bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic analysis of protein changes developing in rat hippocampus after chronic antidepressant treatment: Implications for depressive disorders and future therapies
Authors: Khawaja Xavier , Xu Jun , Liang Jin‐Jun , Barrett James E. 
Published: January 2004

AbstractIt is recognized that monoamine reuptake inhibitors (MARIs) exert beneficial effects in the treatment of major depression and general anxiety disorder. The aim of this study was to identify proteins regulated by this class of antidepressant using a proteome differential profiling approach. Either venlafaxine or fluoxetine was administered systemically to adult rats for 2 weeks, and protein patterns from rat hippocampal cytosolic extracts were compared by two‐dimensional gel electrophoresis. Silver‐stained protein spots displaying differential expression were identified by mass spectrometry. Thirty‐three protein spots were modulated by both drug treatments compared to controls. The classification of several proteins that were sorted by function suggested convergent pathway activities for both MARIs at the post‐receptor level. These included proteins associated with neurogenesis (insulin like growth factor 1 (IGF‐1), glia maturation factor [GMF]‐β), outgrowth/maintenance of neuronal processes (hippocampal cholinergic neurostimulating peptide [HCNP], PCTAIRE‐3), and with neural regeneration/axonal guidance collapsin response mediator protein (CRMP‐2) systems. Other modulated proteins indicated an increase in neuronal vesicular cell trafficking and synaptic plasticity (Ras‐related protein 4a (Rab4a), Ras‐related protein 1b (Rab1b), heat shock protein 10 [HSP10]), as well as neurosteroidogenic (hydroxysteroid sulfotransferase A) and possible anti‐apoptotic (dimethylargininase‐1 L‐N,N‐dimethylarginine dimethylaminohydrolase‐1 [DDAH‐1], pyruvate dehydrogenase‐E1 [PDH‐E1], antioxidant protein‐2 [AOP‐2]) pathway‐mediated regulatory events. Parallel studies to investigate further the effects of venlafaxine and fluoxetine on adult hippocampal neurogenesis in vivo by quantitative bromodeoxyuridine immunolabeling revealed a significant drug‐induced increase in the proliferation rate and long‐term survivability of progenitor stem cells located in the subgranular zone. These data suggest that MARIs share wide‐ranging proteome changes within the hippocampal formation, beyond 5‐HT/NE neurotransmission. This may reflect long‐term functional adaptations required for antidepressant activity. © 2004 Wiley‐Liss, Inc.
Suppression of proliferation and neurite extension of human neuroblastoma SH‐SY5Y cells on immobilized Psathyrella velutina lectin
Authors: Kitamura Noriaki , Ikekita Masahiko , Hayakawa Satoru , Funahashi Hisayuki , Furukawa Kiyoshi 
Published: January 2004

AbstractGlycoproteins from mammalian brain tissues contain unique N‐linked oligosaccharides terminating with β‐N‐acetylglucosamine residues. Lectin blot analysis of membrane glycoprotein samples from human neuroblastoma SH‐SY5Y cells showed that several protein bands bind to Psathylera velutina lectin (PVL), which interacts with β‐N‐acetylglucosamine‐terminating oligosaccharides. No lectin positive bands were detected by digestion with jack bean β‐N‐acetyl‐hexosaminidase or N‐glycanase before incubation with the lectin, indicating that the cells contain β‐N‐acetylglucosamine‐terminating N‐linked oligosaccharides. When cells were cultured in dishes with different concentrations of PVL, the cell proliferation was inhibited in a dose‐dependent manner. Similarly, the neurite extension, which was stimulated with nerve growth factor, was also inhibited in a manner dependent on the lectin dose. Cell proliferation and neurite extension were recovered by the addition of 10 mM N‐acetylglucosamine into the medium. Immunoblot analysis of the activation of mitogen‐activated protein (MAP) kinases and protein kinase C revealed that phosphorylation of 42‐kDa and 44‐kDa MAP kinases and 80‐kDa protein kinase C are inhibited when SH‐SY5Y cells are cultured in PVL‐coated dishes, but are restored by the addition of the haptenic sugar into the medium, indicating that MAP kinase and protein kinase C pathways are inhibited by interaction with immobilized PVL. These results indicate that β‐N‐acetylglucosamine‐terminating N‐linked oligosaccharides expressed on neural cells can induce intracellular signals upon binding to extracellular receptors, and are important for growth regulation of neural cells. © 2003 Wiley‐Liss, Inc.
Sulfate‐ and size‐dependent polysaccharide modulation of AMPA receptor properties
Authors: Chicoine Linda M. , Suppiramaniam Vishnu , Vaithianathan Thirumalini , Gianutsos Gerald , Bahr Ben A. 
Published: January 2004

AbstractPrevious work found evidence that α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA)‐type glutamate receptors interact with and are functionally regulated by the glycosaminoglycan heparin. The present study tested whether dextran species affect ligand binding, channel kinetics, and calcium permeability of AMPA receptors. Dextran sulfate of 500 kDa markedly reduced high affinity [3H]AMPA binding in solubilized hippocampal membranes. In isolated receptors reconstituted in a lipid bilayer, the same dextran sulfate prolonged the lifetime of open states exhibited by AMPA‐induced channel fluctuations. The large polysaccharide further changed the single channel kinetics by increasing the open channel probability five‐ to sixfold. Such modulation of channel activity corresponded with enhanced levels of calcium influx as shown in hippocampal neurons loaded with Fluo3AM dye. With an exposure time of <1 min, AMPA produced a dose‐dependent increase in intracellular calcium that was blocked by 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione disodium (CNQX). Dextran sulfate, at the same concentration range that modified ligand binding (EC50 of 5–10 nM), enhanced the AMPA‐induced calcium influx by as much as 60%. The enhanced influx was blocked by CNQX, although unchanged by the N‐methyl‐D‐aspartate (NMDA) receptor antagonist AP5. Confocal microscopy showed that the increase in calcium occurred in neuronal cell bodies and their processes. Interestingly, smaller 5–8‐kDa dextran sulfate and a non‐sulfated dextran of 500 kDa had little or no effect on the binding, channel, and calcium permeability properties. Together, these findings suggest that synaptic polysaccharide species modulate hippocampal AMPA receptors in a sulfate‐ and size‐dependent manner. © 2003 Wiley‐Liss, Inc.
A non‐peptide substance P antagonist (CP‐96,345) inhibits morphine‐induced NF‐κB promoter activation in human NT2‐N neurons
Authors: Wang Xu , Douglas Steven D. , Commons Kathryn G. , Pleasure David E. , Lai Jianping , Ho Chun , Bannerman Peter , Williams Marge , Ho Wenzhe 
Published: January 2004

AbstractOpioids and the neuropeptide substance P (SP) modulate the expression of inflammatory cytokines and chemokines, which are under the control of nuclear factor κB (NF‐κB). We investigated whether the neurokinin‐1 receptor (SP receptor) pathway is biologically involved in morphine‐mediated modulation of NF‐κB promoter activation in a human neuronal cell line (NT2‐N) that expresses both the mu‐opioid receptor (MOR) and the SP receptor. Morphine significantly enhanced NF‐κB promoter‐directed luciferase activity in NT2‐N neurons. DAMGO, a selective mu‐opioid receptor agonist, also induced NF‐κB promoter activation. The induced activation of NF‐κB promoter by morphine or DAMGO was abolished not only by naltrexone (a opioid receptor antagonist) and CTAP (a selective, competitive mu‐opioid receptor antagonist), but also by CP‐96,345, a non‐peptide SP receptor antagonist. Investigation of the mechanism responsible for morphine‐induced activation of NF‐κB promoter in NT2‐N neurons demonstrated that morphine activates the SP promoter and induces SP expression in these cells. We also observed that SP activated NF‐κB promoter and that CP‐96,345 downregulated the expression of endogenous SP. Furthermore, dual immunofluorescent labeling revealed that there is co‐expression of NK‐1R and MOR in the processes of NT‐2N neurons. These results suggest that morphine, by activating MOR, engages a positive feedback loop between NK‐1R and SP. Activation of NK‐1R could then impact NF‐κB expression and therefore may be an important participant in the effect of morphine on immune responses in the central nervous system. © 2003 Wiley‐Liss, Inc.
Regulation of a Ca2+‐activated K+ channel by calcium‐sensing receptor involves p38 MAP kinase
Authors: Ye Chian Ping , Yano Shozo , Tfelt‐Hansen Jacob , MacLeod R. John , Ren Xianghui , Terwilliger Ernest , Brown Edward M. , Chattopadhyay Naibedya 
Published: January 2004

AbstractBy using pharmacological and molecular approaches, we previously showed that the G‐protein‐coupled, extracellular calcium (Ca)‐sensing receptor (CaR) regulates a large‐conductance (∼140 pS), Ca2+‐activated K+ channel [IK(Ca); CAKC] in U87 astrocytoma cells. Here we show that elevated Ca stimulates extracellular‐signal‐regulated kinase (ERK1/2) and p38 MAP kinase (MAPK). The effect of high Ca on p38 MAPK but not ERK1/2 is CaR mediated, insofar as transduction with a dominant‐negative CaR (R185Q) using recombinant adeno‐associated virus (rAAV) attenuated the activation of p38 MAPK but not of ERK1/2. p38 MAPK activation by the CaR is likely to be protein kinase C (PKC) independent, in that the pan‐PKC inhibitor GF109203X failed to abolish the high‐Ca‐induced phosphorylation of p38 MAPK. Consistently with our data on the activation of this kinase, we observed that inhibiting p38 MAPK blocked the activation of the CAKC induced by the specific pharmacological CaR activator NPS R‐467. In contrast, inhibiting MEK1 only transiently inhibited the activation of this K+ channel by NPS R‐467, despite the continued presence of the antagonist. Similarly to the lack of any effect of the PKC inhibitor on the activation of ERK1/2 and p38 MAPK, inhibiting PKC had no effect on NPS R‐467‐induced activation of this channel. Therefore, our data show that the CaR, acting via p38 MAPK, regulates a large‐conductance CAKC in U87 cells, a process that is PKC independent. Large‐conductance CAKCs play an important role in the regulation of cellular volume, so our results have important implications for glioma cell volume regulation. © 2004 Wiley‐Liss, Inc.
Anti‐Aβ: The good, the bad, and the unforeseen
Authors: Broytman Oleg , Malter James S. 
Published: January 2004

AbstractAlzheimer's disease (AD) is characterized in part by the deposition of amyloid β protein (Aβ) in compact fibrillar plaques. These structures can induce an innate immune response in the brain, which triggers progressive inflammation, neuronal loss, and further acceleration of Aβ plaque formation. Compared with the case in normal individuals, the T and B lymphocytes in AD patients and murine models are hyporesponsive to Aβ. However, depending on the route of delivery, tolerance can be overcome by vaccination, with the induction of an anti‐Aβ‐mediated immune response. Through mechanisms that are incompletely understood, immunized APP transgenic animals show markedly reduced Aβ deposition, preservation of normal neuronal architecture, and improved performance in memory and spatial learning tasks. In human trials, Aβ vaccination stabilized cognition and slowed the progression of dementia. Neuropathologic examination of a vaccinated subject showed reduced cortical Aβ without changes in other AD‐associated pathology. However, in some patients, vaccination induced severe meningoencephalitis, causing the trial to be terminated. Thus, vaccination appears to activate both beneficial and deleterious anti‐Aβ immunity, suggesting that the vaccine can have potent clinical utility if an appropriate immunologic response can be generated. © 2003 Wiley‐Liss, Inc.
TNFα increases activity of γ‐glutamyl transpeptidase in cultured rat astroglial cells
Authors: Ruedig Cornelia , Dringen Ralf 
Published: January 2004

AbstractTo investigate the presence of γ‐glutamyl transpeptidase (γGT) in brain cells, cultures enriched for astroglial cells, neurons, oligodendroglial cells, and microglial cells were studied. Astroglial cultures contained a specific γGT activity of 2.3 ± 0.9 nmol/min/mg protein. A similar specific γGT activity was measured for oligodendroglial cultures, whereas microglial cells and neurons contained less than 30% of the specific γGT activity of astroglial cultures. The activity of γGT in astroglial cultures was elevated strongly by the presence of tumor necrosis factor‐α (TNFα) in a time‐ and concentration‐dependent manner. Maximal activity of γGT was observed after incubation of astroglial cultures for 3 days with 30 ng/mL TNFα. Under these conditions the specific γGT activity was increased by threefold compared to controls. Presence of the γGT‐inhibitor acivicin completely inhibited γGT activity both in TNFα‐treated and in control cells. In addition, the increase in astroglial γGT activity after application of TNFα was prevented completely by the presence of the protein synthesis inhibitor cycloheximide. γGT is involved in extracellular processing of glutathione (GSH) that is exported by astroglial cells. After TNFα‐treatment the concentration of GSH in the medium of astroglial cells was reduced significantly compared to control cells. In conclusion, the data presented demonstrate that TNFα stimulates γGT synthesis in astroglial cells and thereby improves the capacity to process GSH exported by these cells. © 2003 Wiley‐Liss, Inc.
Identification of a protein that interacts with the golli‐myelin basic protein and with nuclear LIM interactor in the nervous system
Authors: Fernandes Augustine O. , Campagnoni Celia W. , Kampf Kathy , Feng Ji‐Ming , Handley Vance W. , Schonmann Vilma , Bongarzone Ernesto R. , Reyes Sam , Campagnoni Anthony T. 
Published: January 2004

AbstractThe myelin basic protein (MBP) gene encodes the classic MBPs and the golli proteins, which are related structurally to the MBPs but are not components of the myelin sheath. A yeast two‐hybrid approach was used to identify molecular partners that interact with the golli proteins. A mouse cDNA was cloned that encoded a protein of 261 amino acids and called golli‐interacting protein (GIP). Database analysis revealed that GIP was the murine homolog of human nuclear LIM interactor‐interacting factor (NLI‐IF), a nuclear protein whose function is just beginning to be understood. It is a member of a broad family of molecules, found in species ranging from yeast to human, that contain a common domain of ∼100 amino acids. Immunocytochemical and Northern blot analyses showed co‐expression of GIP and golli in several neural cell lines. GIP and golli also showed a similar developmental pattern of mRNA expression in brain, and immunohistochemical staining of GIP and golli showed co‐expression in several neuronal populations and in oligodendrocytes in the mouse brain. GIP was localized predominantly in nuclei. GIP co‐immunoprecipitated with golli in several in vitro assays as well as from PC12 cells under physiologic conditions. GIP was the first member of this family shown to interact with nuclear LIM interactor (NLI). NLI co‐immunoprecipitated with GIP and golli from lysates of N19 cells transfected with NLI, further confirming an interaction between golli, GIP, and NLI. The ability of GIP to interact with both golli and NLI, and the nuclear co‐localization of GIP and golli in many cells, indicates a role for the golli products of the MBP gene in NLI‐ associated regulation of gene expression. © 2003 Wiley‐Liss, Inc.
CD4 T‐cell epitopes of human α B‐crystallin
Authors: Chou Yuan K. , Burrows Gregory G. , LaTocha Dorian , Wang Chunhe , Subramanian Sandhya , Bourdette Dennis N. , Vandenbark Arthur A. 
Published: January 2004

AbstractOf potential importance to multiple sclerosis (MS), oligodendroglial α B‐crystallin is expressed and associated with the myelin sheath at the earliest stage of MS lesion development. We selected T‐cell lines specific for human α B‐crystallin from peripheral blood mononuclear cells (PBMC) of HLA‐DR2 homozygous MS patients and found that the α B‐crystallin‐specific T‐cells were CD4+ and restricted by DRB1*1501, and expressed Th1 cytokines. The CD4 T‐cell epitopes of human α B‐crystallin were determined by proliferation of α B‐crystallin‐specific T‐cell lines to 17 20‐mer synthetic overlapping peptides spanning the entire molecule of human α B‐crystallin. It was found that the HLA‐DR2 donor‐derived α B‐crystallin‐specific T‐cell lines proliferated to α B‐crystallin peptides 21–40, 41–60, and to a lesser extent, 131–150. These T‐cell proliferation responses were associated with intracellular expression of interleukin‐2 (IL‐2) and secretion of interferon‐γ (IFN‐γ), and tumor necrosis factor‐α (TNF‐α). The amino acid sequences of these peptides were compatible with predicted HLA‐DR2‐restricted binding motifs. PBMC of an early active MS patient proliferated to the epitope‐containing peptides significantly better than did those of later stage MS patients or healthy controls. Taken together, these findings suggest that autoreactive α B‐crystallin‐specific Th1 cells may have the potential to contribute to MS pathogenesis. © 2004 Wiley‐Liss, Inc.
Enhanced inflammatory response in neural tubes of embryos derived from diabetic mice exposed to a teratogen
Authors: Lian Qizhou , Dheen S. Thameem , Liao Dongmei , Tay Samuel Sam Wah 
Published: January 2004

AbstractExposure of embryos to the teratogen cyclophosphamide (CP) and maternal diabetes is linked to pathogenesis of neural tube defects during development. Maternal diabetes aggravates the teratogen‐induced inflammatory reaction leading to increased risk of neural tube defects in mouse embryos. The inflammatory reaction in the developing neural tube has been characterized by the presence of activated amoeboid microglia/brain macrophages and altered expression levels of cytokines. Although there were no obvious anomalies observed in the neural tubes of embryos from CP‐treated non‐diabetic mice, the frequency of neural tube defects was increased significantly in embryos of CP‐treated diabetic mice. Moreover, there were more activated amoeboid microglia in the forebrain of CP‐treated diabetic embryos compared to that in CP‐treated non‐diabetic mice. The expression of cytokines such as tumor necrosis factor‐α (TNF‐α) and transforming growth factor‐β1 (TGF‐β1) in the fetal brain of normal and diabetic embryos was induced in the neural tubes after CP treatment. Furthermore, the mRNA expression levels of both genes were increased markedly in the neural tube of CP‐treated diabetic embryos compared to that of CP‐treated non‐diabetic embryos as measured by quantitative real‐time PCR. Immunohistochemically, more TNF‐α‐ and TGF‐β1‐positive cells, which included neurons and amoeboid microglia, were detected in CP‐treated diabetic embryos than in CP‐treated normal embryos. Maternal diabetes aggravates teratogen‐induced inflammation, which is characterized in the developing neural tube by increased amoeboid microglia and enhanced expression of inflammatory cytokines. Although a definite link has yet to be elucidated, it is suggested that the increased rate of neural tube defects observed in CP‐treated diabetic embryos may be due to upregulation of proinflammatory cytokines caused by maternal diabetes. © 2004 Wiley‐Liss, Inc.
Differential subcellular distribution of Ca2+/calmodulin‐dependent protein kinase II isoforms in the striatum and NG108‐15 cells
Authors: Takeuchi Yusuke , Nomura Kazumi , Fukunaga Kohji 
Published: January 2004

AbstractFour subunits of Ca2+/calmodulin‐dependent protein kinase II (CaM KII) have several isoforms, which differ in the variable domain. We previously reported that all subunits were highly expressed in rat striatal neurons. To examine intracellular distributions of CaM KII subunits in the rat striatal neurons, we performed immunoblot analysis with antibodies specific to each subunit in cell extracts from the rat striatum after continuous sucrose density gradient fractionation. The α subunit, but not the β, γ, or δ subunits, was colocalized with synapsin I, and each subunit showed a distinct distribution pattern in the fractions. To examine further the intracellular distributions of CaM KII isoforms in the same subunit, we established NG108‐15 cells stably expressing δ1, δ3, and δ4 isoforms and examined distributions of the δ and γ isoforms in these cell lines after fractionation. Each of the overexpressed exogenous δ isoforms showed a distinct distribution pattern. The endogenous δ2 was colocalized with the overexpressed δ1, δ3, and δ4 isoforms. However, the endogenous γB/γC isoforms were not colocalized with the overexpressed δ isoforms. Furthermore, the endogenous δ1 was concentrated in the microsomal fraction from the rat striatum. With the results taken together, it is suggested that CaM KII forms oligomers between isoforms in the same subunit but not in different subunits. The variable domain of CaM KII isoforms might possibly be responsible for targeting to certain intracellular compartments. © 2004 Wiley‐Liss, Inc.
Noise trauma alters D‐[3H]aspartate release and AMPA binding in chinchilla cochlear nucleus
Authors: Muly S.M. , Gross J.S. , Potashner S.J. 
Published: January 2004

AbstractExposure of adults to loud noise can overstimulate the auditory system, damage the cochlea, and destroy cochlear nerve axons and their synaptic endings in the brain. Cochlear nerve loss probably results from the death of cochlear inner hair cells (IHC). Additional degeneration in the cochlear nucleus (CN) is hypothesized to stem from overstimulation of the system, which may produce excitotoxicity. This study tested these predictions by exposing one ear of anesthetized adult chinchillas to a loud noise, which damaged the ipsilateral cochlea and induced degeneration in the glutamatergic cochlear nerve. During the first postexposure week, before cochlear nerve axons degenerated, glutamatergic synaptic release in the ipsilateral CN was elevated and uptake was depressed, consistent with hyperactivity of glutamatergic transmission and perhaps with the operation of an excitotoxic mechanism. By 14 days, when cochlear nerve fibers degenerated, glutamatergic synaptic release and uptake in the CN became deficient. By 90 days, a resurgence of transmitter release and an elevation of AMPA receptor binding suggested transmission upregulation through plasticity that resembled changes after mechanical cochlear damage. These changes may contribute to tinnitus and other pathologic symptoms that precede and accompany hearing loss. In contrast, the other ear, protected with a silicone plug during the noise exposure, exhibited virtually no damage in the cochlea or the cochlear nerve. Altered glutamatergic release and AMPA receptor binding activity in the CN suggested upregulatory plasticity driven by signals emanating from the CN on the noise‐exposed side. © 2004 Wiley‐Liss, Inc.