bluuebunny/crossref_metadata_2025_split huggingface dataset:
An adenosine A2A receptor agonist induces sleep by increasing GABA release in the tuberomammillary nucleus to inhibit histaminergic systems in rats
Authors: Hong Zong‐Yuan , Huang Zhi‐Li , Qu Wei‐Min , Eguchi Naomi , Urade Yoshihiro , Hayaishi Osamu 
Published: March 2005

AbstractThe adenosine A2A receptor (A2AR) has been demonstrated to play a crucial role in the regulation of the sleep process. However, the molecular mechanism of the A2AR‐mediated sleep remains to be elucidated. Here we used electroencephalogram and electromyogram recordings coupled with in vivo microdialysis to investigate the effects of an A2AR agonist, CGS21680, on sleep and on the release of histamine and GABA in the brain. In freely moving rats, CGS21680 applied to the subarachnoid space underlying the rostral basal forebrain significantly promoted sleep and inhibited histamine release in the frontal cortex. The histamine release was negatively correlated with the amount of non‐rapid eye movement sleep (r = − 0.652). In urethane‐anesthetized rats, CGS21680 inhibited histamine release in both the frontal cortex and medial pre‐optic area in a dose‐dependent manner, and increased GABA release specifically in the histaminergic tuberomammillary nucleus but not in the frontal cortex. Moreover, the CGS21680‐induced inhibition of histamine release was antagonized by perfusion of the tuberomammillary nucleus with a GABAA antagonist, picrotoxin. These results suggest that the A2AR agonist induced sleep by inhibiting the histaminergic system through increasing GABA release in the tuberomammillary nucleus.
Induction of galanin receptor‐1 (GalR1) expression in external granule cell layer of post‐natal mouse cerebellum
Authors: Jungnickel S. R.‐F. , Yao M. , Shen P.‐J. , Gundlach A. L. 
Published: March 2005

AbstractGalanin is a modulator of fast transmission in adult brain and recent evidence suggests that it also acts as a trophic factor during neurogenesis and neural injury and repair. Previous studies in our laboratory have identified galanin mRNA in Purkinje cells of adult and developing rat (but not adult mouse) cerebellum; and galanin‐binding sites in adult mouse (but not rat) cerebellum. The post‐natal development of the cerebellum provides a unique and convenient model for the investigation of developmental processes and to learn more about putative cerebellar galanin systems, the current study examined the presence and distribution of galanin‐like‐immunoreactivity (– LI), [125I]‐galanin binding sites and galanin receptor‐1 (GalR1) mRNA in post‐natal mouse cerebellum. Using autoradiography and in situ hybridization, [125I]‐galanin binding sites and GalR1 mRNA were first detected on post‐natal day 10 (P10) in the external germinal layer of all lobes and high levels were maintained until P14. Quantitative real‐time PCR assays detected GalR1 mRNA in whole cerebellum across the post‐natal period, with a strong induction and peak of expression at P10. Assessment of galanin levels in whole cerebellum by radioimmunoassay revealed relatively similar concentrations from P5 to P20 and in adult mice (80–170 pg/mg protein), with a significantly higher concentration (250 pg/mg, p < 0.01) detected at P3. These concentrations were some four‐ to six‐fold lower than those in adult forebrain samples. Using immunohistochemistry, galanin‐like‐immuno‐reactivity was observed in prominent fibrous elements within the white matter tracts of the cerebellum at P3–5 and in more punctate elements in the internal granule cell layer and associated with the Purkinje cell layer at P12 and P20. Increased levels of GalR1 mRNA and galanin binding (attributed to GalR1) in the external granule cell layer at P10–12/(14) coincide with granule cell migration from the external to the inner granule cell layer and together with demonstrated effects of other neuropeptide‐receptor systems suggest a role for GalR1 signalling in regulating this or related developmental processes.
Purified Wnt‐5a increases differentiation of midbrain dopaminergic cells and dishevelled phosphorylation
Authors: Schulte Gunnar , Bryja Vítězslav , Rawal Nina , Castelo‐Branco Goncalo , Sousa Kyle M. , Arenas Ernest 
Published: March 2005

AbstractThe Wnt family of lipoproteins regulates several aspects of the development of the nervous system. Recently, we reported that Wnt‐3a enhances the proliferation of midbrain dopaminergic precursors and that Wnt‐5a promotes their differentiation into dopaminergic neurones. Here we report the purification of hemagglutinin‐tagged Wnt‐5a using a three‐step purification method similar to that previously described for Wnt‐3a. Haemagglutinin‐tagged Wnt‐5a was biologically active and induced the differentiation of immature primary midbrain precursors into tyrosine hydroxylase‐positive dopaminergic neurones. Using a substantia nigra‐derived dopaminergic cell line (SN4741), we found that Wnt‐5a, unlike Wnt‐3a, did not promote β‐catenin phosphorylation or stabilization. However, both Wnt‐5a and Wnt‐3a activated dishevelled, as assessed by a phosphorylation‐dependent mobility shift. Moreover, the activity of Wnt‐5a on dishevelled was blocked by pre‐treatment with acyl protein thioesterase‐1, indicating that palmitoylation of Wnt‐5a is necessary for its function. Thus, our results suggest that Wnt‐3a and Wnt‐5a, respectively, activate canonical and non‐canonical Wnt signalling pathways in ventral midbrain dopaminergic cells. Furthermore, we identify dishevelled as a key player in transducing both Wnt canonical and non‐canonical signals in dopaminergic cells.
Changes in phosphorylation of the NMDA receptor in the rat hippocampus induced by status epilepticus
Authors: Niimura M. , Moussa R. , Bissoon N. , Ikeda‐Douglas C. , Milgram N. W. , Gurd J. W. 
Published: March 2005

AbstractSystemic administration of pilocarpine preceded by lithium induces status epilepticus (SE) that results in neurodegeneration and may lead to the development of spontaneous recurrent seizures. We investigated the effect of Li/pilocarpine‐induced SE on phosphorylation of the NMDA receptor in rat hippocampus. Phosphorylation of NR1 by PKC on Ser890 was decreased to 45% of control values immediately following 1 h of SE. During the first 3 h following the termination of SE, phosphorylation of Ser890 increased 4‐fold before declining to control values by 24 h. Phosphorylation of NR1 by PKA was also depressed relative to controls immediately following SE and transiently increased above control values upon the termination of SE. SE was accompanied by a general increase in tyrosine phosphorylation of hippocampal proteins that lasted for several hours following the termination of seizures. Tyrosine phosphorylation of the NR2A and NR2B subunits of the NMDAR increased 3–4‐fold over control values during SE, continued to increase during the first hour following SE and then declined to control levels by 24 h. SE resulted in the activation of Src and Pyk2 associated with the postsynaptic apparatus, suggesting a role for these enzymes in the SE‐induced increase in tyrosine phosphorylation. Changes in phosphorylation of the NMDA receptor may play a role in the pathophysiological consequences of SE.
Pure albumin is a potent trigger of calcium signalling and proliferation in microglia but not macrophages or astrocytes
Authors: Hooper Claudie , Taylor Deanna L. , Pocock Jennifer M. 
Published: March 2005

AbstractMicroglial activation is implicated in the neurotoxicity of neurodegenerative diseases. Raised intracerebral levels of albumin are associated with the pathology of Alzheimer's disease, multiple sclerosis, and stroke where blood–brain barrier damage is evident. We report here that treatment of primary cultured microglia and the N9 microglial cell line with pure albumin, or albumin in which fatty acids and immunoglobulins remain attached (fraction V), induced a rise in intracellular calcium. This rise in intracellular calcium was mediated via Src tyrosine kinase and phospholipase C. The albumin‐induced calcium response was coupled to microglial proliferation, which was prevented by BAPTA, U73122 or PP2 but not mimicked by thapsigargin. In contrast, peritoneal macrophages were resistant to albumin‐ or fraction V‐induced calcium responses and proliferation, whilst primary cultured astrocytes or the TSA‐3 astrocyte cell line were responsive to fraction V albumin but not pure albumin. Furthermore, cerebellar granule neurones did not respond to albumin. These data suggest that albumin may play a role in microglial activation in pathological situations involving blood–brain barrier impairment, and that the specific responses of microglia to albumin allow a distinction to be made between the signalling responses of microglia, blood‐borne macrophages, astrocytes and neurones.
Specific induction of macrophage inflammatory protein 1‐α in glial cells of Sandhoff disease model mice associated with accumulation of N‐acetylhexosaminyl glycoconjugates
Authors: Tsuji Daisuke , Kuroki Aya , Ishibashi Yasuhiro , Itakura Tomohiro , Kuwahara Jun , Yamanaka Shoji , Itoh Kohji 
Published: March 2005

AbstractSandhoff disease is a lysosomal storage disease caused by simultaneous deficiencies of β‐hexosaminidase A (HexA; αβ) and B (HexB; ββ), due to a primary defect of the β‐subunit gene (HEXB) associated with excessive accumulation of GM2 ganglioside (GM2) and oligosaccharides with N‐acetylhexosamine residues at their non‐reducing termini, and with neurosomatic manifestations. To elucidate the neuroinflammatory mechanisms involved in its pathogenesis, we analyzed the expression of chemokines in Sandhoff disease model mice (SD mice) produced by disruption of the murine Hex β‐subunit gene allele (Hexb–/–). We demonstrated that chemokine macrophage inflammatory protein‐1 α (MIP‐1α) was induced in brain regions, including the cerebral cortex, brain stem and cerebellum, of SD mice from an early stage of the pathogenesis but not in other systemic organs. On the other hand, little changes in other chemokine mRNAs, including those of RANTES (regulated upon activation, normal T expressed and secreted), MCP‐1 (monocyte chemotactic protein‐1), SLC (secondary lymphoid‐tissue chemokine), fractalkine and SDF‐1 (stromal derived factor‐1), were detected. Significant up‐regulation of MIP‐1α mRNA and protein in the above‐mentioned brain regions was observed in parallel with the accumulation of natural substrates of HexA and HexB. Immunohistochemical analysis revealed that MIP‐1α‐immunoreactivity (IR) in the above‐mentioned brain regions of SD mice was co‐localized in Iba1‐IR‐positive microglial cells and partly in glial fibrillary acidic protein (GFAP)‐IR‐positive astrocytes, in which marked accumulation of N‐acetylglucosaminyl (GlcNAc)‐oligosaccharides was observed from the presymptomatic stage of the disease. In contrast, little MIP‐1α‐IR was observed in neurons in which GM2 accumulated predominantly. These results suggest that specific induction of MIP‐1α might coincide with the accumulation of GlcNAc‐oligosaccharides due to a HexB deficiency in resident microglia and astrocytes in the brains of SD mice causing their activation and acceleration of the progressive neurodegeneration in SD mice.
Protection by cholesterol‐extracting cyclodextrins: a role for N‐methyl‐d‐aspartate receptor redistribution
Authors: Abulrob Abedelnasser , Tauskela Joseph S. , Mealing Geoff , Brunette Eric , Faid Karim , Stanimirovic Danica 
Published: March 2005

AbstractCyclodextrins (CDs) are cyclic oligosaccharides composed of a lipophilic central cavity and a hydrophilic outer surface. Some CDs are capable of extracting cholesterol from cell membranes and can affect function of receptors and proteins localized in cholesterol‐rich membrane domains. In this report, we demonstrate the neuroprotective activity of some CD derivatives against oxygen–glucose deprivation (OGD), N‐methyl‐d‐aspartic acid (NMDA) and glutamate in cortical neuronal cultures. Although all CDs complexed with NMDA or glutamate, only β‐, methylated β‐ and sulfated β‐CDs displayed neuroprotective activity and lowered cellular cholesterol. Only CDs that lowered cholesterol levels redistributed the NMDA receptor NR2B subunit, PSD‐95 (postsynaptic density protein 95 kDa) and neuronal nitric oxide synthase (nNOS) from Triton X‐100 insoluble membrane domains to soluble fractions. Cholesterol repletion counteracted the ability of methylated β‐CD to protect against NMDA toxicity, and reversed NR2B, PSD‐95 and nNOS localization to Triton X‐100 insoluble membrane fraction. Surprisingly, neuroprotective CDs had minimal effect on NMDA receptor‐mediated increases in intracellular Ca2+ concentration ([Ca2+]i), but did suppress OGD‐induced increases in [Ca2+]i. β‐CD, but not Mβ‐CD, also caused a slight block of NMDA‐induced currents, suggesting a minor contribution to neuroprotection by direct action on NMDA receptors. Taken together, data suggest that cholesterol extraction from detergent‐resistant microdomains affects NMDA receptor subunit distribution and signal propagation, resulting in neuroprotection of cortical neuronal cultures against ischemic and excitotoxic insults. Since cholesterol‐rich membrane domains exist in neuronal postsynaptic densities, these results imply that synaptic NMDA receptor subpopulations underlie excitotoxicity, which can be targeted by CDs without affecting overall neuronal Ca2+ levels.
Inhibition of microglial inflammation by the MLK inhibitor CEP‐1347
Authors: Lund Søren , Porzgen Peter , Mortensen Anne Louise , Hasseldam Henrik , Bozyczko‐Coyne Donna , Morath Siegfried , Hartung Thomas , Bianchi Marina , Ghezzi Pietro , Bsibsi Malika , Dijkstra Sipke , Leist Marcel 
Published: March 2005

AbstractCEP‐1347 is a potent inhibitor of the mixed lineage kinases (MLKs), a distinct family of mitogen‐activated protein kinase kinase kinases (MAPKKK). It blocks the activation of the c‐Jun/JNK apoptotic pathway in neurons exposed to various stressors and attenuates neurodegeneration in animal models of Parkinson's disease (PD). Microglial activation may involve kinase pathways controlled by MLKs and might contribute to the pathology of neurodegenerative diseases. Therefore, the possibility that CEP‐1347 modulates the microglial inflammatory response [tumour necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and monocyte chemotactic protein‐1 (MCP‐1)] was explored. Indeed, the MLK inhibitor CEP‐1347 reduced cytokine production in primary cultures of human and murine microglia, and in monocyte/macrophage‐derived cell lines, stimulated with various endotoxins or the plaque forming peptide Aβ1–40. Moreover, CEP‐1347 inhibited brain TNF production induced by intracerebroventricular injection of lipopolysaccharide in mice. As expected from a MLK inhibitor, CEP‐1347 acted upstream of p38 and c‐Jun activation in microglia by dampening the activity of both pathways. These data imply MLKs as important, yet unrecognized, modulators of microglial inflammation, and demonstrate a novel anti‐inflammatory potential of CEP‐1347.
Deep venous thrombosis and pulmonary embolism following physical restraint
Authors: Laursen S. B. , Jensen T. N. , Bolwig T. , Olsen N. V. 
Published: March 2005

Objective:  We describe a case of deep venous thrombosis (DVT) and pulmonary embolism (PE) following the use of physical restraint in a patient with a diagnosis of acute delusional psychotic disorder.Method:  A new case report of DVT and PE associated with prolonged physical restraint is presented. The literature on physical restraint, DVT, and PE was reviewed using a search of Medline and Psychinfo from 1966 to the present.Results:  Four other reported cases of DVT and PE were found in association with physically restrained patients.Conclusion:  Risk of DVT and PE in association with immobilization during physical restraint may occur in spite of no pre‐existing risk factors. Medical guidelines for the prevention of thrombosis following physical restraint are presented. Despite the absence of controlled trials of treatment effectiveness, the catastrophic outcome of DVT and PE warrants early and vigorous intervention in patients undergoing physical restraint.
Trauma exposure and post‐traumatic stress disorder in the general population
Authors: Frans Ö. , Rimmö P.‐A. , Åberg L. , Fredrikson M. 
Published: March 2005

Objective:  To examine the lifetime prevalence of trauma experiences and post‐traumatic stress disorder (PTSD).Method:  Questionnaire‐assessed PTSD, the type of traumatic event experienced, perceived trauma impact, and trauma frequency in 1824 randomly selected men and women.Results:  PTSD lifetime prevalence was estimated at 5.6% with a 1 : 2 male‐to‐female ratio, in spite of men reporting greater trauma exposure. The highest PTSD risk was associated with sexual and physical assault, robbery and multiple trauma experiences. Controlling for trauma type did not account for gender differences, while controlling for experienced distress did.Conclusion:  The conditional probability for PTSD varied as a function of trauma type, frequency and impact of the event, with increased rates associated with prevalent trauma exposure and higher perceived distress. The latter accounted for the gender effect, suggesting that gender differences in PTSD in part represent a generally greater vulnerability to stress in women.
Depression and chronic obstructive pulmonary disease (COPD). Impact on survival
Authors: Stage K. B. , Middelboe T. , Pisinger C. 
Published: March 2005

Objective:  To determine if the presence of depression in patients suffering from chronic obstructive pulmonary disease (COPD) would have an independent impact on mortality.Method:  Prospective evaluation of the impact of depression according to the ICD‐10 criteria for depression. Cox proportional hazards regression was used to evaluate the independent impact of depression after controlling for significant univariate clinical predictors in the data set. Consenting out‐patients (n = 49) who meet the criteria for COPD between September 1997 and September 1998. There were no age limits (range: 53–90 years). The sample was 67% female. Survival status at follow‐up after a mean of 803 days was measured.Results:  At follow‐up, 16 patients had died. Depression significantly reduced the mortality risk at follow‐up (hazard ratio, 0.30; 95% confidence interval, 0.10–0.93; P = 0.037). The impact of depression remained after control for forced expiratory volume during the first second (FEV1), the only multivariate significant predictor of mortality in the data set (hazard ratio, 0.27; 95% confidence interval, 0.09–0.84; P = 0.024).Conclusion:  Depression in out‐patients suffering from COPD appears to be an independent protector for mortality. Additional studies in larger samples are needed to replicate this finding and to determine possible underlying pathogenetic mechanisms.
Selective serotonin reuptake inhibitor antidepressants and the risk of suicide: a controlled forensic database study of 14 857 suicides
Authors: Isacsson G. , Holmgren P. , Ahlner J. 
Published: March 2005

Objective:  To test the hypothesis that selective serotonin reuptake inhibitor (SSRI) antidepressants may have a suicide emergent effect, particularly in children and adolescents.Method:  Detections of different antidepressants in the forensic toxicological screening of 14 857 suicides were compared with those in 26 422 cases of deaths by accident or natural causes in Sweden 1992–2000.Results:  There were 3411 detections of antidepressants in the suicides and 1538 in the controls. SSRIs had lower odds ratios than the other antidepressants. In the 52 suicides under 15 years, no SSRIs were detected. In 15–19‐year age group, SSRIs had lower relative risk in suicides compared with non‐SSRIs.Conclusion:  The hypothesis that treatment of depressed individuals with SSRIs leads to an increased risk of suicide was not supported by this analysis of the total suicidal outcome of the nationwide use of SSRIs in Sweden over a period of 9 years, either in adults or in children or adolescents.
The Development of a Heterogeneous Composite Bipolar Plate of a Proton Exchange Membrane Fuel Cell
Authors: Lee Ming-San , Chen Long-Jeng , He Zheng-Ru , Yang Shih-Hong 
Published: March 2005

AbstractA new high performance, low cost heterogeneous composite bipolar plate has been developed. Unlike the well publicized carbon composite bipolar plate, in which graphite powder and plastics are mixed thoroughly, the new plate has its “ribs” made of flexible and loose carbon fiber bunches while the rest of the plate is plain plastic. This design has brought many advantages: low contact resistance acquired under very low compression force, less stack weight and volume, full electrode utilization, and thus high performance and low cost. It also eliminates the need for supplementary devices for fuel circulation among cells in a stack and makes DMFC portable.
FREE SYMMETRIC AND UNITARY PAIRS IN DIVISION RINGS WITH INVOLUTION
Authors: FERREIRA VITOR O. , GONÇALVES JAIRO Z. , MANDEL ARNALDO 
Published: March 2005

Let D be a division ring with an involution and characteristic different from 2. Then, up to a few exceptions, D contains a pair of symmetric elements freely generating a free subgroup of its multiplicative group provided that (a) it is finite-dimensional and the center has a finite sufficiently large transcendence degree over the prime field, or (b) the center is uncountable, but not algebraically closed in D. Under conditions (a), if the involution is of the first kind, it is also shown that the unitary subgroup of the multiplicative group of D contains a free subgroup, with one exception. The methods developed are also used to exhibit free subgroups in the multiplicative group of a finite-dimensional division ring provided the center has a sufficiently large transcendence degree over its prime field.
REGULARITY CONSTANTS OF THE STOKES PROBLEM: APPLICATION TO FINITE-ELEMENT METHODS ON CURVED DOMAINS
Authors: AYUSO B. , GARCÍA-ARCHILLA B. 
Published: March 2005

For bounded smooth domains, we study how the solution of the Stokes problem is bounded in terms of the data when the domain changes. We show that standard bounds for a fixed domain hold with the same constant for wide classes of domains. This is done by first reviewing the original results of Cattabriga and then, in terms of geometric properties of the domains, by specifying when to apply Cattabriga's intermediate results. We do the same with standard strong extension and trace theorems. We apply these results to an elegant technique of analysis due to Wahlbin to overcome the disparity between a curved domain and the domains where finite-element computations are carried out in practice without resorting to numerical quadrature.