, and immunohistochemical observation, we conclude that EGb can be used as a therapeutic approach to check the neuronal loss following parkinsonism. [ABSTRACT FROM AUTHOR]

Intracerebral microdialysis is a popular technique for studying neurochemistry and neural circuits in various brain regions. Recent studies called into question the validity of the microdialysis zero-net-flux (ZNF) method by suggesting that this method significantly underestimates the basal level of extracellular dopamine as a result of the discreteness of dopamine release sites as well as the preferential damage to dopamine release over uptake. To identify which factor is most important in undermining the microdialysis ZNF measurements and the extent of underestimation, two mathematical models were developed to explore the influences of the discrete nature and the probe-induced impairment in the neurotransmitter release. The two models differ in their characterizations of the transmitter release as spatially discrete and homogeneous, respectively. Simulations using physiologically reasonable parameters for striatal dopamine systems indicate that the preferential release site damage surrounding the implanted probe is the most important determinant to the underestimation of the microdialysis ZNF concentration. Under normal physiological conditions, the discreteness of neurotransmitter release sites is of minor importance, except when neuronal degeneration occurs. It is concluded that homogeneous models can adequately describe microdialysis operating processes as long as the corresponding tissue damage parameters in such models are appropriately incorporated. [ABSTRACT FROM AUTHOR]

Degeneration of dopaminergic neurons in the substantia nigra is associated with one of the most prominent human neurological disorders, Parkinson's disease. It is therefore of high interest to identify molecules with trophic effects on this neuronal population. We show here that the neuregulin receptorErbB4is differentially expressed in mesencephalic dopaminergic neurons, found in the substantia nigra and in a subregion of the ventral tegmentum but not in the retrorubral field. Early developmental onset and continued expression ofErbB4into the adult and the presence of two high affinity ligands,neuregulin-1andbetacellulin, in the basal ganglia, suggested that these molecules might participate in the differentiation and/or maintenance of the nigrostriatal system. In order to address this hypothesis,we used a loxP flankedErbB4allele in combination with a nestin-Cre transgene and generated brain-specificErbB4null mice. These mutant animals survived into adulthood. The distribution of dopaminergic cell bodies in the midbrain, the expression of numerous genes specific to mesencephalic dopaminergic neurons, and the axonal projection to the basal ganglia all appeared normal. Finally, an assessment of their motor function revealed no behavioral deficits. The apparent lack of any mutant phenotype suggests the presence of a strong compensatory mechanism. [ABSTRACT FROM AUTHOR]

Opioid receptors are expressed in neuronal and immune cells and regulated in response to immunological processes. Herein, we demonstrate up-regulation of theδ-opioid receptor gene by interleukin-4 in immune cells (primary T and polymorphonuclear leukocytes, Jurkat E6 T cells), and in NG 108–15 neuronal cells. We identified an interleukin-4-responsive element at nt−671 on the murine gene promoter, to which the transcription factor STAT6 binds, as shown by reporter gene analysis and STAT6/DNA interaction studies in living cells with transcription factor decoy oligonucleotides. STAT6 normally binds to palindromic DNA motifs with a 5′-TTC...GAA-3′ core. Notably, theδ-opioid receptor STAT6 site (5′-TTC...GA-3′) is an imperfect palindrome with a mismatch within this core sequence. A systematic analysis of possible mismatch 5′-TTC...GAA-3′ motifs revealed that STAT6 also binds to the sequence 5′-TT...GAA-3′. This motif occurs as a polymorphism in the humanµ-opioid receptor gene (J. Biol. Chem 276, 43901–43908). We show that this mutated element has a significantly reduced STAT6 binding activity which correlates to its reduced interleukin (IL)-4 inducibility. In contrast, the non-canonical STAT6 site of theδ-opioid receptor binds STAT6 with similar high activity as a perfectly palindromic STAT6 site and is strongly inducible by IL-4. [ABSTRACT FROM AUTHOR]

The article presents an abstract of the research paper "L-Glutamic Acid - Endogenic Differentiation Factor of HL-60 Cells." The research shows that L-Glutamic acid (L-Glu) is known to be the important neuromediator in the central nervous system and is acting through different types of glutamate receptors. The research finds that L-Glu decreased the expression level of mRNA of IL-1 and IL-6, and increased the expression of mRNA of TNF-a.

The article presents an abstract of the research paper "Neuroblastoma Cell Differentiation and Upregulation of Nuclear GM1." It will be presented in the joint meeting of the International Society for Neurochemistry and the European Society of Neurochemistry that will be held in Berlin, Germany from August 8-14, 1999. The study findings highlight that Neuro-2a formed a significant number of axon-like neurites and showed upregulation of nuclear GM1.

The article presents an abstract of the research paper "Effects of Ammonia on Glutamate (glt-1 and glast) Transporter Expression in Cultured Astrocytes." It concludes that pathogenesis of central nervous system dysfunction in hyperammonemic disorders such as urea cycle enzymopathies and HE may act as factor in increasing extracellular concentrations of glutamate.

The article presents an abstract of the research paper "Effect of Depolarization on cAMP Level in Rat Brain Synaptosomes." It discusses the connection between calcium ions and cAMP dependent pathways on postsynaptic level of intracellular signalling involves in synaptic plasticity and memory engramms formation.