bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and characterization of novel activity‐dependent transcription factors in rat cortical neurons
Authors: Sun Woong , Choi Sang‐Hyun , Park Soon Kwon , Kim Soon Jung , Noh Mi Ra , Kim Eun Hae , Kim Hyun Ju , Kim Hyun 
Published: November 2006

AbstractUsing gene chip analyses, we have identified novel neuronal activity‐dependent genes. Application of 25 mm KCl to mature (14‐day culture) rat cortical neurons resulted in more than 1.5‐fold induction of 19 genes and reduction of 42 genes among 1200 neural genes. Changes in the overall gene expression profiles appeared to be related to the reduction of excitability and induction of cellular survival signals. Among the genes identified, three transcriptional modulators [encoding Cbp/p300‐interacting transactivator with ED‐rich tail 2 (CITED2), CCAAT/enhancer binding protein β (C/EBPβ) and neuronal orphan receptor‐1, (NOR1)] were newly identified as activity‐dependent transcription factors, and two of these (CITED2 and NOR1) were found to be influenced by electroconvulsive shock (ECS). NOR1 was induced in specific brain regions by behavioral activation, such as exposure to a novel environment. Because the brain regions that exhibited the induction of these newly identified neuronal activity‐dependent transcriptional modulators were distinct from those showing the induction of previously identified activity‐dependent genes such as c‐fos, these genes might be useful markers for mapping neuronal activity in vivo.
Phosphorylation by extracellular signal‐regulated kinase of a multidomain adaptor protein, vinexin, at synapses
Authors: Ito Hidenori , Usuda Nobuteru , Atsuzawa Kimie , Iwamoto Ikuko , Sudo Kaori , Katoh‐Semba Ritsuko , Mizutani Kosuke , Morishita Rika , Deguchi Takashi , Nozawa Yoshinori , Asano Tomiko , Nagata Koh‐ichi 
Published: November 2006

AbstractVinexin is an adaptor protein that is supposed to play pivotal roles in cell adhesion, cytoskeletal organization and signaling. At least three splice variants, vinexinα, β and γ, have so far been reported. In spite of the possible importance of vinexin, the properties and functions of vinexin in neuronal cells are almost unknown. Here we show that vinexin isoforms are expressed in rat brain in a developmental stage‐dependent manner, and that vinexinα is relatively abundant in the telencephalon regions of the adult rat brain. An immunohistochemical study showed the localization of vinexinα in neurons and glia in the rat brain. In primary cultured rat hippocampal neurons, vinexin was found to be present at synapses and filopodia in growth cones by immunofluorescent analyses. Biochemical fractionation revealed the distribution of vinexin in synaptosomes. Nerve terminal localization of vinexin was confirmed by electron microscopy. Vinexinβ is reported to be phosphorylated by extracellular signal‐regulated kinase (ERK) at Ser189, which is equivalent to Ser593 of vinexinα. We thus constructed a site‐ and phosphorylation state‐specific antibody to monitor the ERK‐mediated phosphorylation of vinexin. In immunofluorescent analyses, the phosphorylation was observed at synapses formed among cultured rat hippocampal neurons and it was reduced by treatment of the cells with PD98059. In an immunoelectron microscopic examination, the phosphorylation signal was mainly detected on the postsynaptic side of synapses in the rat hippocampal neurons. As active ERK was co‐localized with vinexin in synapses, the ERK signal is likely to be involved in the regulation of vinexin‐dependent cellular processes in synapses. On the other hand, the phosphorylation was hardly detected in neurons cultured for 3 days, suggesting the presence of a yet unidentified regulatory mechanism of vinexin at the growth cone.
Striatal susceptibility to a dopaminergic neurotoxin is independent of sex hormone effects on cell survival and DAT expression but is exacerbated by central aromatase inhibition
Authors: McArthur Simon , Murray Hilary E. , Dhankot Alihusein , Dexter David T. , Gillies Glenda E. 
Published: November 2006

AbstractThe aim of this study was to investigate further the hormone‐dependent processes underlying sex differences in neurotoxic responses within the rat nigrostriatal dopaminergic (NSDA) pathway after partial lesioning with 6‐OHDA, a state thought to mimic the early stages of Parkinson's disease where, in humans and animal models alike, males appear to be more susceptible. Contrary to our hypotheses, hormone manipulations (gonadectomy ± oestrogen or androgen treatment) failed to alter survival of tyrosine hydroxylase immunoreactive cells in the substantia nigra pars compacta (SNc) after lesioning; this indicates that, unlike inherent sex differences in toxin‐induced striatal dopamine depletion, sex differences in cell loss were not hormonally generated, and that hormone‐dependent changes in dopamine depletion can occur independently of cell survival. In addition, hormonally induced changes in striatal expression of the dopamine transporter (DAT), an important factor for 6‐OHDA toxicity, did not correlate with hormonal influences on striatal dopamine loss and, in males, central inhibition of aromatase prior to 6‐OHDA infusion exacerbated striatal dopamine loss with no effect on SNc tyrosine hydroxylase‐immunoreactive survival, suggesting locally generated oestrogen is neuroprotective. These results support the novel view that sex steroid hormones produced peripherally and centrally play a significant, sex‐specific role within the sexually dimorphic NSDA pathway to modulate plastic, compensatory responses aimed at restoring striatal dopamine functionality, without affecting cell loss.
Melatonin prevents glutamate‐induced oxytosis in the HT22 mouse hippocampal cell line through an antioxidant effect specifically targeting mitochondria
Authors: Herrera Federico , Martin Vanesa , García‐Santos Guillermo , Rodriguez‐Blanco Jezabel , Antolín Isaac , Rodriguez Carmen 
Published: November 2006

AbstractThe pineal hormone melatonin has neuroprotective effects in a large number of models of neurodegeneration. Melatonin crosses the blood–brain barrier, shows a decrease in its nocturnal peaks in blood with age that has been associated with the development of neurodegenerative disorders, and has been shown to be harmless at high concentrations. These properties make melatonin a potential therapeutic agent against neurodegenerative disorders but the pathways involved in such neuroprotective effects remain unknown. In the present report we study the intracellular pathways implicated in the complete neuroprotection provided by melatonin against glutamate‐induced oxytosis in the HT22 mouse hippocampal cell line. Our results strongly suggest that melatonin prevents oxytosis through a direct antioxidant effect specifically targeted at the mitochondria. Firstly, none of the described transducers of melatonin signalling seems to be implicated in the neuroprotection provided by this indole. Secondly, melatonin does not prevent cytosolic GSH depletion‐dependent increase in reactive oxygen species (ROS), but it totally prevents mitochondrial ROS production despite the fact that the latter is much higher than the former. And finally, there is a high correlation between the concentration at which melatonin and closely related indoles exert a direct antioxidant effect in vitro and a neuroprotective effect against glutamate‐induced oxytosis.
Expression and evolution of the mammalian brain gene Ttyh1
Authors: Matthews Clayton A. , Shaw John E. , Hooper Jane A. , Young Ian G. , Crouch Michael F. , Campbell Hugh D. 
Published: November 2006

AbstractHomologues of the Drosophila melanogaster tweety (tty) gene are present in mammals and Caenorhabditis elegans. The encoded proteins have five predicted membrane‐spanning regions and recent findings suggest that some family members may be chloride channels. Phylogenetic analysis of the tty family including novel members from slime mould Entamoeba and plants has revealed the occurrence of independent gene duplication events in different lineages. expressed sequence tag data indicate that expression of the mammalian Ttyh1 gene is restricted mainly to neural tissue and is up‐regulated in astrocytoma, glioma and several other cancers. In this study, mammalian expression vectors were used to investigate the subcellular localization and the effect of over‐expression of Ttyh1 in human epithelial kidney cells. The results confirm that Ttyh1 is a membrane protein and show that it is deposited on the substratum along the migration paths of motile cells above the α5β1‐integrin complex. The ectopic expression of Ttyh1 also induced long filopodia, which were branched and dynamic in both stationary and migratory cells. The filopodia contained F‐actin and occurred at the ends of microtubules which were polarized towards the membrane. Upon contact with nearby cells some filopodia stabilized and filled with F‐actin, whereas Ttyh1 was highly concentrated at the cell–cell interface. Ttyh1 N‐ and C‐terminal antipeptide antibodies detected Ttyh1 along the axons of neurones in primary rat hippocampal cell cultures, and in situ in whole rat brain slices around the hippocampus and occasionally between cells. These data suggest a role for Ttyh1 in process formation, cell adhesion and possibly as a transmembrane receptor.
24S‐hydroxycholesterol induces cholesterol release from choroid plexus epithelial cells in an apical‐ and apoE isoform‐dependent manner concomitantly with the induction of ABCA1 and ABCG1 expression
Authors: Fujiyoshi Masachika , Ohtsuki Sumio , Hori Satoko , Tachikawa Masanori , Terasaki Tetsuya 
Published: November 2006

AbstractThe release of cholesterol from choroid plexus epithelial cells (CPE) plays an important role in cholesterol homeostasis in the CSF. The purpose of this study was to clarify the molecules involved in cholesterol release in CPE and the regulation mechanisms of the cholesterol release by the liver X receptor (LXR) using a conditionally immortalized CPE line (TR‐CSFB3). The mRNA expression of LXRα, LXRβ and their target genes, ATP‐binding cassette transporter (ABC)A1, ABCG1, ABCG4 and ABCG5, were detected in rat choroid plexus. ABCA1 and ABCG1 protein were detected in the plasma membrane of TR‐CSFB3 cells. Following treatment with 24S‐hydroxycholesterol, an endogenous LXR ligand, the expression of ABCA1 and ABCG1 were induced in TR‐CSFB3 cells. Moreover, apolipoprotein (apo)AI‐ and high‐density lipoprotein (HDL)‐mediated cholesterol release to the apical side of TR‐CSFB3 cells was facilitated by this treatment, whereas that to the basal side was not affected. Following 24S‐hydroxycholesterol treatment, apoE3‐dependent cholesterol release from TR‐CSFB3 cells was enhanced more than the apoE4‐dependent release. These results suggest that LXR activation facilitates cholesterol release into the CSF from CPE through the functional induction of ABCA1 and ABCG1. The difference between apoE3 and apoE4 suggests that the cholesterol release from CPE is related to the development of neurodegenerative diseases.
Dopamine and adult neurogenesis
Authors: Borta Andreas , Höglinger Günter U 
Published: November 2006

AbstractDopamine is an important neurotransmitter implicated in the regulation of mood, motivation and movement. We have reviewed here recent data suggesting that dopamine, in addition to being a neurotransmitter, also plays a role in the regulation of endogenous neurogenesis in the adult mammalian brain. In addition, we approach a highly controversial question: can the adult human brain use neurogenesis to replace the dopaminergic neurones in the substantia nigra that are lost in Parkinson's disease?
NO‐cGMP mediated galanin expression in NGF‐deprived or axotomized sensory neurons
Authors: Thippeswamy Thimmasettappa , Haddley Kate , Corness Jacquie D. , Howard Mark R. , McKay Jennifer S. , Beaucourt Stephanie M. , Pope Marion D. , Murphy David , Morris Richard , Hökfelt Tomas , Quinn John P. 
Published: November 2006

AbstractLeukaemia inhibitory factor (LIF) and nerve growth factor (NGF) are well characterized regulators of galanin expression. However, LIF knockout mice containing the rat galanin 5′ proximal promoter fragment (− 2546 to + 15 bp) driving luciferase responded to axotomy in the same way as control mice. Also, LIF had no effect on reporter gene expression in vitro, neither in the presence or absence of NGF, suggesting that other factors mediate an axotomy response from the galanin promoter. We then addressed the role of nitric oxide (NO) using NGF‐deprived rat dorsal root ganglion (DRG) neuron cultures infected with viral vectors containing the above‐mentioned construct, and also studied endogenous galanin expression in axotomized DRG in vivo. Blocking endogenous NO in NGF‐deprived DRG cultures suppressed galanin promoter activity. Consistent with this, axotomized/NGF‐deprived DRG neurons expressed high levels of neuronal NO synthase (nNOS) and galanin. Further, using pharmacological NOS blockers, or adenoviral vectors expressing dominant‐negative either for nNOS or soluble guanylate cyclase in vivo and in vitro, we show that the NO‐cGMP pathway induces endogenous galanin in DRG neurons. We propose that both LIF and NO, acting at different promoter regions, are important for the up‐regulation of galanin, and for DRG neuron survival and regeneration after axotomy.
Nitric oxide regulates cell survival in purified cultures of avian retinal neurons: involvement of multiple transduction pathways
Authors: Mejía‐García T. A. , Paes‐de‐Carvalho R. 
Published: November 2006

AbstractNitric oxide (NO) is an important signaling molecule in the CNS, regulating neuronal survival, proliferation and differentiation. Here, we explored the mechanism by which NO, produced from the NO donor S‐nitroso‐acetyl‐d‐l‐penicillamine (SNAP), exerts its neuroprotective effect in purified cultures of chick retinal neurons. Cultures prepared from 8‐day‐old chick embryo retinas and incubated for 24 h (1 day in culture, C1) were treated or not with SNAP, incubated for a further 72 h (up to 4 days in culture, C4), fixed, and the number of cells estimated, or processed for cell death estimation, by measuring the reduction of the metabolic dye 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT). Experimental cultures were run in parallel but were re‐fed with fresh medium in the absence or presence of SNAP at culture day 3 (C3), incubated for a further 24 h up to C4, then fixed or processed for the MTT assay. Previous studies showed that the re‐feeding procedure promotes extensive cell death. SNAP prevented this death in a concentration‐ and time‐dependent manner through the activation of soluble guanylate cyclase; this protection was significantly reversed by the enzyme inhibitors 1H‐[1,2,4]oxadiazolo‐[4,3‐a]quinoxalin‐1‐one (ODQ) or LY83583, and mimicked by 8‐bromo cyclic guanosine 5′‐phosphate (8Br‐cGMP) (GMP) or 3‐(5′‐hydroxymethyl‐2′‐furyl)‐1‐benzyl indazole (YC‐1), guanylate cyclase activators. The effect was blocked by the NO scavenger 2‐phenyl‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl‐3‐oxide (PTIO). The effect of NO was also suppressed by LY294002, Wortmannin, PD98059, KN93 or H89, indicating the involvement, respectively, of phosphatidylinositol‐3 kinase, extracellular‐regulated kinases, calmodulin‐dependent kinases and protein kinase A signaling pathways. NO also induced a significant increase of neurite outgrowth, indicative of neuronal differentiation, and blocked cell death induced by hydrogen peroxide. Cyclosporin A, an inhibitor of the mitochondrial permeability transition pore considered an important mediator of apoptosis and necrosis, as well as boc‐aspartyl (OMe) fluoromethylketone (BAF), a caspase inhibitor, also blocked cell death induced by re‐feeding the cultures. These findings demonstrate that NO inhibits apoptosis of retinal neurons in a cGMP/protein kinase G (PKG)‐dependent way, and strengthens the notion that NO plays an important role during CNS development.
Expression and localization of Parkinson's disease‐associated leucine‐rich repeat kinase 2 in the mouse brain
Authors: Higashi Shinji , Moore Darren J. , Colebrooke Rebecca E. , Biskup Saskia , Dawson Valina L. , Arai Heii , Dawson Ted M. , Emson Piers C. 
Published: November 2006

AbstractMutations in the gene encoding leucine‐rich repeat kinase 2 (LRRK2) have been identified as the cause of familial Parkinson's disease (PD) at the PARK8 locus. To begin to understand the physiological role of LRRK2 and its involvement in PD, we have investigated the distribution of LRRK2 mRNA and protein in the adult mouse brain. In situ hybridization studies indicate sites of mRNA expression throughout the mouse brain, with highest levels of expression detected in forebrain regions, including the cerebral cortex and striatum, intermediate levels observed in the hippocampus and cerebellum, and low levels in the thalamus, hypothalamus and substantia nigra. Immunohistochemical studies demonstrate localization of LRRK2 protein to neurones in the cerebral cortex and striatum, and to a variety of interneuronal subtypes in these regions. Furthermore, expression of LRRK2 mRNA in the striatum of VMAT2‐deficient mice is unaltered relative to wild‐type littermate controls despite extensive dopamine depletion in this mouse model of parkinsonism. Collectively, our results demonstrate that LRRK2 is present in anatomical brain regions of direct relevance to the pathogenesis of PD, including the nigrostriatal dopaminergic pathway, in addition to other regions unrelated to PD pathology, and is likely to play an important role in the normal function of telencephalic forebrain neurones and other neuronal populations.
Dichloroacetate causes reversible demyelination in vitro: potential mechanism for its neuropathic effect
Authors: Felitsyn Natalia , Stacpoole Peter W. , Notterpek Lucia 
Published: November 2006

AbstractDichloroacetate (DCA) is an investigational drug for genetic mitochondrial diseases whose use has been mitigated by reversible peripheral neuropathy. We investigated the mechanism of DCA neurotoxicity using cultured rat Schwann cells (SCs) and dorsal root ganglia (DRG) neurons. Myelinating SC‐DRG neuron co‐cultures, isolated SCs and DRG neurons were exposed to 1–20 mm DCA for up to 12 days. In myelinating co‐cultures, DCA caused a dose‐ and exposure‐dependent decrease of myelination, as determined by immunolabeling and immunoblotting for myelin basic protein (MBP), protein zero (P0), myelin‐associated glycoprotein (MAG) and peripheral myelin protein 22 (PMP22). Partial recovery of myelination occurred following a 10‐day washout of DCA. DCA did not affect the steady‐state levels of intermediate filament proteins, but promoted the formation of anti‐neurofilament antibody reactive whirls. In isolated SC cultures, DCA decreased the expression of P0 and PMP22, while it increased the levels of p75NTR (neurotrophin receptor), as compared with non‐DCA‐treated samples. DCA had modest adverse effects on neuronal and glial cell vitality, as determined by the release of lactate dehydrogenase. These results demonstrate that DCA induces a reversible inhibition of myelin‐related proteins that may account, at least in part, for its clinical peripheral neuropathic effects.
Brain‐derived neurotrophic factor regulates the expression of D1 dopamine receptors
Authors: Do Thuy , Kerr Bredford , Kuzhikandathil Eldo V. 
Published: November 2006

AbstractWe have previously demonstrated that the CAD catecholaminergic neuronal cell line is an appropriate model system to study the regulation of D1 dopamine receptor expression. In this report, we show that brain‐derived neurotrophic factor (BDNF) up‐regulates the expression of D1 dopamine receptor in CAD cells. In addition, by comparing D1 receptor mRNA expression in wild‐type, heterozygous and homozygous trkB knockout mice, we show that TrkB receptor signaling up‐regulates D1 receptor expression in vivo. In CAD cells expressing the TrkB receptor, BDNF increased D1 receptor mRNA in a time‐ and dose‐dependent manner with a fourfold increase in D1 receptor mRNA observed as early as 3 h with 10 ng/mL of BDNF. Using different classes and concentrations of kinase inhibitors, we determined that BDNF‐induced increase of D1 receptor mRNA is mediated by the phosphatidylinositol 3‐kinase signaling pathway. The increase required both new transcription and protein synthesis, as it was blocked by actinomycin D and cyclohexamide, respectively. Promoter deletion analysis identified a D1 promoter region necessary for mediating the effect of BDNF. These results provide novel evidence that D1 dopamine receptor expression is regulated by BDNF and its signaling pathway.
Supercritical Fluids and the Food Industry
Authors: Rozzi N.L. , Singh R.K. 
Published: November 2006

AbstractThis paper reviews the use of supercritical fluids in various aspects of the food industry, and is divided into six different areas: modeling of supercritical fluids, separation of extracted material, supercritical carbon dioxide as a solvent for extraction, supercritical fluids and analytical uses, and supercritical fluids and novel methods of food processing. An assortment of solutes are covered in the extraction section of the paper, including antineoplastic agents and lipids. The analytical methods section covers supercritical fluid chromatography, pesticide detection, and lipid analysis. The novel methods section discusses supercritical fluid extrusion and a new method of eliminating hexane from soybean oil.
Release and Transport of Flavors In Vivo: Physicochemical, Physiological, and Perceptual Considerations
Authors: Taylor A. J. 
Published: November 2006

ABSTRACTFor flavor perception to occur, the chemicals responsible for flavor perception must be released from the food matrix and transported to the flavor receptors in the mouth and nose. The overall process is governed by the properties of the flavor compounds, the nature of the food matrix and the physiological conditions of the mouth, nose and throat during consumption of the food. These factors combine to determine the concentrations and rate at which the flavor chemicals reach the receptors, thus creating the characteristic flavor profile of a food. Physicochemical factors like partitioning, interfacial mass transport and diffusion are the typical mechanisms governing flavor release. Although the theory behind these factors is well understood, applying them to the situation in‐mouth during eating is difficult. This is because key parameters like surface area and flavor concentrations in the gas and liquid phases change rapidly with time as a result of the physiological processes occurring during eating. Furthermore, individuals vary in their rate of breathing, swallowing and salivation, which affects the transport of flavors from the saliva phase to receptors on the tongue and in the nose. This review covers all aspects of flavor release from food matrices and the subsequent delivery of flavor to the olfactory and gustatory receptors.
Chemistry and Reaction of Singlet Oxygen in Foods
Authors: Min D. B. , Boff J. M. 
Published: November 2006

ABSTRACTSinglet oxygen is a highly reactive, electrophilic, and nonradical molecule. It is different from diradical triplet oxygen in its electron arrangement. Photosensitizers can form singlet oxygen from triplet oxygen in the presence of light. The reaction rate of singlet oxygen with foods is much greater than that of triplet oxygen due to the low activation energy. Singlet oxygen oxidation produces undesirable compounds in foods during processing and storage. However, carotenoids and tocopherols in foods can minimize singlet oxygen oxidation. The in‐depth scientific knowledge on the formation, reactions, quenching mechanisms, and kinetics of singlet oxygen can greatly improve the quality of foods by minimizing the oxidation during processing and storage. The single oxygen oxidation of foods has contributed to the explanation of several important chemical reactions in the reversion flavor in soybean oil, sunlight flavor in milk products, and the rapid losses of vitamin D, riboflavin, and ascorbic acid in milk under light storage.