bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of alpha‐synuclein expression in alcohol‐preferring and ‐non preferring rats
Authors: Liang Tiebing , Carr Lucinda G. 
Published: August 2006

AbstractThe α‐synuclein (Snca) gene is expressed at higher levels in alcohol‐naïve, inbred alcohol‐preferring (iP) rats than in alcohol‐non preferring (iNP) rats. Snca modulates dopamine transmission and the dopamineregic system, which play a role in mediating the rewarding properties of alcohol consumption. Thus, understanding regulation of Snca gene expression could provide insight into the relationship of Snca and alcohol consumption. To study regulation of rat Snca expression, 1912 bp of the iP and iNP 5′‐regions were cloned and sequenced. 5′‐rapid amplification of cDNA ends (RACE), primer extension and RT‐PCR mapped three transcription start site clusters (clusters TSS1, TSS2 and TSS3), suggesting that the Snca proximal promoter region has a complex architecture. This proximal promoter region has three TATA‐less core promoters containing SP1 binding sites, initiator elements and downstream core promoter elements, which are often located in such promoters. Snca‐luc constructs transiently transfected into SK‐N‐SH neuroblastoma cells showed that the region from − 1912 to − 1746 contained a strong core promoter, and that the entire approximately 2 kb region had significant promoter activity. Five polymorphisms identified between the iP and iNP in the proximal promoter region did not influence differential expression between the strains. In contrast, a single nucleotide polymorphism (SNP) at + 679 in the 3′‐untranslated region (UTR) resulted in a 1.3‐fold longer half‐life of iP mRNA compared with iNP mRNA, which is consistent with the differential expression observed between the iP and iNP strains. These results suggest that regulation of rat Snca gene expression is complex and may contribute to alcohol preference in the iP rats.
Noncompensation in peptide/receptor gene expression and distinct behavioral phenotypes in VIP‐ and PACAP‐deficient mice
Authors: Girard Beatrice A. , Lelievre Vincent , Braas Karen M. , Razinia Tannaz , Vizzard Margaret A. , Ioffe Yevgeniya , Meskini Rajaa El , Ronnett Gabriele V. , Waschek James A. ,   Victor May
Published: August 2006

AbstractPituitary adenylate cyclase‐activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are closely related neurotrophic peptides of the secretin/glucagon family. The two peptides are derived from a common ancestral gene and share many functional attributes in neuronal development/regeneration which occur not only from overlapping receptor subtype signaling but also through common mechanisms regulating their expression. Although PACAP or VIP null mice have been generated for study, it is unclear whether the expression of the complementary peptide or their receptor systems are altered in a compensatory manner during nervous system development. By radioimmunoassay and quantitative PCR measurements, we first show that PACAP and VIP have very different temporal patterns of expression in developing postnatal mouse brain. In wild‐type animals, PACAP transcript and peptide levels increased rapidly 2‐ and 5‐fold, respectively, within 1 week of age. These levels at 1 week of age were maintained through adulthood. VIP transcript and peptide levels, by contrast, increased 25‐ and 50‐fold, respectively, over a later time course. In parallel studies of development, there were no apparent compensatory increases in brain VIP expression in the PACAP knockout animals, PACAP expression in the VIP‐deficient animals, or receptor mRNA levels in either genotype. To the contrary, there was evidence for developmental delays in the expression of peptide and receptor transcripts in the knockout animals. A series of behavioral and neurological tests demonstrated differences between the knockout genotypes, revealing some functional distinctions between the two genes. These results suggest that the PACAP and VIP have evolved to possess distinct biological activities and intimate that the respective knockout phenotypes represent deficits unmitigated by the actions of the complementary related peptide.
Neural stem cells from mouse forebrain are contained in a population distinct from the ‘side population’
Authors: Mouthon Marc‐André , Fouchet Pierre , Mathieu Céline , Sii‐Felice Karine , Etienne Olivier , Lages Céline Silva , Boussin François D. 
Published: August 2006

AbstractDeveloping and adult forebrains contain neural stem cells (NSCs) but no marker is available to highly purify them. When analysed by flow cytometry, stem cells from various tissues are enriched in a ‘side population’ (SP) characterized by the exclusion of the fluorescent dye Hoechst 33342. Here, we characterize the SP in embryonic, neonatal and adult forebrains, as well as in neurosphere cultures and we have determined whether this SP could be a source of enriched NSCs. By using specific inhibitors, we found that the SP from embryonic forebrain results from the activity of the ABCG2 transporter, a characteristic of other stem cells, whereas the SP from adult forebrain probably results from the ABCB1 transporter. SP cells from embryonic and adult forebrains, however, expressed a range of cell surface markers more consistent with a haematopoietic/endothelial origin than with a neural origin; NSC markers were mostly expressed on cells outside the SP (in the main population, MP). Moreover, assays for NSC growth in vitro showed that SP cells from embryonic and adult forebrains did not generate NSC‐derived colonies, whereas the MP did. We thus conclude that NSCs from developing and adult forebrains are not contained in the SP contrary to stem cells from other tissues.
MacMARCKS interacts with the metabotropic glutamate receptor type 7 and modulates G protein‐mediated constitutive inhibition of calcium channels
Authors: Bertaso Federica , Lill Yoriko , Airas José M. , Espeut Julien , Blahos Jaroslav , Bockaert Joël , Fagni Laurent , Betz Heinrich , El Far Oussama 
Published: August 2006

AbstractWe have previously shown that the interaction of Ca2+/calmodulin with the metabotropic glutamate receptor type 7 (mGluR7) promotes the G‐protein‐mediated inhibition of voltage‐sensitive Ca2+ channels (VSCCs) seen upon agonist activation. Here, we performed a yeast two‐hybrid screen of a new‐born rat brain cDNA library using the cytoplasmic C‐terminal tail of mGluR7 as bait and identified macrophage myristoylated alanine‐rich c‐kinase substrate (MacMARCKS) as a binding protein. The interaction was confirmed in vitro and in vivo by pull‐down assays, immunoprecipitation, and colocalization of mGluR7 and MacMARCKS in transfected HEK293 cells and cultured cerebellar granule cells. Binding of MacMARCKS to mGluR7 was antagonized by Ca2+/calmodulin. In neurons, cotransfection of MacMARCKS with mGluR7, but not mGluR7 mutants unable to bind MacMARCKS, reduced the G‐protein‐mediated tonic inhibition of VSCCs in the absence of mGluR7 agonist. These results suggest that competitive interactions of Ca2+/calmodulin and MacMARCKS with mGluR7 control the tonic inhibition of VSCCs by G‐proteins.
Growth hormone releasing peptide‐6 acts as a survival factor in glutamate‐induced excitotoxicity
Authors: Delgado‐Rubín de Célix Arancha , Chowen Julie A. , Argente Jesús , Frago Laura M. 
Published: August 2006

AbstractChronic systemic treatment given to adult male rats with growth hormone releasing peptide‐6, an agonist of the ghrelin receptor, increases insulin‐like growth factor I levels in various brain regions, including the hypothalamus and cerebellum. Furthermore, intracellular signalling cascades normally associated with anti‐apoptotic actions are activated in the same areas and are coincident with decreased basal cell death. Because abnormally high concentrations of glutamate can lead to overexcitation of neurones leading to cell damage and/or death, we investigated whether administration of growth hormone releasing peptide‐6 attenuates monosodium glutamate‐induced apoptosis in the rat hypothalamus and cerebellum. Glutamate increased activation of caspase 9 followed by cleavage of caspase 7, which in turn fragmented poly(ADP‐ribose) polymerase, terminating in cell death in both the hypothalamus and cerebellum. Growth hormone releasing peptide‐6 reversed glutamate‐induced cell death by decreasing activation of caspases 9 and 7 and poly(ADP‐ribose) polymerase fragmentation. These results provide a better understanding of the neuroprotective role of growth hormone secretagogues and the mechanisms involved.
The cell adhesion molecule neuroplastin‐65 inhibits hippocampal long‐term potentiation via a mitogen‐activated protein kinase p38‐dependent reduction in surface expression of GluR1‐containing glutamate receptors
Authors: Empson Ruth M. , Buckby Lucy E. , Kraus Michaela , Bates Katharine J. , Crompton Mark R. , Gundelfinger Eckart D. , Beesley Philip W. 
Published: August 2006

AbstractNeuroplastin‐65 is a brain‐specific, synapse‐enriched member of the immunoglobulin (Ig) superfamily of cell adhesion molecules. Previous studies highlighted the importance of neuroplastin‐65 for long‐term potentiation (LTP), but the mechanism was unclear. Here, we show how neuroplastin‐65 activation of mitogen‐activated protein kinase p38 (p38MAPK) modified synapse strength by altering surface glutamate receptor expression. Organotypic hippocampal slice cultures treated with the complete extracellular fragment of neuroplastin‐65 (FcIg1‐3) sustained an increase in the phosphorylation of p38MAPK and an inability to induce LTP at hippocampal synapses. The LTP block was reversed by application of the p38MAPK inhibitor SB202190, suggesting that p38MAPK activation occurred downstream of neuroplastin‐65 binding and upstream of the loss of LTP. Further investigation revealed that the mechanism underlying neuroplastin‐65‐dependent prevention of LTP was a p38MAPK‐dependent acceleration of the loss of surface‐exposed glutamate receptor subunits that was reversed by pretreatment with the p38MAPK inhibitor SB202190. Our results indicate that neuroplastin‐65 binding and associated stimulation of p38MAPK activity are upstream of a mechanism to control surface glutamate receptor expression and thereby influence plasticity at excitatory hippocampal synapses.
Molecular basis of neuroendocrine cell type‐specific expression of the chromogranin B gene: crucial role of the transcription factors CREB, AP‐2, Egr‐1 and Sp1
Authors: Mahapatra Nitish R. , Mahata Manjula , Ghosh Sajalendu , Gayen Jiaur R. , O'Connor Daniel T. , Mahata Sushil K. 
Published: August 2006

AbstractThe molecular basis of neuroendocrine‐specific expression of chromogranin B gene (Chgb) has remained elusive. Utilizing wild‐type and mutant Chgb promoter/luciferase reporter constructs, this study established a crucial role for the cAMP response element (CRE) box at −102/−95 bp in endocrine [rat pheochromocytoma (chromaffin) cell line (PC12) and rat pituitary somatotrope cell line (GC)] and neuronal [rat dorsal root ganglion/mouse neuroblastoma hybrid cell line (F‐11), cortical and hippocampal primary neurons] cells. Additionally, G/C‐rich domains at −134/−127, −125/−117 and −115/−110 bp played especially important roles for endocrine‐specific expression of the Chgb gene. Co‐transfection of expression plasmids for CREB, activator protein‐2 (transcription factor) (AP‐2), early growth response protein (transcription factor) (Egr‐1) or specificity protein 1 (transcription factor) (Sp1) with the Chgb promoter constructs trans‐activated expression of the Chgb gene. Nuclear extracts from either PC12 or F‐11 cells formed specific complexes with the Chgb (−110/−87 bp) (CRE) oligonucleotide, which were either supershifted or disrupted by anti‐CREB antibodies. In addition PC12 nuclear extracts also formed a specific complex with a Chgb (−140/−104‐bp) oligonucleotide containing three G/C‐rich regions, which was dose‐dependently disrupted by anti‐AP‐2, anti‐Egr‐1 or anti‐Sp1 antibodies; indeed, any one of these three antibodies completely abolished the complex, suggesting that all three factors bind the region simultaneously, at least in vitro. Chromatin immunoprecipitation assays documented the binding of the transcription factors CREB, AP‐2, Egr‐1 and Sp1 to the chromosomal Chgb gene promoter in vivo in PC12 cells within the context of chromatin. We conclude that the neuroendocrine‐specific expression of Chgb is mediated by the CRE and G/C boxes in cis and the transcription factors CREB, AP‐2, Egr‐1 and Sp1 in trans.
The anxiety‐like phenotype of 5‐HT1A receptor null mice is associated with genetic background‐specific perturbations in the prefrontal cortex GABA–glutamate system
Authors: Bruening S. , Oh E. , Hetzenauer A. , Escobar‐Alvarez S. , Westphalen R. I. , Hemmings H. C. , Singewald N. , Shippenberg T. , Toth M. 
Published: August 2006

AbstractA deficit in the serotonin 5‐HT1A receptor has been found in panic and post‐traumatic stress disorders, and genetic inactivation of the receptor results in an anxiety‐like phenotype in mice on both the C57Bl6 and Swiss–Webster genetic backgrounds. Anxiety is associated with increased neuronal activity in the prefrontal cortex and here we describe changes in glutamate and GABA uptake of C57Bl6 receptor null mice. Although these alterations were not present in Swiss–Webster null mice, we have previously reported reductions in GABAA receptor expression in these but not in C57Bl6 null mice. This demonstrates that inactivation of the 5‐HT1A receptor elicits different and genetic background‐dependent perturbations in the prefrontal cortex GABA/glutamate system. These perturbations can result in a change in the balance between excitation and inhibition, and indeed both C57Bl6 and Swiss–Webster null mice show signs of increased neuronal excitability. Because neuronal activity in the prefrontal cortex controls the extent of response to anxiogenic stimuli, the genetic background‐specific perturbations in glutamate and GABA neurotransmission in C57Bl6 and Swiss–Webster 5‐HT1A receptor null mice may contribute to their shared anxiety phenotype. Our study shows that multiple strains of genetically altered mice could help us to understand the common and individual features of anxiety.
Uracil nucleotides stimulate human neural precursor cell proliferation and dopaminergic differentiation: involvement of MEK/ERK signalling
Authors: Milosevic Javorina , Brandt Annett , Roemuss Ute , Arnold Antje , Wegner Florian , Schwarz Sigrid C. , Storch Alexander , Zimmermann Herbert , Schwarz Johannes 
Published: August 2006

AbstractIsolation and propagation of neural stem cells derived from human brain tissue uniquely enables the study of human neurogenesisin vitro. In addition,ex vivo‐expanded human neural stem/precursor cells (NPCs) may offer novel therapeutic strategies. We investigated the effects of extracellular nucleotides on the proliferation and differentiation of human mesencephalic neural stem/precursor cells (hmNPCs). When combined with the mitogens epidermal growth factor and fibroblast growth factor 2, UTP (1 µm) boosted proliferation of hmNPCs as shown by increased expression of the proliferation marker proliferating cell nuclear antigen (330%). UTP‐induced proliferation was abrogated by the preferential P2Y receptor blocker pyridoxal phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS). UTP also stimulated dopaminergic differentiation. Treatment with UTP (100 µm) increased the number of tyrosine hydroxylase (TH)‐positive cells and TH protein by 267 and 319% respectively. UTP‐stimulated dopaminergic differentiation of hmNPCs was blocked by the P2 receptor antagonists suramin (10 µm) and PPADS (100 µm). In addition, UDP (1 µm) enhanced TH protein expression by 194%. During differentiation, treatment with UTP stimulated the extracellular signal‐regulated kinase (ERK) pathway. Both ERK1/2 phosphorylation and dopaminergic differentiation were inhibited by U0126, a selective ERK kinase inhibitor, as well as by suramin. When other P2 receptor agonists (ATP, ADP and adenosine 5′‐O‐(2‐thiophosphate) (ADPβS); all 100 µm) were applied, both proliferation and dopaminergic differentiation of NPCs were compromised. We conclude that uracil nucleotides exert specific P2 receptor‐mediated effects on midbrain‐derived human NPCs, and may be used to enhance both proliferation and dopaminergic differentiation.
Glutamate‐stimulated ATP release from spinal cord astrocytes is potentiated by substance P
Authors: Werry Eryn L. , Liu Guo Jun , Bennett Max R. 
Published: August 2006

AbstractATP has recently emerged as a key molecule mediating pathological pain. The aim of this study was to examine whether spinal cord astrocytes could be a source of ATP in response to the nociceptive neurotransmitters glutamate and substance P. Glutamate stimulated ATP release from these astrocytes and this release was greatly potentiated by substance P, even though substance P alone did not elicit ATP release. Substance P also potentiated glutamate‐induced inward currents, but did not cause such currents alone. When glutamate was applied alone it acted exclusively through α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐proprionate receptors to stimulate Ca2+ influx‐dependent ATP release. However, when substance P was co‐applied with glutamate, ATP release could be elicited by activation of NMDA and metabotropic glutamate receptors. Activation of neurokinin receptor subtypes, protein kinase C and phospholipases A2, C and D were needed for substance P to bring about its effects. These results suggest that astrocytes may be a major source of ATP in the spinal cord on activation of nerve fibres that release substance P and glutamate.
Well‐being of 12‐year‐old children related to interpersonal relations, health habits and mental distress
Authors: Lindberg Lene , Swanberg Inga 
Published: August 2006

Aim:  The main purpose was to examine if interpersonal relations, mental distress, somatic symptoms and health behaviours could be protective or risk factors for the subjective well‐being of 12‐year‐old school children.Methods:  After ethical and parental permission a questionnaire was completed by 807 pupils in the sixth grade of 18 randomised schools in seven rural and urban districts in the north‐west area of Stockholm. The questionnaire was a modified version of the WHO Health Behaviour in School‐Ages Children Study and the Youth Self‐Report Questionnaire. Well‐being was measured by the question, ‘How are you these days'? Measures of protective or risk factors were relations to parents, teacher/schoolwork and peers, eating and safety habits, somatic symptoms, anxious/depressed and aggressiveness.Results:  Logistic regressions were performed with well‐being as dependent variable before and after adjustment for gender, which was the only significant background factor. Finally, a multiple logistic regression analysis was conducted with gender and the six significantly related predictors as independent variables. In the multiple model, relations to teacher/school and peers, eating habits, anxious/depressed and somatic symptoms were associated with well‐being and yielded significant odds ratios.Conclusions:  Relations to teacher/school, relations to peers and good eating habits could be protective factors for subjective well‐being, while somatic and anxious/depressed symptoms may be risk factors for ill‐being. This indicates an increased need for interpersonal relations and mental health‐oriented, promotive interventions in schools.
Nursing advocacy: how is it defined by patients and nurses, what does it involve and how is it experienced?
Authors: Vaartio Heli , Leino‐Kilpi Helena , Salanterä Sanna , Suominen Tarja 
Published: August 2006

The study's rationale:  Advocacy is an integral part of nursing. However, there is a scarcity of empirical evidence on nursing advocacy process and most of that evidence concerns nurses’ views on the care of certain vulnerable patient groups in acute care settings. Before nursing practice can truly adopt advocacy as an inherent and natural part of nursing, a clearer understanding is needed of how it is defined and what activities are needed to accomplish advocacy.Aims and objectives:  The aim was to describe the way that nursing advocacy is defined, the activities through which nursing advocacy is accomplished and the way that nursing advocacy is experienced by patients and nurses.Methodological design and justification:  Based on a qualitative approach, the study was limited to adult patients experiencing procedural pain in somatic care. Interviews were conducted in a convenience sample of patients (n = 22) and nurses (n = 21) from four medical and four surgical wards in Finland. A qualitative content analysis of the tape‐recorded data was then carried out.Ethical issues and approval:  The appropriate ethical principles were followed. All the participants gave their informed consent and formal approval for conducting the research was obtained according to national and local directives.Results:  Nursing advocacy seems to integrate aspects of individuality, professionalism and experiences of empowering, exceptional care. It is not a single event, but a process of analysing, counselling, responding, shielding and whistleblowing activities in clinical nursing practice.Conclusions:  In nursing practice the abstract concept of nursing advocacy finds expression in voicing responsiveness, which integrates an acknowledged professional responsibility for and active involvement in supporting patients’ needs and wishes.
Health‐related quality of life in women patients with borderline personality disorder
Authors: Perseius Kent‐Inge , Andersson Eva , Åsberg Marie , Samuelsson Mats 
Published: August 2006

Objectives:  The aims of the study were to: (i) test the reliability of a health‐related quality of life (HRQOL) instrument [Swedish Health‐Related Quality of Life Survey (SWED‐QUAL)] on women patients with borderline personality disorder (BPD); (ii) compare their HRQOL to a normal population group comparable in age; and (iii) test for subgroup differences in HRQOL considering psychiatric DSM axis‐I comorbidity.Method:  The study was conducted in connection to a randomized, controlled trial of psychotherapy for women BPD patients. Seventy‐five women with BPD diagnosis were administered the SWED‐QUAL. Statistic reliability was evaluated with inter‐item correlations, total‐item correlations and internal consistency criterions. The BPD patients’ SWED‐QUAL results were compared with data extracted from a published study and subgroup differences due to axis‐I comorbidity were analysed.Results and conclusions:  SWED‐QUAL could be considered as an instrument with acceptable reliability when assessing HRQOL in BPD patients. The BPD patients suffered significant impairments in HRQOL overall health dimensions compared to normal population. There were no subgroup differences due to axis‐I comorbidity, which indicate that BPD in itself might be a predictor of substantial HRQOL impairment.