bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholesterol asymmetry in synaptic plasma membranes
Authors: Gibson Wood W. , Igbavboa Urule , Müller Walter E. , Eckert Gunter P. 
Published: January 2011

J. Neurochem.(2011)116, 684–689.AbstractLipids are essential for the structural and functional integrity of membranes. Membrane lipids are not randomly distributed but are localized in different domains. A common characteristic of these membrane domains is their association with cholesterol. Lipid rafts and caveolae are examples of cholesterol enriched domains, which have attracted keen interest. However, two other important cholesterol domains are the exofacial and cytofacial leaflets of the plasma membrane. The two leaflets that make up the bilayer differ in their fluidity, electrical charge, lipid distribution, and active sites of certain proteins. The synaptic plasma membrane (SPM) cytofacial leaflet contains over 85% of the total SPM cholesterol as compared with the exofacial leaflet. This asymmetric distribution of cholesterol is not fixed or immobile but can be modified by different conditionsin vivo: (i) chronic ethanol consumption; (ii) statins; (iii) aging; and (iv) apoE isoform. Several potential candidates have been proposed as mechanisms involved in regulation of SPM cholesterol asymmetry: apoE, low‐density lipoprotein receptor, sterol carrier protein‐2, fatty acid binding proteins, polyunsaturated fatty acids, P‐glycoprotein and caveolin‐1. This review examines cholesterol asymmetry in SPM, potential mechanisms of regulation and impact on membrane structure and function.
Roles of sphingolipids in Drosophila development and disease
Authors: Kraut Rachel 
Published: January 2011

J. Neurochem. (2011) 116, 764–778.AbstractThe last 10 years have seen a rebirth of interest in lipid biology in the fields of Drosophila development and neurobiology, and sphingolipids have emerged as controlling many processes that have not previously been studied from the viewpoint of lipid biochemistry. Mutations in sphingolipid regulatory enzymes have been pinpointed as affecting cell survival and growth in tissues ranging from muscle to retina. Specification of cell types are also influenced by sphingolipid regulatory pathways, as genetic interactions of glycosphingolipid biosynthetic enzymes with many well‐known signaling receptors such as Notch and epidermal growth factor receptor reveal. Furthermore, studies in flies are now uncovering unexpected roles of sphingolipids in controlling lipid storage and response to nutrient availability. The sophisticated genetics of Drosophila is particularly well suited to uncover the roles of sphingolipid regulatory enzymes in development and metabolism, especially in light of conserved pathways that are present in both flies and mammals. The challenges that remain in the field of sphingolipid biology in Drosophila are to combine traditional developmental genetics with more analytical biochemical and biophysical methods, to quantify and localize the responses of these lipids to genetic and metabolic perturbations.
Purinergic signalling at the plasma membrane: a multipurpose and multidirectional mode to deal with amyotrophic lateral sclerosis and multiple sclerosis
Authors: Amadio Susanna , Apolloni Savina , D’Ambrosi Nadia , Volonté Cinzia 
Published: January 2011

J. Neurochem. (2011) 116, 796–805.AbstractATP is a widespread and multipurpose signalling molecule copiously released in the extracellular environment of the whole nervous system upon cell activation, stress, or damage. Extracellular ATP is also a multidirectional information molecule, given the concurrent presence at the plasma membrane of various targets for ATP. These include ectonucleotidases (metabolizing ATP down to adenosine), ATP/adenosine transporters, P2 receptors for purine/pyrimidine nucleotides (ligand‐gated ion channels P2X receptors and G‐protein‐coupled P2Y receptors), in addition to metabotropic P1 receptors for nucleosides. All these targets rarely operate as single units, rather they associate with each other at the plasma membrane as multi‐protein complexes. Altogether, they control the duration, magnitude and/or direction of the signals triggered and propagated by purine/pyrimidine ligands, and the impact that each single ligand has on a variety of short‐ and long‐term functions. A strict control system allows assorted, even divergent, biological outcomes. Among these, we enumerate cell‐to‐cell communication, tropic, trophic, but also noxious actions causing the insurgence/progression of pathological conditions. Here, we show that purinergic signalling in the nervous system can be instrumental for instance to neurodegenerative and neuroinflammatory diseases such as amyotrophic lateral sclerosis and multiple sclerosis.
Cannabinoid 1 receptor‐dependent transactivation of fibroblast growth factor receptor 1 emanates from lipid rafts and amplifies extracellular signal‐regulated kinase 1/2 activation in embryonic cortical neurons
Authors: Asimaki Olga , Leondaritis George , Lois Giannis , Sakellaridis Nikos , Mangoura Dimitra 
Published: January 2011

J. Neurochem. (2011) 116, 866–873.AbstractG‐protein coupled receptors may mediate their effects on neuronal growth and differentiation through activation of extracellular signal‐regulated kinases 1/2 (ERK1/2), often elicited by transactivation of growth factor receptor tyrosine kinases. This elaborate signaling process includes inducible formation and trafficking of multiprotein signaling complexes and is facilitated by pre‐ordained membrane microdomains, in particular lipid rafts. In this study, we have uncovered novel signaling interactions of cannabinoid receptors with fibroblast growth factor receptors, which depended on lipid rafts and led to ERK1/2 activation in primary neurons derived from chick embryo telencephalon. More specifically, the cannabinoid 1 receptor (CB1R) agonist methanandamide induced tyrosine phosphorylation and transactivation of fibroblast growth factor receptor (FGFR)1 via Src and Fyn, which drove an amplification wave in ERK1/2 activation. Transactivation of FGFR1 was accompanied by the formation of a protein kinase C ε‐dependent multiprotein complex that included CB1R, Fyn, Src, and FGFR1. Recruitment of molecules increased with time of exposure to methanandamide, suggesting that in addition to signaling it also served trafficking of receptors. Upon agonist stimulation we also detected a rapid incorporation of CB1R, as well as activated Src and Fyn, and FGFR1 in lipid rafts. Most importantly, lipid raft integrity was a pre‐requisite for CB1R‐dependent complex formation. Our data provide evidence that lipid rafts may organize CB1 receptor proximal signaling events, namely activation of Src and Fyn, and transactivation of FGFR1 towards activation of ERK1/2 and induction of neuronal differentiation.
Functional characterization of putative cholesterol binding sequence (CRAC) in human type‐1 cannabinoid receptor
Authors: Oddi Sergio , Dainese Enrico , Fezza Filomena , Lanuti Mirko , Barcaroli Daniela , De Laurenzi Vincenzo , Centonze Diego , Maccarrone Mauro 
Published: January 2011

J. Neurochem. (2011) 116, 858–865.AbstractEndocannabinoid signaling modulates a variety of neuroinflammatory and neurodegenerative diseases, mainly through the activation of type‐1 and type‐2 (CB1R and CB2R) cannabinoid receptors. CB1R is negatively regulated by membrane cholesterol, while CB2R is unaffected. Here, we identified in the transmembrane helix 7 of human CBRs a consensus sequence already known in other proteins as cholesterol recognition/interaction amino acid sequence and consensus pattern. As this motif is different in the two CBR subtypes, we mutated lysine 402 of CB1R into glycine, to obtain a cholesterol recognition/interaction amino acid sequence and consensus similar to that of CB2R. Both mutated and wild‐type receptors were transiently expressed in human neuronal SH‐SY5Y cells, and their localization and functioning were investigated using biochemical assays and immunofluorescence labelling. We found a reduced propensity of the mutant CB1R to reside in cholesterol‐rich microdomains and, by means of fluorescence recovery after photobleaching analysis, we documented its loss of sensitivity to increased membrane cholesterol content. These results seem to uncover the existence of a new structural determinant in cannabinoid receptors, that is likely implicated in directing their interaction with cholesterol‐rich microdomains of cell membranes.
Histone acetylation‐mediated glycosyltransferase gene regulation in mouse brain during development
Authors: Suzuki Yusuke , Yanagisawa Makoto , Ariga Toshio , Yu Robert K. 
Published: January 2011

J. Neurochem. (2011) 116, 874–880.AbstractGangliosides are sialic acid‐containing glycosphingolipids abundant in the central nervous tissues. The quantity and expression pattern of gangliosides in brain change drastically during early development and are mainly regulated through stage‐specific expression of glycosyltransferase (ganglioside synthase) genes. It is still unclear, however, how the transcriptional activation of glycosyltransferase genes is regulated during development. In this study, we investigated the epigenetic regulation of two key glycosyltransferases, N‐acetylgalactosaminyltransferase I (GA2/GM2/GD2/GT2‐synthase) and sialyltransferase II (GD3‐synthase), in embryonic, postnatal, and adult mouse brains. Combined bisulfite restriction analysis assay showed that DNA methylation in the 5′ regions of these glycosyltransferase genes was not associated with their expression patterns. On the other hand, chromatin immunoprecipitation assay of both glycosyltransferase genes showed that their histone H3 acetylation was highly correlated to their mRNA expression levels during development. In fact, we confirmed that the expression patterns of gangliosides and glycosyltransferases in neuroepithelial cells were changed after treatment with a histone deacetylase inhibitor, sodium butyrate. Our studies provide the first evidence that efficient histone acetylation of the glycosyltransferase genes in mouse brain contributes to the developmental alteration of ganglioside expression.
Myelin‐associated glycoprotein protects neurons from excitotoxicity
Authors: Lopez Pablo H. H. , Ahmad Abdullah S. , Mehta Niraj R. , Toner Mayu , Rowland Elizabeth A. , Zhang Jiangyang , Doré Sylvain , Schnaar Ronald L. 
Published: January 2011

J. Neurochem. (2011) 116, 900–908.AbstractIn addition to supporting rapid nerve conduction, myelination nurtures and stabilizes axons and protects them from acute toxic insults. One myelin molecule that protects and sustains axons is myelin‐associated glycoprotein (MAG). MAG is expressed on the innermost wrap of myelin, apposed to the axon surface, where it interacts with axonal receptors that reside in lateral membrane domains including gangliosides, the glycosylphosphatidylinositol‐anchored Nogo receptors, and β1‐integrin. We report here that MAG protection extends beyond the axon to the neurons from which those axons emanate, protecting them from excitotoxicity. Compared to wild type mice, Mag‐null mice displayed markedly increased seizure activity in response to intraperitoneal injection of kainic acid, an excitotoxic glutamate receptor agonist. Mag‐null mice also had larger lesion volumes in response to intrastriatal injection of the excitotoxin NMDA. Prior injection of a soluble form of MAG partially protected Mag‐null mice from NMDA‐induced lesions. Hippocampal neurons plated on proteins extracted from wild‐type rat or mouse myelin were resistant to kainic acid‐induced excitotoxicity, whereas neurons plated on proteins from Mag‐null myelin were not. Protection was reversed by anti‐MAG antibody and replicated by addition of soluble MAG. MAG‐mediated protection from excitotoxicity was dependent on Nogo receptors and β1‐integrin. We conclude that MAG engages membrane‐domain resident neuronal receptors to protect neurons from excitotoxicity, and that soluble MAG mitigates excitotoxic damage in vivo.
Plasmalogen synthesis is regulated via alkyl‐dihydroxyacetonephosphate‐synthase by amyloid precursor protein processing and is affected in Alzheimer’s disease
Authors: Grimm Marcus O. W. , Kuchenbecker Johanna , Rothhaar Tatjana L. , Grösgen Sven , Hundsdörfer Benjamin , Burg Verena K. , Friess Petra , Müller Ulrike , Grimm Heike S. , Riemenschneider Mathias , Hartmann Tobias 
Published: January 2011

J. Neurochem. (2011) 116, 916–925.AbstractLipids play an important role as risk or protective factors in Alzheimer’s disease, which is characterized by amyloid plaques composed of aggregated amyloid‐beta. Plasmalogens are major brain lipids and controversially discussed to be altered in Alzheimer’s disease (AD) and whether changes in plasmalogens are cause or consequence of AD pathology. Here, we reveal a new physiological function of the amyloid precursor protein (APP) in plasmalogen metabolism. The APP intracellular domain was found in vivo and in vitro to increase the expression of the alkyl‐dihydroxyacetonephosphate‐synthase (AGPS), a rate limiting enzyme in plasmalogen synthesis. Alterations in APP dependent changes of AGPS expression result in reduced protein and plasmalogen levels. Under the pathological situation of AD, increased amyloid‐beta level lead to increased reactive oxidative species production, reduced AGPS protein and plasmalogen level. Accordingly, phosphatidylethanol plasmalogen was decreased in the frontal cortex of AD compared to age matched controls. Our findings elucidate that plasmalogens are decreased as a consequence of AD and regulated by APP processing under physiological conditions.
Ganglioside GD3 monoclonal antibody‐induced paxillin tyrosine phosphorylation and filamentous actin assembly in cerebellar growth cones
Authors: Yuyama Kohei , Sekino‐Suzuki Naoko , Yamamoto Naomasa , Kasahara Kohji 
Published: January 2011

J. Neurochem. (2011) 116, 845–850.AbstractWe have demonstrated that antibody to ganglioside GD3 (R24) immunoprecipitates src‐family tyrosine kinase Lyn from primary cerebellar granule cells and R24 treatment of the intact cells induces Lyn activation and rapid tyrosine phosphorylation of several substrates, suggesting the functional association of ganglioside GD3 with Lyn. In this study, R24 treatment of primary cerebellar granule cells enhances phosphorylation of paxillin at tyrosine residue 118 and induces filamentous actin assembly and neurite outgrowth. R24 treatment of cerebellar growth cone membrane fraction induces prominent tyrosine phosphorylation of 68 kDa protein which comigrates with phosphopaxillin at tyrosine residue 118. Tyrosine phosphorylation of paxillin is known to regulate actin cytoskeleton‐dependent changes in cell morphology. Signal transduction by ganglioside GD3 is involved in growth cone morphology via tyrosine phosphorylation of paxillin.
Regulation of tyrosine kinase B activity by the Cyp46/cholesterol loss pathway in mature hippocampal neurons: relevance for neuronal survival under stress and in aging
Authors: Sodero Alejandro O. , Trovò Laura , Iannilli Francesca , Van Veldhoven Paul , Dotti Carlos G. , Martin Mauricio G. 
Published: January 2011

J. Neurochem. (2011) 116, 747–755.AbstractIt is well established that memory formation and retention involve the coordinated flow of information from the post‐synaptic site of particular neuronal populations to the nucleus, where short and long‐lasting modifications of gene expression occur. With age, mnemonic, motor and sensorial alterations occur, and it is believed that extra failures in the mechanisms used for memory formation and storage are the cause of neurodegenerative pathologies like Alzheimer’s disease. A prime candidate responsible for damage and loss of function during aging is the accumulation of reactive oxygen species, derived from normal oxidative metabolism. However, dysfunction in the aged brain is not paralleled by an increase in neuronal death, indicative that the brain is better suited to fight against the death signals generated from reactive oxygen species than against loss‐of‐function stimuli. A main aim of this laboratory is to understand how neurons perform and survive in the constitutive stress background represented by aging. In this report, we summarize our recent findings in relation to survival.
Assessment of abuse of tianeptine from a reimbursement database using ‘doctor‐shopping’ as an indicator
Authors: Rouby Frank , Pradel Vincent , Frauger Elisabeth , Pauly Vanessa , Natali François , Reggio Patrick , Thirion Xavier , Micallef Joëlle 
Published: January 2011

AbstractDoctor‐shopping is a patient behaviour characterized by simultaneous consultations of several physicians during the same period. Some case reports have described an abuse of tianeptine, an atypical antidepressant. Our objective was to assess the extent of abuse of this drug with a method quantifying doctor‐shopping in comparison with other antidepressants and benzodiazepines (BZD). All dispensations of antidepressants and BZD during the year 2005 in a French area of 4.5 million inhabitants were extracted from a reimbursement database. For each patient, two quantities were computed: quantity dispensed and obtained by doctor‐shopping. Tianeptine and other drugs were compared using their doctor‐shopping indicator (DSI), defined as the percentage of drug obtained by doctor‐shopping among dispensed quantity; 410 525 patients received at least one antidepressant dispensation during the year 2005. Tianeptine was the sixth most dispensed antidepressant. The DSI of tianeptine was 2.0%, ranking it first among antidepressant (the second being mianserine with a DSI of 1%). Flunitrazepam has the highest DSI (30.2%), the DSI of the five following BZD (clonazepam, zolpidem, oxazepam, diazepam, bromazepam) range from 3.0% to 2.0%. Tianeptine is associated with higher DSI, compared with other antidepressants, suggesting that it may be subject to abuse in the population. Moreover, its DSI as a measure of diversion is similar to the DSI of diazepam or bromazepam.
Protective effect of antioxidants on blood oxidative stress caused by arginine
Authors: de Lima Daniela Delwing , Delwing Fábio , da Cruz José Geraldo Pereira , Wyse Angela Terezinha Souza , Magro Débora Delwing‐Dal 
Published: January 2011

AbstractIn this study, we investigated in vivo and in vitro effect of arginine on parameters of oxidative stress namely thiobarbituric acid‐reactive substances (TBA‐RS) and total radical‐trapping antioxidant parameter (TRAP) in plasma and on the antioxidant enzymes activities catalase (CAT), glutathione peroxidase (GSH‐Px), and superoxide dismutase (SOD) in erythrocytes of rats. Results showed that acute administration reduced TRAP and CAT activity and increased TBA‐RS. Furthermore, in vitro studies did not alter oxidative parameters studied. The influence of Nω‐nitro‐l‐arginine methyl ester (l‐NAME) and antioxidants (α‐tocopherol plus ascorbic acid) on the effects elicited by arginine was also studied. In addition, simultaneous injection of l‐NAME or treatment with antioxidants prevented the alteration on TRAP, TBA‐RS, and CAT activity caused by arginine. Data indicate that oxidative stress induction is probably mediated by the generation of NO and/or ONOO− and other free radicals, because l‐NAME and these antioxidants prevented these effects caused by arginine.
Diverse modulating effects of estradiol and progesterone on the monophasic action potential duration in Langendorff‐perfused female rabbit hearts
Authors: Cheng Jianhua , Ma Xiaohong , Zhang Juan , Su Dan 
Published: January 2011

AbstractThis study aimed to comparatively investigate the acute modulating effects of oestrogen and progesterone on the repolarization and the susceptibility of female rabbits to class III anti‐arrhythmic agents. The acute influence of estradiol and progesterone on the cardiac repolarization and the drug sensitivity of the rapidly activating delayed rectifier K+channel to sotalol was comparatively studied in Langendorff‐perfused rabbit hearts at pharmacological concentrations through recording of epicardial monophasic action potentials. In Langendorff‐perfused rabbit hearts, estradiol (1–30 μm) concentration‐dependently prolonged the monophasic action potential durations (MAPD30and MAPD90) (P < 0.05); while the effects of progesterone on MAPD were biphasic: it prolonged MAPD30and MAPD90at lower concentrations (1–3 μm) but shortened MAPD30and MAPD90at higher concentrations (10–30 μm). Sotalol‐induced prolongation of MAPD90was significantly less in the hearts pretreated with progesterone than those treated with estradiol (P < 0.05). The incidence of the pro‐arrhythmic events induced by sotalol in the hearts pretreated with progesterone was also significantly lower than those pretreated with estradiol (P < 0.05). In conclusion, estradiol and progesterone have different modulating effects on cardiac repolarization: estradiol can concentration‐dependently prolong the cardiac repolarization time and thus may reduce the repolarization reserve and increase the susceptibility of female rabbits to sotalol‐induced arrhythmias, whereas progesterone may shorten the cardiac repolarization time at concentrations above 10 μm, thus protecting the heart from drug‐induced arrhythmias.
Vascular BDNF expression and oxidative stress during aging and the development of chronic hypertension
Authors: Amoureux Sébastien , Lorgis Luc , Sicard Pierre , Girard Claude , Rochette Luc , Vergely Catherine 
Published: January 2011

AbstractBrain‐derived neurotrophic factor (BDNF) and TrK receptors play an important role in vascular development and response to injury. In this study, we investigated the participation of the BDNF/TrK pathway and oxidative stress during the development of hypertension in spontaneously hypertensive rats (SHR). In SHR and normotensive rats (WKY) at 6 and 13 weeks of age, we studied (i) plasma antioxidant capacity, (ii) production of superoxide and NAD(P)H oxidase activity in aorta (iii) plasma BDNF and vascular expression of BDNF, TrKB, NAD(P)H oxidase subunits, AT1 receptor, and MCP‐1. In 6‐ and 13‐week‐old SHR aorta, superoxide level was twice than in WKY aorta. At 13 weeks, when blood pressure in SHR was 60 mmHg higher in SHR than in WKY, an enhancement of NAD(P)H oxidase activity in SHR was associated with an increase in p47phox, AT1, and BDNF expression in vessels. MCP‐1 expression increased with blood pressure. Our study demonstrated that in SHR rats, an increase in levels of vascular oxidative stress and in aortic BDNF and TrKB expression occurs prior to the rise in blood pressure, while a reinforcement of vascular and circulating oxidative stress markers is brought about later by hypertension.