bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arachidonic acid and docosahexaenoic acid suppress thrombin‐evoked Ca2+ response in rat astrocytes by endogenous arachidonic acid liberation
Authors: Sergeeva Marina , Strokin Mikhail , Wang Hong , Ubl Joachim J. , Reiser Georg 
Published: March 2003

AbstractArachidonic (AA) and docosahexaenoic acid (DHA) are the major polyunsaturated fatty acids (PUFAs) in the brain. However, their influence on intracellular Ca2+ signalling is still widely unknown. In astrocytes, the amplitude of thrombin‐ induced Ca2+ response was time‐dependently diminished by AA and DHA, or by the AA tetraynoic analogue ETYA, but not by eicosapentaenoic acid (EPA). Thrombin‐elicited Ca2+ response was reduced (20–30%) by 1‐min exposure to AA or DHA. Additionally, 1‐min application of AA or DHA together with thrombin in Ca2+‐free medium blocked Ca2+ influx, which followed after readdition of extracellular Ca2+. EPA and ETYA, however, were ineffective. Long‐term treatment of astrocytes with AA and DHA, but not EPA reduced the amplitude of the thrombin‐induced Ca2+ response by up to 80%. AA and DHA caused a comparable decrease in intracellular Ca2+ store content. Only DHA and AA, but not EPA or ETYA, caused liberation of endogenous AA by cytosolic phospholipase A2 (cPLA2). Therefore, we reasoned that the suppression of Ca2+ response to thrombin by AA and DHA could be due to release of endogenous AA. Possible participation of AA metabolites, however, was excluded by the finding that specific inhibitors of the different oxidative metabolic pathways of AA were not able to abrogate the inhibitory AA effect. In addition, thrombin evoked AA release via activation of cPLA2. From our data we propose a novel model of positive/negative‐feed‐back in which agonist‐induced release of AA from membrane phospholipids promotes further AA release and then suppresses agonist‐induced Ca2+ responses.
Mixed lineage kinase 3 mediates gp120IIIB‐induced neurotoxicity
Authors: Bodner Amos , Maroney Anna C. , Finn James P. , Ghadge Ghanashyam , Roos Raymond , Miller Richard J. 
Published: March 2003

AbstractOverexpression of gp120, the major coat protein of the HIV‐1 virus, in central glial cells, or treatment of neurons with gp120 in culture, produces apoptotic neuronal death. Here we demonstrate that CEP‐1347 (KT7515), an inhibitor of mixed lineage kinase 3 (MLK3), an upstream activator of JNK, inhibits gp120IIIB‐induced apoptosis of hippocampal neurons. Furthermore, expression of wild type MLK3 in hippocampal pyramidal neurons enhanced gp120IIIB‐induced neurotoxicity, whereas expression of a dominant negative MLK3 protected neurons from the toxic effects of the glycoprotein. These results indicate a role for MLK3 signaling in gp120IIIB‐induced neuronal death, and suggest potential clinical utility of CEP‐1347 in inhibiting the progression of AIDS dementia.
NMDA‐induced acetylcholine release in mouse striatum: role of NO synthase isoforms
Authors: Buchholzer Marie‐Luise , Klein Jochen 
Published: March 2003

AbstractStriatal cholinergic interneurons are stimulated by glutamatergic inputs from thalamus and cortex via NMDA receptors. The present microdialysis study was designed to characterize the role of nitric oxide (NO) in this process and to identify the NO synthase (NOS) isoform responsible for this effect. For this purpose, we studied the effects of NMDA and 3‐morpholino sydnonimine (SIN‐1) perfusions on the release of acetylcholine (ACh) in mouse striatum. In wild‐type C57/Bl6 mice, perfusion of NMDA (100 µm) induced a two‐fold stimulation of ACh release. This effect was attenuated in mice lacking endothelial NOS but was completely absent in mice lacking neuronal NOS. Local perfusion of SIN‐1 (300 µm), an NO donor, increased ACh release by more than two‐fold in all three mouse lines. We conclude that NO synthesized by neuronal NOS provides a nitrergic link in the glutamatergic stimulation of striatal cholinergic interneurons.
Phosphatidylinositol‐3 kinase p85 enhances expression from the myelin basic protein promoter in oligodendrocytes
Authors: E. Clark Robert , Miskimins W. Keith , Miskimins Robin 
Published: March 2003

AbstractPhosphatidylinositol‐3 kinase (PI3K) is a family of enzymes that phosphorylates the D3 position of phosphoinositides in membranes which can then act as a second messenger and affect many essential cellular processes such as survival, proliferation and differentiation. Class IA PI3K is composed of two subunits: a regulatory subunit, p85, and a catalytic subunit, p110. The p85 subunit is composed of several adapter domains which, upon interaction with the appropriate molecules, transmit the signal to activate p110. We have used the spontaneously immortalized oligodendrocyte cell line, CG4, to examine the role of PI3K in maturation of the oligodendrocyte. We show that overexpression of the p85 subunit enhances expression of myelin basic protein (MBP) upon differentiation of CG4 cells and primary oligodendrocytes. In experiments in CG4 cells, neither cotransfection with the tumor suppressor PTEN, which dephosphorylates the D3 position of phosphoinositides, nor inhibition of PI3K activity with wortmannin mimics this effect. Further, we have shown that this effect is dependent on the coexpression of the two SH2 domains within p85. Thus, the p85‐mediated enhancement of MBP promoter activity in oligodendrocytes appears to be independent of PI3K activity and dependent on the adapter functions of the p85 subunit's SH2 domains.
Glial uptake of neurotransmitter glutamate from the extracellular fluid studiedin vivoby microdialysis and13C NMR
Authors: Kanamori Keiko , Ross Brian D. , Kondrat Richard W. 
Published: March 2003

AbstractGlial uptake of neurotransmitter glutamate (GLU) from the extracellular fluid was studiedin vivoin rat brain by13C NMR and microdialysis combined with gas‐chromatography/mass‐spectrometry. Brain GLU C5 was13C enriched by intravenous [2,5‐13C]glucose infusion, followed by [12C]glucose infusion to chase13C from the small glial GLU pool. This leaves [5‐13C]GLU mainly in the large neuronal metabolic pool and the vesicular neurotransmitter pool. During the chase, the13C enrichment of whole‐brain GLU C5 was significantly lower than that of extracellular GLU (GLUECF) derived from exocytosis of vesicular GLU. Glial uptake of neurotransmitter [5‐13C]GLUECFwas monitoredin vivothrough the formation of [5‐13C,15N]GLN during15NH4Ac infusion. From the rate of [5‐13C,15N]GLN synthesis (1.7 ± 0.03 µmol/g/h), the mean13C enrichment of extracellular GLU (0.304 ± 0.011) and the15N enrichment of precursor NH3(0.87 ± 0.014), the rate of synthesis of GLN (V′GLN), derived from neurotransmitter GLUECF, was determined to be 6.4 ± 0.44 µmol/g/h. Comparison with VGLNmeasured previously by an independent method showed that the neurotransmitter provides 80–90% of the substrate GLU pool for GLN synthesis. Hence, under our experimental conditions, the rate of 6.4 ± 0.44 µmol/g/h also represents a reasonable estimate for the rate of glial uptake of GLUECF, a process that is crucial for protecting the brain from GLU excitotoxicity.
Human immunodeficiency virus‐1 Tat protein and methamphetamine interact synergistically to impair striatal dopaminergic function
Authors: Maragos William F. , Young Kristie L. , Turchan Jadwiga T. , Guseva Masha , Pauly James R. , Nath Avi , Cass Wayne A. 
Published: March 2003

AbstractThe human immunodeficiency virus (HIV)‐1 transactivating protein Tat may be pathogenically relevant in HIV‐1‐induced neuronal injury. The abuse of methamphetamine (MA), which is associated with behaviors that may transmit HIV‐1, may damage dopaminergic afferents to the striatum. Since Tat and MA share common mechanisms of injury, we examined whether co‐exposure to these toxins would lead to enhanced dopaminergic toxicity. Animals were treated with either saline, a threshold dose of MA, a threshold concentration of Tat injected directly into the striatum, or striatal injections of Tat followed by exposure to MA. Threshold was defined as the highest concentration of toxin that would not result in a significant loss of striatal dopamine levels. One week later, MA‐treated animals demonstrated a 7% decline in striatal dopamine levels while Tat‐treated animals showed an 8% reduction. Exposure to both MA + Tat caused an almost 65% reduction in striatal dopamine. This same treatment caused a 56% reduction in the binding capacity to the dopamine transporter. Using human fetal neurons, enhanced toxicity was also observed when cells were exposed to both Tat and MA. Mitochondrial membrane potential was disrupted and could be prevented by treatment with antioxidants. This study demonstrates that the HIV‐1 ‘virotoxin’ Tat enhances MA‐induced striatal damage and suggests that HIV‐1‐infected individuals who abuse MA may be at increased risk of basal ganglia dysfunction.
Identification of JNK‐dependent and ‐independent components of cerebellar granule neuron apoptosis
Authors: Harris Charles , Maroney Anna C. , Johnson Eugene M. 
Published: March 2003

AbstractCerebellar granule neurons grown in high potassium undergo rapid apoptosis when switched to medium containing 5 mm potassium, a stimulus mimicking deafferentation. This cell death can be blocked by genetic deletion of Bax, a member of the pro‐apoptotic Bcl‐2 family, cycloheximide an inhibitor of macromolecular synthesis or expression of dominant‐negative c‐jun. These observations suggest that Bax activation is the result of c‐jun target gene(s) up‐regulation following trophic withdrawal. Candidate genes include the BH3‐only Bcl‐2 family members Dp5 and Bim. The molecular mechanisms underlying granule cell neuronal apoptosis in response to low potassium were investigated using CEP‐1347 (KT7515), an inhibitor of the MLK family of JNKKK. CEP‐1347 provided protection of potassium–serum‐deprived granule cells, but such neuroprotection was not long term. The incomplete protection was not due to incomplete blockade of the JNK signaling pathway because c‐jun phosphorylation as well as induction of c‐jun RNA and protein were completely blocked by CEP‐1347. Following potassium–serum deprivation the JNKK MKK4 becomes phosphorylated, an event blocked by CEP‐1347. Cells that die in the presence of CEP‐1347 activate caspases; and dual inhibition of caspases and MLKs has additive, not synergistic, effects on survival. A lack of synergism was also seen with the p38 inhibitor SB203580, indicating that the neuroprotective effect of the JNK pathway inhibitor cannot be explained by p38 activation. Activation of the JNK signaling pathway seems to be a key event in granule cell apoptosis, but these neurons cannot survive long term in the absence of sustained PI3 kinase signaling.
A caspase‐3‐dependent pathway is predominantly activated by the excitotoxin pregnenolone sulfate and requires early and late cytochrome c release and cell‐specific caspase‐2 activation in the retinal cell death
Authors: Cascio C. , Guarneri R. , Russo D. , De Leo G. , Guarneri M. , Piccoli F. , Guarneri P. 
Published: March 2003

AbstractThis study investigates the implication of mitochondria‐ and caspase‐dependent pathways in the death of retinal neurones exposed to the neurosteroid pregnenolone sulfate (PS) shown to evoke apoptosis and contribute to amplification and propagation of excitotoxicity. After a brief PS challenge of intact retinas, caspase‐3 and caspase‐2 activation and cytochrome c release occur early and independent of changes in the oxidative state measured by superoxide dismutase activity. The temporal and spatial relationship of these events suggests that a caspase‐3‐dependent pathway is activated in response to cytochrome c release and requires caspase‐2 activation and a late cytochrome c release in specific cellular subsets of retinal layers. The protection by caspase inhibitors indicates a predominant role of the pathway in PS‐induced retinal apoptosis, although a limited use of caspase inhibitors is upheld on a conceivable shift from apoptosis toward necrosis. Conversely, 3α‐hydroxy‐5β‐pregnan‐20‐one sulfate and 17β‐oestradiol provide complete prevention of PS‐induced retinal death.
Impaired postnatal development of hippocampal neurons and axon projections in the Emx2–/– mutants
Authors: Savaskan Nicolai E. , Alvarez‐Bolado Gonzalo , Glumm Robert , Nitsch Robert , Skutella Thomas , Heimrich Bernd 
Published: March 2003

AbstractThe specification and innervation of cerebral subregions is a complex layer‐specific process, primed by region‐specific transcription factor expression and axonal guidance cues. In Emx2–/– mice, the hippocampus fails to form a normal dentate gyrus as well as the normal layering of principal neurons in the hippocampus proper. Here, we analyzed the late embryonic and postnatal development of the hippocampal formation and its axonal projections in mice lacking Emx2 expression in vitro. As these mutants die perinatally, we used slice cultures of Emx2 mutant hippocampus to circumvent this problem. In late embryonic Emx2–/– cultivated hippocampi, both the perforant path as well as the distribution of calretinin‐positive cells are affected. Traced entorhinal afferents in co‐cultures with hippocampus from embryonic Emx2–/– mice terminate diffusely in the prospective dentate gyrus in contrast to the layer‐specific termination of co‐cultures from wild‐type littermates. In addition, in brain slice cultures from null mutants the presumptive dentate gyrus failed to develop its normal cytoarchitecture and mature dentate granule cells, including the lack of their mossy fiber projection. Our data indicate that Emx2 is essential for the terminal differentiation of granular cells and the correct formation of extrinsic and intrinsic hippocampal connections.
Transient modulation of cytoplasmic and nuclear retinoid receptors expression in differentiating human teratocarcinoma NT2 cells
Authors: Borghi Roberta , Venè Roberta , Arena Giuseppe , Schubert David , Albini Adriana , Tosetti Francesca 
Published: March 2003

AbstractHuman embryonal carcinoma Ntera2/D1 (NT2) cells treated with retinoic acid (RA) differentiate into several cell types including post‐mitotic neurons. In this study we asked if RA‐induced differentiation alters the expression of RA and retinol (ROL) binding proteins. The regulation of the intracellular carrier proteins for ROL and RA, cellular retinol binding protein I (CRBP‐I), and cellular retinoic acid binding protein I and II (CRABP‐I, CRABP‐II) were studied along with the nuclear RA receptors RARα, RARβ and RARγ2. PCR analysis of total mRNA from RA‐treated cells showed a biphasic early induction of CRBP‐I, CRABP‐II, and RARγ2 genes. The immediate early gene Krox‐24, a zinc finger transcription factor which is up‐regulated during neuronal differentiation, was also induced, but after 1 week of treatment. The induction of CRBP‐I protein synthesis in differentiating NT2 cells was confirmed by western blotting and immunofluorescence experiments. Conversely, the synthetic retinoid N‐(4‐hydroxyphenyl)retinamide, which induces cell death, but not differentiation in different tumour cell types, did not produce the same modulation on gene expression in NT2 cells. These data suggest that the RA‐specific induction of CRBP‐I and CRABP‐II could be an early event in the process leading to neuronal differentiation of NT2 cells.
Differential regulation of somatodendritic and nerve terminal dopamine release by serotonergic innervation of substantia nigra
Authors: Cobb William S. , Abercrombie Elizabeth D. 
Published: March 2003

AbstractNigrostriatal dopaminergic neurons release dopamine from dendrites in substantia nigra and axon terminals in striatum. The cellular mechanisms for somatodendritic and axonal dopamine release are similar, but somatodendritic and nerve terminal dopamine release may not always occur in parallel. The current studies used in vivo microdialysis to simultaneously measure changes in dendritic and nerve terminal dopamine efflux in substantia nigra and ipsilateral striatum respectively, following intranigral application of various drugs by reverse dialysis through the nigral probe. The serotonin releasers (+/–)‐fenfluramine (100 µm) and (+)‐fenfluramine (100 µm) significantly increased dendritic dopamine efflux without affecting extracellular dopamine in striatum. The non‐selective serotonin receptor agonist 1‐(m‐chlorophenyl)‐piperazine (100 µm) elicited a similar pattern of dopamine release in substantia nigra and striatum. NMDA (33 µm) produced an increase in nigral dopamine of a similar magnitude to mCPP or either fenfluramine drug. However, NMDA also induced a concurrent increase in striatal dopamine. The D2 agonist quinpirole (100 µm) had a parallel inhibitory effect on dopamine release from dendritic and terminal sites as well. Taken together, these data suggest that serotonergic afferents to substantia nigra may evoke dendritic dopamine release through a mechanism that is uncoupled from the impulse‐dependent control of nerve terminal dopamine release.
Plasticity of glutamatergic control of striatal acetylcholine release in experimental parkinsonism: opposite changes at group‐II metabotropic and NMDA receptors
Authors: Marti Matteo , Paganini Francesca , Stocchi Sara , Mela Flora , Beani Lorenzo , Bianchi Clementina , Morari Michele 
Published: March 2003

AbstractTo investigate whether adaptive changes of glutamatergic transmission underlie dysfunction of the cholinergic system in experimental parkinsonism, the effects of group‐II metabotropic glutamate and NMDA receptor ligands on acetylcholine release was studied in striatal slices and synaptosomes obtained from naive rats, 6‐hydroxydopamine hemi‐lesioned rats and 6‐hydroxydopamine hemi‐lesioned rats chronically treated with levodopa (l‐DOPA) plus benserazide (non‐dyskinetic). Group‐II metabotropic glutamate receptor agonists LY354740, DCG‐IV and l‐CCG‐I inhibited the electrically‐evoked endogenous acetylcholine release from slices, while NMDA facilitated it. LY354740 also inhibited K+‐evoked acetylcholine release from synaptosomes. LY354740‐induced inhibition was prevented by the group‐II metabotropic glutamate receptor antagonist LY341495. In hemi‐parkinsonian rats, sensitivity towards LY354740 was reduced while that to NMDA was enhanced in the lesioned (denervated) compared with unlesioned striatum. Moreover, dizocilpine inhibited acetylcholine release in the lesioned compared with unlesioned striatum. Chronic treatment with l‐DOPA normalized sensitivity towards glutamatergic agonists. We conclude that striatal dopamine denervation results in plastic changes at group‐II metabotropic glutamate and NMDA receptors that may shift glutamatergic control of acetylcholine release towards facilitation. From a clinical perspective, l‐DOPA and NMDA antagonists appear effective in counteracting overactivity of striatal cholinergic interneurones associated with Parkinson's disease.
Novel glucocorticoid effects on acute inflammation in the CNS
Authors: Dinkel Klaus , MacPherson Anna , Sapolsky Robert M. 
Published: March 2003

AbstractThe CNS can mount an inflammatory reaction to excitotoxic insults that contributes to the emerging brain damage. Therefore, anti‐inflammatory drugs should be beneficial in neurological insults. In contrast, glucocorticoids (GCs), while known for their anti‐inflammatory effects, can exacerbate neurotoxicity in the hippocampus after excitotoxic insults. We investigated the effect of GCs on the inflammatory response after a neurological insult. Intact control (INT; intact stress response GC profile), adrenalectomized/GC‐supplemented (ADX; low basal GC profile) and GC‐treated (COR; chronically high GC profile) rats were injected with kainic acid into the hippocampal CA3 region. Lesion size was determined 8–72 h later. The inflammatory response was characterized using immunohistochemistry, RNAse protection assay and ELISA. The INT and COR rats developed larger CA3 lesions than ADX rats. We found that GCs surprisingly caused an increase in relative numbers of inflammatory cells (granulocytes, monocytes/macrophages and microglia). Additionally, mRNA and protein (IL‐1β and TNF‐α) levels of the pro‐inflammatory cytokines IL‐1α, IL‐1β and TNF‐α were elevated in COR rats compared with INT and ADX rats. These data strongly question the traditional view of GCs being uniformly anti‐inflammatory and could further explain how GCs worsen the outcome of neurological insults.
Long‐term increase in quality of nursing documentation: effects of a comprehensive intervention
Authors: Björvell Catrin , Wredling R. , Thorell‐Ekstrand I. 
Published: March 2003

Long‐term increase in quality of nursing documentation: effects of a comprehensive interventionThis study aimed to evaluate the longitudinal effects of a nursing‐documentation intervention on the quantity and quality of the nursing documentation in a sample of patient records at a university hospital in Stockholm, Sweden. In this quasi‐experimental longitudinal study, two hospital wards participated in a 2‐year intervention and a third ward was used for comparison. The intervention consisted of organizational changes and education regarding nursing documentation in accordance with the VIPS model, a model designed to structure nursing documentation. To evaluate the effect, patient records were audited at three different time points: before the intervention, directly after the intervention and 3 years after the intervention. A total of 269 patient records were used. The findings showed a significant score increase in quantity as well as in quality of the nursing documentation, in the intervention wards directly after the intervention, as compared with those from the comparison ward. The results suggests that a comprehensive intervention based on the VIPS model and including organizational support for registered nurses (RN) may improve nursing documentation in an acute care hospital setting.
Psychiatric care and home care service – an exploration of the professional world encountered by persons with long‐term mental illness
Authors: Nyström Maria , Lützén Kim 
Published: March 2003

Psychiatric care and home care service – an exploration of the professional world encountered by persons with long‐term mental illness This study focuses on the views of professional health care providers within a geographical district in Sweden. A total of 52 interviews with persons representing different professional levels within psychiatry and the social services were conducted. The purpose was to compare their understanding of what their responsibility entailed as well as their perceptions of goals and required competence. A content analysis, supplemented with interpretations within a hermeneutic tradition, showed that there are both similarities and differences within and between the two organizations. A common finding is that professionals with the least education are to a great extent responsible for the practical care of persons with long‐term mental illness. The implication of this finding is that it is important to be aware of this division of responsibility when developing psychiatric nursing and the home care services according to the needs of long‐term mentally ill patients.
Isolation and characterization of microsatellite loci from the Blanding’s turtle, Emydoidea blandingii
Authors: Osentoski M. F. , Mockford S. , Wright J. M. , Snyder M. , Herman T. B. , Hughes C. R. 
Published: March 2003

AbstractIndependent microsatellite development efforts at the University of Miami and Dalhousie University resulted in seven microsatellite loci for the Blanding’s turtle (Emydoidea blandingii). The level of polymorphism ranged from three to 15 alleles with observed heterozygosities ranging from 0.31 to 0.95. Cross species amplification suggests that these loci may have utility in other turtle species.