bluuebunny/crossref_metadata_2025_split huggingface dataset:
Excitotoxicity‐related endocytosis in cortical neurons
Authors: Vaslin A. , Puyal J. , Borsello T. , Clarke P. G. H. 
Published: May 2007

AbstractRecent studies showed that endocytosis is enhanced in neurons exposed to an excitototoxic stimulus. We here confirm and analyze this new phenomenon using dissociated cortical neuronal cultures. NMDA‐induced uptake (FITC‐dextran or FITC or horseradish peroxidase) occurs in these cultures and is due to endocytosis, not to cell entry through damaged membranes; it requires an excitotoxic dose of NMDA and is dependent on extracellular calcium, but occurs early, while the neuron is still intact and viable. It involves two components, NMDA‐induced and constitutive, with different characteristics. Neither component involves specific binding of the endocytosed molecules to a saturable receptor. Strikingly, molecules internalized by the NMDA‐induced component are targeted to neuronal nuclei. This component, but not the constitutive one, is blocked by a c‐Jun N‐terminal protein kinase inhibitor. In conclusion, an excitotoxic dose of NMDA triggers c‐Jun N‐terminal protein kinase‐dependent endocytosis in cortical neuronal cultures, providing an in vitro model of the excitotoxicity‐induced endocytosis reported in intact tissues.
Transcriptome analysis reveals altered cholesterol metabolism during the neurodegeneration in mouse scrapie model
Authors: Xiang Wei , Hummel Manuela , Mitteregger Gerda , Pace Claudia , Windl Otto , Mansmann Ulrich , Kretzschmar Hans A. 
Published: May 2007

AbstractTo identify the dynamic transcriptional alterations in CNS during the development of prion disease, brains of scrapie‐infected mice and age‐matched, mock‐inoculated controls were analyzed immediately before inoculation and at different time points post‐inoculation using Affymetrix microarray technique. A total of 449 probe sets, representing 430 genes, showed differential expression between scrapie‐ and mock‐inoculated mice over the time course. These genes could be separated into two clusters according to expression patterns: the genes in cluster 1 demonstrated lower mRNA levels in scrapie‐infected brains when compared with mock‐inoculated brains, whereas genes in cluster 2 showed higher mRNA levels in scrapie‐infected brains. Functional analysis of differentially expressed genes revealed the most severely affected biological process: cholesterol metabolism. The expression patterns of the cholesterol‐related genes indicated an inhibited cholesterol synthesis in the diseased brains. Conspicuously, a number of cluster 1 genes, including some of cholesterol‐related genes, showed not only decreasing mRNA levels in scrapie‐infected brains but also increasing mRNA levels in mock‐inoculated brains with increasing age. Quantitative RT‐PCR analysis of some cholesterol‐related genes in untreated mice suggested that changes of the examined genes observed in mock‐inoculated brains are mainly age related. This finding indicated a link between age‐related genes and scrapie‐associated neurodegeneration.
Blood–brain barrier disruption induces in vivo degeneration of nigral dopaminergic neurons
Authors: Rite Inmaculada , Machado Alberto , Cano Josefina , Venero José L. 
Published: May 2007

AbstractWe have evaluated the possibility that changes in the vascular system may constitute a contributing factor for the death of nigral dopaminergic neurons in Parkinson’s disease. Thus, we have employed intranigral injections of vascular endothelial growth factor (VEGF), the most potent inducer of blood–brain barrier (BBB) permeability. A single dose of 1 μg of VEGF, chosen from a dose‐response study, highly disrupted the BBB in the ventral mesencephalon in a time‐dependent manner. A strong regional correlation between BBB disruption and loss of tyrosine hydroxylase‐positive neurons was evident. Moreover, Fluoro‐Jade B labelling showed the presence of dying neurons in the substantia nigra in response to VEGF injection. High number of TUNEL‐positive nuclei was observed in this area along with activation of caspase 3 within nigral dopaminergic neurons. Analysis of the glial population demonstrated a strong inflammatory response and activation of astroglia in response to BBB disruption. We conclude that disruption of the BBB may be a causative factor for degeneration of nigral dopaminergic neurons.
Activation of recombinant human TRPV1 receptors expressed in SH‐SY5Y human neuroblastoma cells increases [Ca2+]i, initiates neurotransmitter release and promotes delayed cell death
Authors: Lam Patricia M. W. , Hainsworth Atticus H. , Smith Graham D. , Owen Davina E. , Davies James , Lambert David G. 
Published: May 2007

AbstractThe transient receptor potential (TRP) vanilloid receptor subtype 1 (TRPV1) is a ligand‐gated, Ca2+‐permeable ion channel in the TRP superfamily of channels. We report the establishment of the first neuronal model expressing recombinant human TRPV1 (SH‐SY5YhTRPV1). SH‐SY5Y human neuroblastoma cells were stably transfected with hTRPV1 using the Amaxa Biosystem (hTRPV1 in pIREShyg2 with hygromycin selection). Capsaicin, olvanil, resiniferatoxin and the endocannabinoid anandamide increased [Ca2+]iwith potency (EC50) values of 2.9 nmol/L, 34.7 nmol/L, 0.9 nmol/L and 4.6 μmol/L, respectively. The putative endovanilloidN‐arachidonoyl‐dopamine increased [Ca2+]ibut this response did not reach a maximum. Capsaicin, anandamide, resiniferatoxin and olvanil mediated increases in [Ca2+]iwere inhibited by the TRPV1 antagonists capsazepine and iodo‐resiniferatoxin with potencies (KB) of ∼70 nmol/L and 2 nmol/L, respectively. Capsaicin stimulated the release of pre‐labelled [3H]noradrenaline from monolayers of SH‐SY5YhTRPV1cells with an EC50of 0.6 nmol/L indicating amplification between [Ca2+]iand release. In a perfusion system, we simultaneously measured [3H]noradrenaline release and [Ca2+]iand observed that increased [Ca2+]ipreceded transmitter release. Capsaicin treatment also produced a cytotoxic response (EC50155 nmol/L) that was antagonist‐sensitive and mirrored the [Ca2+]Iresponse. This model displays pharmacology consistent with TRPV1 heterologously expressed in standard non‐neuronal cells and native neuronal cultures. The advantage of SH‐SY5YhTRPV1is the ability of hTRPV1 to couple to neuronal biochemical machinery and produce large quantities of cells.
Down‐regulation of GRK2 after oxygen and glucose deprivation in rat hippocampal slices: role of the PI3‐kinase pathway
Authors: Lombardi Maria Stella , Vroon Anne , Sodaar Peter , Van Muiswinkel Freek L. , Heijnen Cobi J. , Kavelaars Annemieke 
Published: May 2007

AbstractG protein‐coupled receptor kinase 2 (GRK2) modulates G protein‐coupled receptor desensitization and signaling. We previously described down‐regulation of GRK2 expression in vivo in rat neonatal brain following hypoxia‐ischemia. In this study, we investigated the molecular mechanisms involved in GRK2 down‐regulation, using organotypic cultures of neonatal rat hippocampal slices exposed to oxygen and glucose deprivation (OGD). We observed a 40% decrease in GRK2 expression 4 h post‐OGD. No changes in GRK2 protein occurred after exposure of hippocampal slices to glucose deprivation only. No significant alterations in GRK2 mRNA expression were detected, suggesting a post‐transcriptional effect of OGD on GRK2 expression. Blockade of the proteasome pathway by MG132 prevented OGD‐induced decrease of GRK2. It has been shown that extracellular signal‐regulated kinase‐dependent phosphorylation of GRK2 at Ser670 triggers its turnover via the proteasome pathway. However, despite a significant increase of pSer670‐GRK2 after OGD, inhibition of the extracellular signal‐regulated kinase pathway by PD98059 did neither prevent the hypoxia‐ischemia‐induced increase in pSer670‐GRK2 nor the down‐regulation of GRK2 protein. Interestingly, inhibition of phosphoinositide‐3‐kinase with wortmannin inhibits both OGD‐induced phosphorylation of GRK2 on Ser670 and the GRK2 decrease. In conclusion, OGD‐induced phosphoinositide‐3‐kinase‐dependent phosphorylation of GRK2 on Ser670 is a novel mechanism leading to down‐regulation of GRK2 protein via a proteasome‐dependent pathway.
Modulation of hippocampal calcium signalling and plasticity by serine/threonine protein phosphatases
Authors: Koss David J. , Hindley Kathleen P. , Riedel Gernot , Platt Bettina 
Published: May 2007

AbstractKinases and phosphatases act antagonistically to maintain physiological phosphorylation/dephosphorylation at numerous intracellular sites critical for neuronal signalling. In this study, it was found that inhibition of serine/threonine phosphatases by exposure of hippocampal slices to okadaic acid (OA) or cantharidin (CA; 100 nmol/L) for 2 h resulted in reduced basal synaptic transmission and blocked the induction of synaptic plasticity in the form of long‐term potentiation as determined by electrophysiological analysis. Fura‐2 Ca2+ imaging revealed a bidirectional modulation of N‐methyl‐d‐aspartate (NMDA) ‐mediated Ca2+ responses and reduced KCl‐mediated Ca2+ responses in neonatal cultured hippocampal neurons after phosphatase inhibition. While OA inhibited NMDA‐induced Ca2+ influx both acutely and after incubation, CA‐enhanced receptor‐mediated Ca2+ signalling at low concentrations (1 nmol/L) but reduced NMDA and KCl‐mediated Ca2+ responses at higher concentrations (100 nmol/L). Changes in Ca2+ signalling were accompanied by increased phosphorylation of cytoskeletal proteins tau and neurofilament and the NMDA receptor subunit NR1 in selective treatments. Incubation with OA (100 nmol/L) also led to the disruption of the microtubule network. This study highlights novel signalling effects of prolonged inhibition of protein phosphatases and suggests reduced post‐synaptic signalling as a major mechanism for basal synaptic transmission and long‐term potentiation impairments.
Nidogen is a prosurvival and promigratory factor for adult Schwann cells
Authors: Lee Hyun Kyoung , Seo In Ae , Park Hye Kyung , Park Yoo Mi , Ahn Kyoung Jin , Yoo Young Hyun , Park Hwan Tae 
Published: May 2007

AbstractSchwann cells provide a favorable microenvironment for successful regeneration of the injured peripheral nerve. Even though the roles of extracellular matrix proteins in the Schwann cell physiology have long been studied, the precise function of nidogen, a ubiquitous component of the basal lamina, in Schwann cells is unknown. In this study, we show that the protein and mRNA messages for nidogens are up‐regulated in the sciatic nerve after sciatic nerve transection. We demonstrate that recombinant nidogen‐1 increased the process formation of Schwann cells cultured from adult rat sciatic nerves and that nidogen‐1 prevented Schwann cells from serum‐deprivation‐induced death. In addition, nidogen‐1 promoted spontaneous migration of Schwann cells in two‐independent migration assays. The Schwann cell responses to the recombinant nidogen‐1 were specific because the nidogen‐binding ectodomain of tumor endothelial marker 7 inhibited the nidogen responses without affecting Schwann cell response to laminin. Finally, we found that β1 subunit‐containing integrins play a key role in the nidogen‐induced process formation, survival, and migration of Schwann cells. Altogether, these results indicate that nidogen has a prosurvival and promigratory activity on Schwann cells in the peripheral nerve.
Lysophosphatidic acid rescues RhoA activation and phosphoinositides levels in astrocytes exposed to ethanol
Authors: Martínez Susana E. , Lázaro‐Diéguez Francisco , Selva Javier , Calvo Fernando , Piqueras Jaime‐Renau , Crespo Piero , Claro Enrique , Egea Gustavo 
Published: May 2007

AbstractLong‐term ethanol treatment substantially impairs glycosylation and membrane trafficking in primary cultures of rat astrocytes. Our previous studies indicated that these effects were attributable to a primary alteration in the dynamics and organization of the actin cytoskeleton, although the molecular mechanism(s) remains to be elucidated. As small Rho GTPases and phosphoinositides are involved in the actin cytoskeleton organization, we now explore the effects of chronic ethanol treatment on these pathways. We show that chronic ethanol treatment of rat astrocytes specifically reduced endogenous levels of active RhoA as a result of the increase of in the RhoGAP activity. Furthermore, ethanol‐treated astrocytes showed reduced phosphoinositides levels. When lysophosphatidic acid was added to ethanol‐treated astrocytes, it rapidly reverted actin cytoskeleton reorganization and raised active RhoA levels and phosphoinositides content to those observed in untreated astrocytes. Overall, our results indicate that the harmful effects of chronic exposure to ethanol on a variety of actin dynamics‐associated cellular events are primarily because of alterations of activated RhoA and phosphoinositides pools.
Capsaicin‐induced apoptosis of glioma cells is mediated by TRPV1 vanilloid receptor and requires p38 MAPK activation
Authors: Amantini C , Mosca M , Nabissi M , Lucciarini R , Caprodossi S , Arcella A , Giangaspero F , Santoni G 
Published: May 2007

AbstractWe provide evidence on the expression of the transient receptor potential vanilloid type‐1 (TRPV1) by glioma cells, and its involvement in capsaicin (CPS)‐induced apoptosis. TRPV1 mRNA was identified by quantitative RT‐PCR in U373, U87, FC1 and FLS glioma cells, with U373 cells showing higher, and U87, FC1 and FLS cells lower TRPV1 expression as compared with normal human astrocytes. By flow cytometry we found that a substantial portion of both normal human astrocytes, and U87 and U373 glioma cells express TRPV1 protein. Moreover, we analyzed the expression of TRPV1 at mRNA and protein levels of glioma tissues with different grades. We found that TRPV1 gene and protein expression inversely correlated with glioma grading, with marked loss of TRPV1 expression in the majority of grade IV glioblastoma multiforme. We also described that CPS trigger apoptosis of U373, but not U87 cells. CPS‐induced apoptosis involved Ca2+influx, p38 but not extracellular signal‐regulated mitogen‐activated protein kinase activation, phosphatidylserine exposure, mitochondrial permeability transmembrane pore opening and mitochondrial transmembrane potential dissipation, caspase 3 activation and oligonucleosomal DNA fragmentation. TRPV1 was functionally implicated in these events as they were markedly inhibited by the TRPV1 antagonist, capsazepine. Finally, p38 but not extracellular signal‐regulated protein kinase activation was required for TRPV1‐mediated CPS‐induced apoptosis of glioma cells.
A glycogen phosphorylase inhibitor selectively enhances local rates of glucose utilization in brain during sensory stimulation of conscious rats: implications for glycogen turnover
Authors: Dienel Gerald A. , Ball Kelly K. , Cruz Nancy F. 
Published: May 2007

AbstractGlycogen is degraded during brain activation but its role and contribution to functional energetics in normal activated brain have not been established. In the present study, glycogen utilization in brain of normal conscious rats during sensory stimulation was assessed by three approaches, change in concentration, release of 14C from pre‐labeled glycogen and compensatory increase in utilization of blood glucose (CMRglc) evoked by treatment with a glycogen phosphorylase inhibitor. Glycogen level fell in cortex, 14C release increased in three structures and inhibitor treatment caused regionally selective compensatory increases in CMRglc over and above the activation‐induced rise in vehicle‐treated rats. The compensatory rise in CMRglc was highest in sensory‐parietal cortex where it corresponded to about half of the stimulus‐induced rise in CMRglcf in vehicle‐treated rats; this response did not correlate with metabolic rate, stimulus‐induced rise in CMRglc or sequential station in sensory pathway. Thus, glycogen is an active fuel for specific structures in normal activated brain, not simply an emergency fuel depot and flux‐generated pyruvate greatly exceeded net accumulation of lactate or net consumption of glycogen during activation. The metabolic fate of glycogen is unknown, but adding glycogen to the fuel consumed during activation would contribute to a fall in CMRO2/CMRglc ratio.
Isolation and characterization of novel microsatellite loci for parentage assessment in the lance‐tailed manakin (Chiroxiphia lanceolata)
Authors: DUVAL EMILY H. , CARTER KIM L. , KEMPENAERS BART 
Published: May 2007

AbstractThe lance‐tailed manakin (Chiroxiphia lanceolata) is a lek‐breeding bird from Central America in which males court females with complex cooperative displays. To resolve detailed patterns of paternity in the wild, we isolated and characterized 12 novel microsatellite loci in this species. Eleven of these loci were polymorphic (five to 14 alleles), with observed heterozygosities ranging from 0.36 to 0.87 (N = 574 individuals). We tested for linkage disequilibrium using randomized subsamples of adults to control for known family structure among long‐lived and sedentary individuals. These loci will be valuable in resolving paternity among many candidate fathers in this species.
Lack of association between rifampicin plasma concentration and treatment‐related side effects in osteoarticular infections
Authors: Roblot France , Besnier Jean‐Marc , Giraudeau Bruno , Simonnard Nicolas , Jonville‐Bera Annie‐Pierre , Coipeau Patrick , Choutet Patrick , Autret‐Leca Elisabeth , Le Guellec Chantal 
Published: May 2007

AbstractThe aim of this study was to assess the frequency of gastrointestinal side effects (GSE) and hepatotoxicity in patients treated with rifampicin for an osteoarticular infection and to determine if there is an association between rifampicin plasma concentrations and side effects. Rifampicin plasma concentrations were prospectively measured before (trough concentration, C0) and 2 ± 0.5 h (peak concentration, C2) after drug intake. The presence of GSE, the alanine transferase (ALT) value, and concomitantly administered medications were recorded on the day rifampicin concentrations were measured. C0 and C2 were compared for differences regarding the presence or absence of side effects. Multivariate analysis was performed, with associated medications being taken into account. Seventy C0 and 57 C2 values were measured in 46 adults after a median treatment of 8 days (range, 1–179). Wide inter‐individual variability was observed for C0 and C2. Thirteen (28%) patients reported GSE at least once. When GSE occurred, C0 (median, 1 mg L−1; range, 0.1–9.9 mg L−1) and C2 (median, 10.3 mg L−1; range, 1.8–40.3 mg L−1) were similar to C0 (median, 0.6 mg L−1; range, 0.1–10.3 mg L−1) and C2 (median, 10.9 mg L−1; range, 2.9–29.0 mg L−1) without GSE. The ALT value was more than normal in only three patients (6.5%) after rifampicin treatment began. The patients received no different associated medications whether or not GSE were present. Multivariate analysis showed no association between rifampicin plasma concentrations and GSE. GSE occur frequently in patients receiving rifampicin for osteoarticular infection but without an association with rifampicin plasma concentrations. Thus, therapeutic drug monitoring of rifampicin is irrelevant in the management of GSE.
Basic Science and Dialysis: Disturbances of Acquired Immunity in Hemodialysis Patients
Authors: Eleftheriadis Theodoros , Antoniadi Georgia , Liakopoulos Vassilios , Kartsios Charalambos , Stefanidis Ioannis 
Published: May 2007

AbstractAcquired immunity disturbances in hemodialysis (HD) patients are many and diverse. They are caused by uremia per se, the HD procedure, chronic renal failure complications, and therapeutic interventions for their treatment. Current data suggest that acquired immunity disturbances in HD patients concern mainly the T‐lymphocyte and the antigen‐presenting cell (APC). The T‐lymphocyte‐dependent immune response is deficient, predisposing to infections and inadequate response to vaccinations. In addition, APCs are preactivated, which seems to be responsible for the malnutrition–inflammation–atherosclerosis syndrome, and also affects T‐lymphocyte function. At the molecular level it is assumed that the interaction between the APC and the T‐lymphocyte is impaired. This disturbance is likely to concern the signal that results from the interaction between the major histocompatibility complex:peptide complex on APC surfaces and T‐cell receptors on T‐lymphocyte surfaces, or the signal that results from the interaction among the co‐receptors of these two cells. The aim of the present review was to collect and classify the available clinical and experimental data in this area. Although many pieces are still missing from the puzzle, a better understanding of the responsible molecular mechanisms, will potentially lead to increased survival and a better quality of life in HD patients.
Effect of three different dental health preventive programmes on young adult individuals: a randomized, blinded, parallel group, controlled evaluation of oral hygiene behaviour on plaque and gingivitis
Authors: Hugoson Anders , Lundgren Dan , Asklöw Barbro , Borgklint Gun 
Published: May 2007

AbstractAim:To evaluate, in young adults, the effect of different preventive programmes on oral hygiene and to determine whether the variables investigated are predictors of gingival health.Material and Methods:This randomized, blinded, parallel, controlled clinical study examined the effectiveness of three dental health programmes. Four hundred subjects aged 20–27 years, 211 males and 189 females, participated in the study. They were recruited from a Public Dental Service clinic and from a private dental practice in Jönköping, Sweden. The effect of the programmes on plaque and gingivitis was evaluated over a 3‐year period. The programmes included activities that were adapted for individuals as well as for groups. The plaque indices (PLI) and gingival indices (GI) were used to evaluate the programmes.Results:All programmes resulted in a decrease in PLI and GI. The greatest decrease was found in the group that was followed‐up every 2 months. Professional tooth cleaning was non‐significant for the clinical result. Gingival health at baseline, participation in any of the test programmes, and knowledge of the dental diseases caries, gingivitis or periodontitis were significant predictors of good gingival health.Conclusions:The study confirms the efficacy of three different preventive programmes in reducing supragingival plaque and gingival inflammation. Professional tooth cleaning provided no clinical benefit beyond that derived from individual and group‐based health education.
Gingival blood flow changes following periodontal access flap surgery using laser Doppler flowmetry
Authors: Retzepi M. , Tonetti M. , Donos N. 
Published: May 2007

AbstractAim: To investigate the pattern of gingival blood flow changes following periodontal access flap surgery by laser Doppler flowmetry (LDF).Material and methods: Fourteen patients with chronic periodontitis presenting upper anterior sites with pocket depth 5 mm after initial treatment were included in the study. Periodontal access flap surgery was performed on the experimental areas and LDF recordings were taken at baseline, following anaesthesia, immediately postoperatively and on days 1, 2, 3, 4, 7, 15, 30 and 60 of healing, at nine predetermined sites per flap.Results: Significant ischaemia was observed at all flap sites following anaesthesia and immediately postoperatively. At the alveolar mucosal sites, a peak increase of the gingival blood flow was observed on postoperative day 1 (p<0.001), which persisted until day 7 (p=0.012) and resolved by day 15. The mucosal sites close to the flap periphery presented higher blood perfusion compared with the sites located centrally in the flap. The microcirculatory perfusion of the buccal and palatal papillae was maximum on postoperative day 7 (p=0.013 and <0.001, respectively) and returned to baseline by day 15.Conclusion: Topographically distinct areas of the periodontal access flap consistently present different patterns of microvascular blood flow alterations during the wound‐healing period.