bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased TCA cycle rate in the rat brain after acute 3‐NP treatment measured by in vivo1H‐{13C} NMR spectroscopy
Authors: Henry Pierre‐Gilles , Lebon Vincent , Vaufrey Françoise , Brouillet Emmanuel , Hantraye Philippe , Bloch Gilles 
Published: March 2003

AbstractInhibition of succinate dehydrogenase (SDH) by the mitochondrial toxin 3‐nitropropionic acid (3‐NP) has gained acceptance as an animal model of Huntington's disease. In this study 13C NMR spectroscopy was used to measure the tricarboxylic acid (TCA) cycle rate in the rat brain after 3‐NP treatment. The time course of both glutamate C4 and C3 13C labelling was monitored in vivo during an infusion of [1‐13C]glucose. Data were fitted by a mathematical model to yield the TCA cycle rate (Vtca) and the exchange rate between α‐ketoglutarate and glutamate (Vx). 3‐NP treatment induced a 18% decrease in Vtca from 0.71 ± 0.02 µmol/g/min in the control group to 0.58 ± 0.02 µmol/g/min in the 3‐NP group (p < 0.001). Vx increased from 0.88 ± 0.08 µmol/g/min in the control group to 1.33 ± 0.24 µmol/g/min in the 3‐NP group (p < 0.07). Fitting the C4 glutamate time course alone under the assumption that Vx is much higher than Vtca yielded Vtca=0.43 µmol/g/min in both groups. These results suggest that both Vtca and Vx are altered during 3‐NP treatment, and that both glutamate C4 and C3 labelling time courses are necessary to obtain a reliable measurement of Vtca.
Region‐selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain
Authors: Biegon A. , Alvarado M. , Budinger T. F. , Grossman R. , Hensley K. , West M. S. , Kotake Y. , Ono M. , Floyd R. A. 
Published: March 2003

AbstractFollowing induction of acute neuroinflammation by intracisternal injection of endotoxin (lipopolysaccharide) in rats, quantitative autoradiography was used to assess the regional level of microglial activation and glutamate (NMDA) receptor binding. The possible protective action of the antioxidant phenyl‐tert‐butyl nitrone in this model was tested by administering the drug in the drinking water for 6 days starting 24 hafter endotoxin injection. Animals were killed 7 days post‐injection and consecutive cryostat brain sections labeled with [3H]PK11195 as a marker of activated microglia and [125I]iodoMK801 as a marker of the open‐channel, activated state of NMDA receptors. Lipopolysaccharide increased [3H]PK11195 binding in the brain, with the largest increases (two‐ to threefold) in temporal and entorhinal cortex, hippocampus, and substantia innominata. A significant (> 50%) decrease in [125I]iodoMK801 binding was found in the same brain regions. Phenyl‐tert‐butyl nitrone treatment resulted in a partial inhibition (approx. 25% decrease) of the lipopolysaccharide‐induced increase in [3H]PK11195 binding but completely reversed the lipopolysaccharide‐induced decrease in [125I]iodoMK80 binding in the entorhinal cortex, hippocampus, and substantia innominata. Loss of NMDA receptor function in cortical and hippocampal regions may contribute to the cognitive deficits observed in diseases with a neuroinflammatory component, such as meningitis or Alzheimer's disease.
Endoplasmic reticulum calcium release is modulated by actin polymerization
Authors: Wang Yue , Mattson Mark P. , Furukawa Katsutoshi 
Published: March 2003

AbstractIntracellular calcium ions regulate the structure and functions of cytoskeletal proteins. On the other hand, recent studies have shown that the cytoskeleton, and actin filaments in particular, can modulate calcium influx through plasma membrane ligand‐ and voltage‐gated channels. We now report that calcium release from inositol trisphosphate (IP3) and ryanodine‐sensitive endoplasmic reticulum (ER) stores is modulated by polymerization and depolymerization of actin filaments in cultured hippocampal neurons. Depolymerization of actin filaments with cytochalasin D attenuates calcium release induced by carbamylcholine (CCh; a muscarinic agonist for IP3 pathway), caffeine (a ryanodine receptor agonist) and thapsigargin (an inhibitor of the ER calcium‐ ATPase) in both the presence and absence of extracellular calcium. Conversely, the actin polymerizing agent jasplakinolide potentiates calcium release induced by CCh, caffeine and thapsigargin. Cytochalasin D attenuated, while jasplakinolide augmented, thapsigargin‐induced JNK activation and neuronal cell death. Our data show that the actin cytoskeleton regulates ER calcium release, suggesting roles for actin in the various physiological and pathological processes that involve calcium release.
Regional and cellular expression of CYP2D6 in human brain: higher levels in alcoholics
Authors: Miksys Sharon , Rao Yushu , Hoffmann Ewa , Mash Deborah C. , Tyndale Rachel F. 
Published: March 2003

AbstractCytochrome P450 (CYP) 2D6 is expressed in liver, brain and other extrahepatic tissues where it metabolizes a range of centrally acting drugs and toxins. As ethanol can induce CYP2D in rat brain, we hypothesized that CYP2D6 expression is higher in brains of human alcoholics. We examined regional and cellular expression of CYP2D6 mRNA and protein by RT‐PCR, Southern blotting, slot blotting, immunoblotting and immunocytochemistry. A significant correlation was found between mean mRNA and CYP2D6 protein levels across 13 brain regions. Higher expression was detected in 13 brain regions of alcoholics (n = 8) compared to nonalcoholics (n = 5) (anovap < 0.0001). In hippocampus this was localized in CA1–3 pyramidal cells and dentate gyrus granular neurons. In cerebellum this was localized in Purkinje cells and their dendrites. Both of these brain regions, and these same cell‐types, are known to be susceptible to alcohol damage. For one case, a poor metabolizer (CYP2D6*4/*4), there was no detectable CYP2D6 protein, confirming the specificity of the antibody used. These data suggest that in alcoholics elevated brain CYP2D6 expression may contribute to altered sensitivity to centrally acting drugs and to the mediation of neurotoxic and behavioral effects of alcohol.
Evidence that brain‐derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice
Authors: Lee Jaewon , Duan Wenzhen , Mattson Mark P. 
Published: March 2003

AbstractTo determine the role of brain‐derived neurotrophic factor (BDNF) in the enhancement of hippocampal neurogenesis resulting from dietary restriction (DR), heterozygous BDNF knockout (BDNF +/–) mice and wild‐type mice were maintained for 3 months on DR or ad libitum (AL) diets. Mice were then injected with bromodeoxyuridine (BrdU) and killed either 1 day or 4 weeks later. Levels of BDNF protein in neurons throughout the hippocampus were decreased in BDNF +/– mice, but were increased by DR in wild‐type mice and to a lesser amount in BDNF +/– mice. One day after BrdU injection the number of BrdU‐labeled cells in the dentate gyrus of the hippocampus was significantly decreased in BDNF +/– mice maintained on the AL diet, suggesting that BDNF signaling is important for proliferation of neural stem cells. DR had no effect on the proliferation of neural stem cells in wild‐type or BDNF +/– mice. Four weeks after BrdU injection, numbers of surviving labeled cells were decreased in BDNF +/– mice maintained on either AL or DR diets. DR significantly improved survival of newly generated cells in wild‐type mice, and also improved their survival in BDNF +/– mice, albeit to a lesser extent. The majority of BrdU‐labeled cells in the dentate gyrus exhibited a neuronal phenotype at the 4‐week time point. The reduced neurogenesis in BDNF +/– mice was associated with a significant reduction in the volume of the dentate gyrus. These findings suggest that BDNF plays an important role in the regulation of the basal level of neurogenesis in dentate gyrus of adult mice, and that by promoting the survival of newly generated neurons BDNF contributes to the enhancement of neurogenesis induced by DR.
Expression of gp130 and leukaemia inhibitory factor receptor subunits in adult rat sensory neurones: regulation by nerve injury
Authors: Gardiner Natalie J. , Cafferty William B. J. , Slack Sarah E. , Thompson Stephen W. N. 
Published: March 2003

AbstractMembers of the interleukin‐6 (IL‐6) family of cytokines have been implicated as major mediators of the response of the adult nervous system to injury. The basis for an interaction of IL‐6 cytokines with adult sensory neurones has been established by analysing the levels and distribution of the two signal‐transducing receptor subunits, glycoprotein 130 (gp130) and leukaemia inhibitory factor receptor (LIFR), in the dorsal root ganglion (DRG) of male adult rats before and following nerve injury. All sensory neurones express gp130‐immunoreactivity (IR) in the cytoplasm and on the plasma membrane. Levels of gp130 and its intracellular distribution remained unchanged up to 14 days following sciatic nerve axotomy. LIFR‐IR was largely absent from the cytoplasm and plasma membrane of sensory neurones, but confined almost exclusively to the nuclear compartment. However, following axotomy, punctate cytoplasmic LIFR‐IR was detected which persisted up to 28 days following axotomy. The expression of cytoplasmic LIFR 2 days post‐axotomy was proportionally greater in a subset of small diameter sensory neurones which expressed either the sensory neuropeptide CGRP or the cell surface marker isolectin B4. The coexpression of gp130 and LIFR in the same intracellular compartment following axotomy conveys potential responsiveness of injured sensory neurones to members of the IL‐6 family of cytokines.
cDNA array reveals differential gene expression following chronic neuroleptic administration: implications of synapsin II in haloperidol treatment
Authors: Chong Victor Z. , Young L. Trevor , Mishra Ram K. 
Published: March 2003

AbstractThe cDNA expression array is a recently developed scientific tool that can profile the differential expression of several hundreds of genes simultaneously and is therefore advantageous in the study of antipsychotic drug action at the genetic level. Using this technology, we discovered 14 genes in the rat striatum whose expression was changed by ≥ 50% following chronic haloperidol treatment. Among them was the synapsin II gene, which was found to be significantly up‐regulated after the treatment. Since recent studies have implicated this gene in schizophrenia, further experiments were performed to determine whether chronic haloperidol exposure resulted in concurrent increases in the expression of striatal synapsin II protein. Immunoblotting revealed that protein levels of both the a and b isoforms of synapsin II were also increased by comparable amounts following haloperidol treatment. This study is the first to show the regulation of synapsin II expression by haloperidol at the transcript and protein level in rat striatum. A possible mechanism for the observed haloperidol‐induced increase in striatal synapsin II expression, along with the implications of this up‐regulation in chronic haloperidol treatment, is presented.
Mitochondrial electron transport chain complex dysfunction in a transgenic mouse model for amyotrophic lateral sclerosis
Authors: Jung Cheolwha , Higgins Cynthia M. J. , Xu Zuoshang 
Published: March 2003

AbstractAmyotrophic lateral sclerosis is a fatal neurodegenerative disease that causes degeneration of motoneurons. Mutation of Cu,Zn superoxide dismutase (SOD1) is one cause for this disease. In mice, expression of mutant protein causes motoneuron degeneration and paralysis resembling the human disease. Morphological change, indicative of mitochondrial damage, occurs at early stages of the disease. To determine whether mitochondrial function changes during the course of disease progression, enzyme activities of mitochondrial electron transport chain in spinal cords from mice at different disease stages were measured using three different methods: spectrophotometric assay, in situ histochemical enzyme assay, and blue native gel electrophoresis combined with in‐gel histochemical reaction. The enzyme activities were decreased in the spinal cord, particularly in the ventral horn, beginning at early disease stages. This decrease persisted throughout the course of disease progression. This decrease was not detected in the spinal cords of non‐transgenic animals, of mice expressing the wild‐type protein, and in cerebellum and dorsal horn of the spinal cords from mice expressing mutant protein. These results demonstrate a functional defect in mitochondria in the ventral horn region and support the view that mitochondrial damage plays a role in mutant SOD1‐induced motoneuron degeneration pathway.
Internalization of basic fibroblast growth factor at the mouse blood–brain barrier involves perlecan, a heparan sulfate proteoglycan
Authors: Deguchi Yoshiharu , Okutsu Hiroshi , Okura Takashi , Yamada Shizuo , Kimura Ryohei , Yuge Takuro , Furukawa Akihiko , Morimoto Kazuhiro , Tachikawa Masanori , Ohtsuki Sumio , Hosoya Ken‐ichi , Terasaki Tetsuya 
Published: March 2003

AbstractIn this study, the internalization mechanism of basic fibroblast growth factor (bFGF) at the blood–brain barrier (BBB) was investigated using a conditionally immortalized mouse brain capillary endothelial cell line (TM‐BBB4 cells) as an in vitro model of the BBB and the corresponding receptor was identified using immunohistochemical analysis. The heparin‐resistant binding of [125I]bFGF to TM‐BBB4 cells was found to be time‐, temperature‐, osmolarity‐ and concentration‐dependent. Kinetic analysis of the cell‐surface binding of [125I]bFGF to TM‐BBB4 cells revealed saturable binding with a half‐saturation constant of 76 ± 24 nm and a maximal binding capacity of 183 ± 17 pmol/mg protein. The heparin‐resistant binding of [125I]bFGF to TM‐BBB4 was significantly inhibited by a cationic polypeptide poly‐L‐lysine (300 µm), and compounds which contain a sulfate moiety, e.g. heparin and chondroitin sulfate‐B (each 10 µg/mL). Moreover, the heparin‐resistant binding of [125I]bFGF in TM‐BBB4 cells was significantly reduced by 50% following treatment with sodium chlorate, suggesting the loss of perlecan (a core protein of heparan sulfate proteoglycan, HSPG) from the extracellular matrix of the cells. This type of binding is consistent with the involvement HSPG‐mediated endocytosis. RT‐PCR analysis revealed that HSPG mRNA and FGFR1 and FGFR2 (tyrosine‐kinase receptors for bFGF) mRNA are expressed in TM‐BBB4 cells. Moreover, immunohistochemical analysis demonstrated that perlecan is expressed on the abluminal membrane of the mouse brain capillary. These results suggest that bFGF is internalized via HSPG, which is expressed on the abluminal membrane of the BBB. HSPG at the BBB may play a role in maintaining the BBB function due to acceptance of the bFGF secreted from astrocytes.
Abnormal Tau phosphorylation of the Alzheimer‐type also occurs during mitosis
Authors: Delobel Patrice , Flament Stéphane , Hamdane Malika , Mailliot Christel , Sambo Anne‐Véronique , Bégard Séverine , Sergeant Nicolas , Delacourte André , Vilain Jean‐Pierre , Buée Luc 
Published: March 2003

AbstractIn Alzheimer's disease, neurofibrillary degeneration results from the aggregation of abnormally phosphorylated Tau proteins into filaments and it may be related to the reactivation of mitotic mechanisms. In order to investigate the link between Tau phosphorylation and mitosis, Xenopus laevis oocytes in which most of the M‐phase regulators have been discovered were used as a cell model. The human Tau isoform htau412 (2+3–10+) was microinjected into prophase I oocytes that were then stimulated by progesterone that activate cyclin‐dependent kinase pathways. Hyperphosphorylation of the Tau isoform, which is characterized by a decrease of its electrophoretic mobility and its labelling by a number of phosphorylation‐dependent antibodies, was observed at the time of germinal vesicle breakdown. Surprisingly, Tau immunoreactivity, considered as typical of Alzheimer's pathology (AT100 and phospho‐Ser422), was observed in meiosis II. Because meiosis II is considered as a mitosis‐like phase, we investigated if our observation was also relevant to a neurone‐like model. Abnormal Tau phosphorylation was detected in mitotic human neuroblastoma SY5Y cells overexpressing Tau. Regarding AT100‐immunoreactivity and phospho‐Ser422, we suggest that phosphatase 2A inhibition and a phosphorylation combination of mitotic kinases may lead to this Alzheimer‐type phosphorylation. Our results not only demonstrate the involvement of mitotic kinases in Alzheimer‐type Tau phosphorylation but also indicate that Xenopus oocyte could be a useful model to identify the kinases involved in this process.
Oligodendrocyte‐myelin glycoprotein (OMgp) is an inhibitor of neurite outgrowth
Authors: Kottis Vicky , Thibault Pierre , Mikol Daniel , Xiao Zhi‐Cheng , Zhang Rulin , Dergham Pauline , Braun Peter E. 
Published: March 2003

AbstractA protein fraction purified from bovine brain myelin, previously called arretin because of its ability to inhibit neurite outgrowth, has been identified as consisting predominantly of oligodendrocyte‐myelin glycoprotein (OMgp). We show that it is a potent inhibitor of neurite outgrowth from rat cerebellar granule and hippocampal cells; from dorsal root ganglion explants in which growth cone collapse was observed; from rat retinal ganglion neurons; and from NG108 and PC12 cells. OMgp purified by a different procedure from both mouse and human myelin behaves identically in all bioassays tested.
Neuronal oxidative damage from activated innate immunity is EP2 receptor‐dependent
Authors: Montine Thomas J. , Milatovic Dejan , Gupta Ramesh C. , Valyi‐Nagy Tibor , Morrow Jason D. , Breyer Richard M. 
Published: March 2003

AbstractIncrease in prostaglandin (PG) E2 levels and oxidative damage are associated with diseases of brain that involve activation of innate immunity. We tested the hypothesis that cerebral oxidative damage resulting from activation of innate immunity with intracerebroventricular (icv) lipopolysaccharide (LPS) is dependent on PGE2‐mediated signaling. We measured two quantitative in vivo biomarkers of lipid peroxidation: F2‐isoprostanes (IsoPs) that derive from arachidonic acid (AA) that is uniformly distributed in all cell types in brain, and F4‐neuroprostanes (NeuroPs) that derive from docosahexaenoic acid (DHA) that is highly concentrated in neuronal membranes. LPS stimulated delayed elevations in cerebral F2‐IsoPs and F4‐NeuroPs that were completely suppressed by indomethacin or ibuprofen pre‐treatment. LPS‐induced cerebral oxidative damage was abolished by disruption of subtype 2 receptor for PGE2 (EP2). In contrast, initial oxidative damage from icv kainic acid (KA) was more rapid than with LPS also was completely suppressed by indomethacin or ibuprofen pre‐treatment but was independent of EP2 receptor activation. The protective effect of deleting the EP2 receptor was not associated with changes in cerebral eicosaniod production, but was partially related to reduced induction of nitric oxide synthase (NOS) activity. These results suggest the EP2 receptor as a therapeutic target to limit oxidative damage from activation of innate immunity in cerebrum.
Polyethylene glycol immediately repairs neuronal membranes and inhibits free radical production after acute spinal cord injury
Authors: Luo Jian , Borgens Richard , Shi Riyi 
Published: March 2003

AbstractMembrane disruption and the production of reactive oxygen species (ROS) are important factors causing immediate functional loss, progressive degeneration, and death in neurons and their processes after traumatic spinal cord injury. Using an in vitro guinea pig spinal cord injury model, we have shown that polyethylene glycol (PEG), a hydrophilic polymer, can significantly accelerate and enhance the membrane resealing process to restore membrane integrity following controlled compression. As a result of PEG treatment, injury‐induced ROS elevation and lipid peroxidation (LPO) levels were significantly suppressed. We further show that PEG is not an effective free radical scavenger nor does it have the ability to suppress xanthine oxidase, a key enzyme in generating superoxide. These observations suggest that it is the PEG‐mediated membrane repair that leads to ROS and LPO inhibition. Furthermore, our data also imply an important causal effect of membrane disruption in generating ROS in spinal cord injury, suggesting membrane repair to be an effective target in reducing ROS genesis.
Effect of single and repeated methamphetamine treatment on neurotransmitter release in substantia nigra and neostriatum of the rat
Authors: Bustamante Diego , You Zhi‐Bing , Castel Marie‐Noëlle , Johansson Sara , Goiny Michel , Terenius Lars , Hökfelt Tomas , Herrera‐Marschitz Mario 
Published: March 2003

AbstractThe main purpose of this study was to characterize the initial neurotransmission cascade elicited by methamphetamine, analysing simultaneously with in vivo microdialysis monoamine, amino acid and neuropeptide release in substantia nigra and neostriatum of the rat. The main effect of a single systemic dose of methamphetamine (15 mg/kg, subcutaneously) was an increase in dopamine levels, both in substantia nigra (≈ 10‐fold) and neostriatum (≈ 40‐fold), accompanied by a significant, but lesser, increase in dynorphin B (≈ two‐fold, in both regions), and a decrease in monoamine metabolites. A similar effect was also observed after local administration of methamphetamine (100 µm) via the microdialysis probes, but restricted to the treated region. In other experiments, rats were repeatedly treated with methamphetamine or saline, with the last dose administered 12 h before microdialysis. Dopamine K+‐stimulated release was decreased following repeated methamphetamine administration compared with that following saline, both in the substantia nigra (by ≈ 65%) and neostriatum (by ≈ 20%). In contrast, the effect of K+‐depolarization on glutamate, aspartate and GABA levels was increased following repeated administration of methamphetamine. In conclusion, apart from an impairment of monoamine neurotransmission, repeated methamphetamine produces changes in amino acid homeostasis, probably leading to NMDA‐receptor overstimulation.