bluuebunny/crossref_metadata_2025_split huggingface dataset:
Basal hymenomycetes belonging to the Sebacinaceae are ectomycorrhizal on temperate deciduous trees
Authors: Selosse M.‐A. , Bauer R. , Moyersoen B. 
Published: March 2003

Summary• Heterobasidiomycetous species of the Sebacinaceae family, previously considered as saprophytes or parasites, are shown here to form ectomycorrhizas on temperate forest trees.• Ectomycorrhizas were collected under sebacinoid sporophores and near root systems of Neottia nidus‐avis, an orchid symbiotic with sebacinoids. To identify the partners each ectomycorrhiza was submitted to amplification and sequencing of the plant and fungal internal transcribed spacer (ITS), and further investigated by light and electron microscopy whenever a sebacinoid ITS was found.• Molecular and microscopic analyses correlated well. Two sebacinoids of divergent rDNA sequences were demonstrated to form similar ectomycorrhizas, with a well‐developed Hartig net and a hyphal mantle having thick‐walled outer mantle hyphae. The ultrastructure of the septal pore (dolipore with imperforate caps) was typical for sebacinoids. In one case, intracellular colonization was seen. The ectomycorrhizal host range of these sebacinoids was not specific and included Betulaceae, Fagaceae and Tiliaceae.• Sebacinoids probably represent an overlooked ectomycorrhizal group and ectomycorrhizal symbiosis may be common among basal lineages of hymenomycetes.
Nuclear factor κB is a critical determinant in N‐methyl‐d‐aspartate receptor‐mediated neuroprotection
Authors: Lipsky Robert H. , Xu Ke , Zhu Daming , Kelly Charles , Terhakopian Artin , Novelli Antonello , Marini Ann M. 
Published: March 2003

The role of a nuclear factor κB (NF‐κB) in NMDA receptor‐mediated neuroprotection is not known. A candidate sequence from the 5′ flanking region of exon 3 of the rat brain‐derived neurotrophic factor (BDNF) gene was used to show that exposure of rat cerebellar granule cells to 100 μm NMDA activated a specific DNA binding activity that was blocked by the NMDA receptor antagonist MK‐801. Anti‐p65 antibody or anti‐p50 antibody ‘supershifted’ the DNA binding activity, suggesting that the DNA–protein complex was composed of p65 and p50 subunits. NMDA receptor‐mediated neuroprotection was blocked when cerebellar neurons were transfected with a double‐stranded oligonucleotide containing the BDNF gene NF‐κB sequence. Furthermore, nuclear extracts prepared from neurons treated with NMDA and the double‐stranded NF‐κB oligonucleotide showed reduced DNA binding activity to the target sequence, supporting the idea that NF‐κB may be involved in the transcriptional activation of the BDNF gene. To address this issue, we quantified the level of exon 3‐specific BDNF mRNA. Relative to GAPDH mRNA levels and compared with untreated neurons, NMDA increased exon 3‐specific BDNF mRNA twofold. In contrast, pretreatment of neurons with the NF‐κB target DNA abolished the increase in BDNF mRNA following addition of NMDA. We also determined that BDNF itself induced an NF‐κB DNA binding activity. Taken together, these data support a mechanism where NF‐κB plays a critical role in NMDA‐mediated neuroprotection.
Different action on dopamine catabolic pathways of two endogenous 1,2,3,4‐tetrahydroisoquinolines with similar antidopaminergic properties
Authors: Antkiewicz‐Michaluk Lucyna , Michaluk Jerzy , Mokrosz Maria , Romanska Irena , Lorenc‐Koci Elbieta , Ohta Shigeru , Vetulani Jerzy 
Published: March 2003

The effect of single and multiple 1‐methyl‐1,2,3,4‐tetrahydroisoquinoline (1MeTIQ) and 1‐benzyl‐1,2,3,4‐tetrahydroisoquinoline (1BnTIQ) administration on concentrations of dopamine and its metabolites: homovanillic acid (HVA) and 3,4‐dihydroxyphenylacetic acid (DOPAC) and 3‐methoxytyramine (3MT) in three brain areas was studied HPLC with electrochemical detection in Wistar rats. The rate of dopamine catabolism in the striatum along the N‐oxidative and O‐methylation pathways was assessed by calculation of the ratio of appropriate metabolites to dopamine concentration. In addition, the spontaneous and apomorphine‐stimulated locomotor activity, and muscle rigidity was studied after acute administration of 1MeTIQ and 1BnTIQ. We have found that 1MeTIQ did not change the level of dopamine and HVA in all investigated structures both after a single and chronic administration. However, the levels of intermediary dopamine metabolites, DOPAC and 3MT, were distinctly affected. The level of DOPAC was strongly depressed (by 60–70%) while the level of extraneuronal matabolite 3MT was significantly elevated (by 170–200%). In contrast to 1MeTIQ, 1BnTIQ depressed the level of dopamine (by approximately 60%) and increased the level of total metabolite, HVA, (by 40%) especially in the striatum, but the levels of DOPAC and 3MT remained unchanged. The paper has shown that 1MeTIQ and 1BnTIQ produced different effects on dopamine catabolism. Potential neuroprotective compound 1MeTIQ did not change the rate of total dopamine catabolism, it strongly inhibited the monoamine oxidase (MAO)‐dependent catabolic pathway and significantly activated the catechol‐O‐methyltransferase (COMT)‐dependent O‐methylation. In contrast 1BnTIQ, a compound with potential neurotoxic activity, produced the significant increase of the rate of dopamine metabolism with strong activation of the oxidative MAO‐dependent catabolic pathway. Interestingly, both compounds produced similar antidopaminergic functional effects: antagonism of apomorphine hyperactivity and induction of muscle rigidity. The results may explain the biochemical basis of the neuroprotective and of the neurotoxic properties endogenous brain tetrahydroisoquinoline derivatives.
Role of polyamine metabolism in kainic acid excitotoxicity in organotypic hippocampal slice cultures
Authors: Liu Wei , Liu Ruolan , Schreiber Steve S. , Baudry Michel 
Published: March 2003

Polyamines are ubiquitous cations that are essential for cell growth, regeneration and differentiation. Increases in polyamine metabolism have been implicated in several neuropathological conditions, including excitotoxicity. However, the precise role of polyamines in neuronal degeneration is still unclear. To investigate mechanisms by which polyamines could contribute to excitotoxic neuronal death, the present study examined the role of the polyamine interconversion pathway in kainic acid (KA) neurotoxicity using organotypic hippocampal slice cultures. Treatment of cultures with N1,N(2)‐bis(2,3‐butadienyl)‐1,4‐butanediamine (MDL 72527), an irreversible inhibitor of polyamine oxidase, resulted in a partial but significant neuronal protection, especially in CA1 region. In addition, this pre‐treatment also attenuated KA‐induced increase in levels of lipid peroxidation, cytosolic cytochrome C release and glial cell activation. Furthermore, pre‐treatment with a combination of cyclosporin A (an inhibitor of the mitochondrial permeability transition pore) and MDL 72527 resulted in an additive and almost total neuronal protection against KA toxicity, while the combination of MDL 72527 and EUK‐134 (a synthetic catalase/superoxide dismutase mimetic) did not provide additive protection. These data strongly suggest that the polyamine interconversion pathway partially contributes to KA‐induced neurodegeneration via the production of reactive oxygen species.
Overexpression of manganese superoxide dismutase attenuates neuronal death in human cells expressing mutant (G37R) Cu/Zn‐superoxide dismutase
Authors: Flanagan Shawn W. , Anderson Richard D. , Ross Mark A. , Oberley Larry W. 
Published: March 2003

AbstractAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of motor function and eventual death as a result of degeneration of motor neurons in the spinal cord and brain. The discovery of mutations in SOD1, the gene encoding the antioxidant enzyme Cu/Zn‐superoxide dismutase (CuZnSOD), in a subset of ALS patients has led to new insight into the pathophysiology of ALS. Utilizing a novel adenovirus gene delivery system, our laboratory has developed a human cell culture model using chemically differentiated neuroblastoma cells to investigate how mutations in SOD1 lead to neuronal death. Expression of mutant SOD1 (G37R) resulted in a time and dose‐related death of differentiated neuroblastoma cells. This cell death was inhibited by overexpression of the antioxidant enzyme manganese superoxide dismutase (MnSOD). These observations support the hypothesis that mutant SOD1‐ associated neuronal death is associated with alterations in oxidative stress, and since MnSOD is a mitochondrial enzyme, suggest that mitochondria play a key role in disease pathogenesis. Our findings in this model of inhibition of mutant SOD1‐associated death by MnSOD represent an unique approach to explore the underlying mechanisms of mutant SOD1 cytotoxicity and can be used to identify potential therapeutic agents for further testing.
Altered glycosylation of acetylcholinesterase in APP (SW) Tg2576 transgenic mice occurs prior to amyloid plaque deposition
Authors: Fodero Lisa R. , Sáez‐Valero Javier , McLean Catriona A. , Martins Ralph N. , Beyreuther Konrad , Masters Colin L. , Terry A. Robertson  , Small David H. 
Published: March 2003

AbstractPrevious studies have shown that a minor glycoform of acetylcholinesterase (AChE) is increased in Alzheimer's disease brain and cerebrospinal fluid. This glycoform can be distinguished from other AChE species by its lack of binding to concanavalin A (Con A). In this study, the temporal relationship between AChE glycosylation and Aβ deposition was examined in Tg2576 mice. There was a significant (p < 0.05) difference in AChE glycosylation in Tg2576 mice compared with age‐matched background strain control mice at 4 months of age. This difference in glycosylation was also observed in 8‐ and 12‐month‐old Tg2576 mice. In contrast, Aβ plaques were only seen in the Tg2576 mice at 12 months of age, and were not detected at 4 and 8 months of age. Soluble human‐sequence Aβ was detected as early as 4 months of age in the transgenic mice. The altered AChE glycosylation was due to an increase in a minor AChE isoform, which did not bind Con A, similar to that previously observed to be increased in Alzheimer's disease brain and cerebrospinal fluid. The results demonstrate that in transgenic mice altered AChE glycosylation is associated with very early events in the development of AD‐like pathology. The study supports the possibility that glycosylation may also be a useful biomarker of AD.
Expression and characterization of the Drosophila X11‐like/Mint protein during neural development
Authors: Hase Momoko , Yagi Yoshimasa , Taru Hidenori , Tomita Susumu , Sumioka Akio , Hori Kazuya , Miyamoto Kanako , Sasamura Takeshi , Nakamura Makoto , Matsuno Kenji , Suzuki Toshiharu 
Published: March 2003

AbstractThe X11‐like (X11L) protein was originally isolated as a protein bound to the cytoplasmic domain of the β‐amyloid precursor protein (APP), which is associated with Alzheimer's disease. In mammals, X11L is believed to play an important role in the regulation of APP metabolism. Here we isolated and characterized the Drosophila X11L (dX11L) protein, also may be referred to this protein as Drosophila Mint (dMint), Lin 10 (dLin10) or X11 (dX11), is thought to be expressed in neuronal tissues from late embryonic through to the adult stages of the fly. The phosphotyrosine interaction domain of dX11L interacts with the cytoplasmic domain of the Drosophila amyloid precursor protein‐like (APPL) similar to the way human X11L (hX11L) interacts with APP. Overexpression of dX11L on post‐mitotic neurons had a lethal effect on flies and, when it was localized to the eye imaginal disc, disruption of compound eye morphology due to enhanced apoptosis of neuronal cells was observed. Overexpression of hX11L and the PDZ domain of dX11L resulted in identical eye phenotypes. The PDZ domain is highly conserved between Drosophila and human, and appears to be responsible for this phenotype. Our findings suggest that the X11L family may be involved with the regulation of apoptosis during neural cell development and that aberrant X11L function could be contribute in this way to the neuronal degeneration observed in Alzheimer's disease.
Altered arachidonic acid biosynthesis and antioxidant protection mechanisms in Schwann cells grown in elevated glucose
Authors: Mîinea Cristinel , Kuruvilla Rejji , Merrikh Houra , Eichberg Joseph 
Published: March 2003

AbstractIn cultured Schwann cells, elevated glucose induces alterations in arachidonic acid metabolism that cause a decrease in the content of glycerophospholipid arachidonoyl‐containing molecular species (ACMS). This could result from decreased de novo arachidonic acid biosynthesis, or increased arachidonic acid release from phospholipids. Incorporation of radioactive 8,11,14‐eicosatrienoic acid into ACMS was lower for cells grown in 30 mm versus 5 mm glucose, consistent with a decrease in Δ5 desaturase activity. However, neither basal arachidonic acid release from prelabeled cells nor stimulated generation of arachidonic acid in the presence of the reacylation inhibitor, thimerosal, the phosphotyrosine phosphatase inhibitor, bipyridyl peroxovanadium, or both together, were altered by varying the glucose concentrations, indicating that arachidonic acid turnover did not contribute to ACMS depletion. Free cytosolic NAD+/NADH decreased, whereas NADP+/NADPH remained unchanged for cells grown in elevated glucose, implying that decreased desaturase activity is a result of metabolic changes other than cofactor availability. Schwann cells in elevated glucose were susceptible to oxidative stress, as shown by increased malondialdehyde, depleted glutathione levels, and reduced cytosolic superoxide dismutase activity. Glutathione‐altering compounds had no effect on ACMS levels, in contrast to N‐acetylcysteine and α‐lipoic acid, which partly corrected ACMS depletion in phosphatidylcholine. These findings suggest that in the Schwann cell cultures, a high glucose level elicits oxidative stress and weakens antioxidant protection mechanisms which could decrease arachidonic acid biosynthesis and that this deficit can be partly corrected by treatment with exogenous antioxidants.
Agonists activate Gi1α or Gi2α fused to the human mu opioid receptor differently
Authors: Massotte Dominique , Brillet Karl , Kieffer Brigitte , Milligan Graeme 
Published: March 2003

AbstractAs preferential coupling of opioid receptor to various inhibitory Gα subunits is still under debate, we have investigated the selectivity of the human mu opioid receptor fused to a pertussis toxin insensitive C351I Gi1α or C352I Gi2α in stably transfected HEK 293 cells. Overall agonist binding affinities were increased for both fusion constructs when compared to the wild type receptor. [35S]GTPγS binding was performed on pertussis toxin treated cells to monitor coupling efficiency of the fusion constructs. Upon agonist addition hMOR‐C351I Gi1a exhibited an activation profile similar to the non‐fused receptor while hMOR‐C352I Gi2α was poorly activated. Interestingly no correlation could be drawn between agonist binding affinity and efficacy. Upon agonist addition, forskolin‐stimulated cAMP production, as measured using a reporter gene assay, was inhibited by signals transduced via the fused Gi1α and Gi2α mainly. In contrast both fusion constructs were able to initiate ERK‐MAPK phosphorylation via coupling to endogenous G proteins only. In conclusion our data indicate that hMOR couples more efficiently to Gi1α than Gi2α and that the coupling efficacy is clearly agonist‐dependent.
Alterations in metabolism and gene expression in brain regions during cuprizone‐induced demyelination and remyelination
Authors: Jurevics Helga , Largent Carrie , Hostettler Janell , Sammond Deanne W. , K. Matsushima Glenn ,   Amber Kleindienst,, Toews Arrel D. , Morell Pierre 
Published: March 2003

AbstractExposure of mice to the copper chelator, cuprizone, results in CNS demyelination. There is remyelination after removal of the metabolic insult. We present brain regional studies identifying corpus callosum as particularly severely affected; 65% of cerebroside is lost after 6 weeks of exposure. We examined recovery of cerebroside and ability to synthesize cerebroside and cholesterol following removal of the toxicant. The temporal pattern for concentration of myelin basic protein resembled that of cerebroside. We applied Affymetrix GeneChip technology to corpus callosum to identify temporal changes in levels of mRNAs during demyelination and remyelination. Genes coding for myelin structural components were greatly down‐regulated during demyelination and up‐regulated during remyelination. Genes related to microglia/macrophages appeared in a time‐course (peaking at 6 weeks) correlating with phagocytosis of myelin and repair of lesions. mRNAs coding for many cytokines had peak expression at 4 weeks, compatible with intercellular signaling roles. Of interest were other genes with temporal patterns correlating with one of the three above patterns, but of function not obviously related to demyelination/remyelination. The ability to correlate gene expression with known pathophysiological events should help in elucidating further function of such genes as related to demyelination/remyelination.
Cerebral dicarboxylate transport and metabolism studied with isotopically labelled fumarate, malate and malonate
Authors: Hassel Bjørnar , Bråthe Anders , Petersen Dirk 
Published: March 2003

AbstractTransport and metabolism of dicarboxylates may be important in the glial‐neuronal metabolic interplay. Further, exogenous dicarboxylates have been suggested as cerebral energy substrates. After intrastriatal injection of [14C]fumarate or [14C]malate, glutamine attained a specific activity 4.1 and 2.6 times higher than that of glutamate, respectively, indicating predominantly glial uptake of these four‐carbon dicarboxylates. In contrast, the three‐carbon dicarboxylate [14C]malonate gave a specific activity in glutamate which was approximately five times higher than that of glutamine, indicating neuronal uptake of malonate. Therefore, neurones and glia take up different types of dicarboxylates, probably by different transport mechanisms. Labelling of alanine from [14C]fumarate and [14C]malate demonstrated extensive malate decarboxylation, presumably in glia. Intravenous injection of 75 µmol [U‐13C]fumarate rapidly led to high concentrations of [U‐13C]fumarate and [U‐13C]malate in serum, but neither substrate labelled cerebral metabolites as determined by 13C NMR spectroscopy. Only after conversion of [U‐13C]fumarate into serum glucose was there 13C‐labelling of cerebral metabolites, and only at <10% of that obtained with 75 µmol [3‐13C]lactate or [2‐13C]acetate. These findings suggest a very low transport capacity for four‐carbon dicarboxylates across the blood–brain barrier and rule out a role for exogenous fumarate as a cerebral energy substrate.
Role of the 5′ untranslated region (UTR) in the tissue‐specific regulation of rat tryptophan hydroxylase gene expression by stress
Authors: Chamas Firas , Sabban Esther L. 
Published: March 2003

AbstractThere are tissue specific discrepancies in expression of tryptophan hydroxylase (TPH) between the pineal gland and brainstem. TPH mRNA levels in the pineal are much higher than in the brainstem, however, the two tissues contain comparable protein levels. This discrepancy could result from different translation efficiency of two of the TPH mRNA isoforms. Using PCR‐based methods, we analyzed the relative expression, in pineal and brainstem, of two TPH mRNA isoforms differing in the length of their untranslated region (5′UTR). The levels of the TPHα were found to be 960‐fold more abundant than the 51‐nucleotide longer TPHβ, in the pineal. TPHβ was also detected for the first time in the brainstem, where TPHβ/TPHα was about five‐fold higher than in the pineal. To study the role of the different 5′UTRs, each was cloned in‐frame upstream of luciferase, and transfected into PC12 cells. Both 5′UTRs enhanced luciferase activity, with TPHβ 5′UTR being more effective than TPHα 5′UTR, indicating selective regulation of translation efficiency. We also examined whether physiological manipulations alter the distribution of the TPH mRNA isoforms. Repeated stress had no effect in pineal, but led to a marked preferential induction of TPHβ in brainstem. Modulation of TPH gene expression in serotonergic neurons could result from selective and tissue specific regulation of its mRNA isoforms.
Activation of stress signaling molecules in bat brain during arousal from hibernation
Authors: Lee Moonyong , Choi Inho , Park Kyoungsook 
Published: March 2003

AbstractInduction of glucose‐regulated proteins (GRPs) is a ubiquitous intracellular response to stresses such as hypoxia, glucose starvation and acidosis. The induction of GRPs offers some protection against these stressesin vitro, but the specific role of GRPsin vivoremains unclear. Hibernating bats present a goodin vivomodel to address this question. The bats must overcome local high oxygen demand in tissue by severe metabolic stress during arousal thermogenesis. We used brain tissue of a temperate batRhinolopus ferrumequinumto investigate GRP induction by high metabolic oxygen demand and to identify associated signaling molecules. We found that during 30 min of arousal, oxygen consumption increased from nearly zero to 11.9/kg/h, which was about 8.7‐fold higher than its active resting metabolic rate. During this time, body temperature rose from 7°C to 35°C, and levels of TNF‐α and lactate in brain tissue increased 2–2.5‐fold, indicating a high risk of oxygen shortage. Concomitantly, levels of GRP75, GRP78 and GRP94 increased 1.5–1.7‐fold. At the same time, c‐Jun N‐terminal protein kinase (JNK) activity increased 6.4‐fold, and extracellular signal‐regulated protein kinase (ERK) activity decreased to a similar degree (6.1‐fold). p38 MAPK activity was very low and remained unchanged during arousal. In addition, survival signaling molecules protein kinase B (Akt) and protein kinase C (PKC) were activated 3‐ and 5‐fold, respectively, during arousal. Taken together, our results showed that bat brain undergoes high oxygen demand during arousal from hibernation. Up‐regulation of GRP proteins and activation of JNK, PKCγ and Akt may be critical for neuroprotection and the survival of bats during the repeated process.
Calcium/calmodulin‐dependent kinase II phosphorylation of the GABAA receptor α1 subunit modulates benzodiazepine binding
Authors: Churn Severn B. , Rana Aniruddha , Lee Kangmin , Parsons J. Travis , De Blas Angel , Delorenzo Robert J. 
Published: March 2003

Abstractγ‐Aminobutyric acid (GABA) is the primary neurotransmitter that is responsible for the fast inhibitory synaptic transmission in the central nervous system. A major post‐translational mechanism that can rapidly regulate GABAAR function is receptor phosphorylation. This study was designed to test the effect of endogenous calcium and calmodulin‐dependent kinase II (CaM kinase II) activation on both allosteric modulator binding and GABAA receptor subunit phosphorylation. Endogenous CaM kinase II activity was stimulated, and GABAA receptors were subsequently analyzed for bothallosteric modulator binding properties and immunoprecipitated and analyzed for subunit phosphorylation levels. A significant increase in allosteric‐modulator binding of the GABAAR was observed under conditions maximal for CaM kinase II activation. In addition, CaM kinase II activation resulted in a direct increase in phosphorylation of the GABAA receptor α1 subunit. The data suggest that the CaM kinase II‐dependent phosphorylation of the GABAA receptor α1 subunit modulated allosteric modulator binding to the GABAA receptor.