bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ammonia induces the mitochondrial permeability transition in primary cultures of rat astrocytes
Authors: Bai G. , Rama Rao K.V. , Murthy Ch.R.K. , Panickar K.S. , Jayakumar A.R. , Norenberg M.D. 
Published: August 2002

AbstractAmmonia is a toxin that has been strongly implicated in the pathogenesis of hepatic encephalopathy (HE), and the astrocyte appears to be the principal target of ammonia toxicity. The specific neurochemical mechanisms underlying HE, however, remain elusive. One of the suggested mechanisms for ammonia toxicity is impaired cellular bioenergetics. Because there is evidence that the mitochondrial permeability transition (MPT) is associated with mitochondrial dysfunction, we determined whether the MPT might be involved in the bioenergetic alterations related to ammonia toxicity. Accordingly, we examined the mitochondrial membrane potential (Δψm) in cultured astrocytes and neurons using laser‐scanning confocal microscopy after loading the cells with the voltage‐sensitive dye JC‐1. We found that ammonia induced a dissipation of the Δψmin a time‐ and concentration‐dependent manner. These findings were supported by flow cytometry using the voltage‐sensitive dye tetramethylrhodamine ethyl ester (TMRE). Cyclosporin A, a specific inhibitor of the MPT, completely blocked the ammonia‐induced dissipation of the Δψm. We also found an increase in the mitochondrial permeability to 2‐deoxyglucose in astrocytes that had been exposed to 5 mM NH4Cl, further supporting the concept that ammonia induces the MPT in these cells. Pretreatment with methionine sulfoximine, an inhibitor of glutamine synthetase, blocked the ammonia‐induced collapse of Δψm, suggesting a role of glutamine in this process. Over a 24‐hr period, ammonia had no effect on the Δψmin cultured neurons. Collectively, our data indicate that ammonia induces the MPT in cultured astrocytes, which may be a factor in the mitochondrial dysfunction associated with HE and other hyperammonemic states. © 2001 Wiley‐Liss, Inc.
Glucose and lactate metabolism during brain activation
Authors: Dienel Gerald A. , Hertz Leif 
Published: August 2002

AbstractThe dependence of brain function on blood glucose as a fuel does not exclude the possibility that lactate within the brain might be transferred between different cell types and serve as an energy source. It has been recently suggested that 1) about 85% of glucose consumption during brain activation is initiated by aerobic glycolysis in astrocytes, triggered by demand for glycolytically derived energy for Na+‐dependent accumulation of transmitter glutamate and its amidation to glutamine, and 2) the generated lactate is quantitatively transferred to neurons for oxidative degradation. However, astrocytic glutamate uptake can be fuelled by either glycolytically or oxidatively derived energy, and the extent to which “metabolic trafficking” of lactate might occur during brain function is unknown. In this review, the potential for an astrocytic–neuronal lactate flux has been estimated by comparing rates of glucose utilization in brain and in cultured neurons and astrocytes with those for lactate release and uptake. Working brain tissue and isolated brain cells release large amounts of lactate. Cellular lactate uptake occurs by carrier‐mediated facilitated diffusion and is normally limited by its dependence on metabolism of accumulated lactate to maintain a concentration gradient. The rate of this process is similar in cultured astrocytes and glutamatergic neurons, and, at physiologically occurring lactate concentrations, lactate uptake corresponds at most to 25% of the rate of glucose oxidation, which accordingly is the upper limit for “metabolic trafficking” of lactate. Because of a larger local release than uptake of lactate and the necessity for rapid lactate clearance to maintain the intracellular redox state to support lactate production in the presence of normal oxygen levels, brain activation in vivo is probably, in many cases, accompanied by a substantial overflow of glycolytically generated lactate, both to different brain areas and under some conditions (spreading depression, hyperammonemia) to circulating blood. © 2001 Wiley‐Liss, Inc.
Pharmacodynamics of citicoline relevant to the treatment of glaucoma
Authors: Grieb Pawel , Rejdak Robert 
Published: August 2002

AbstractCiticoline (exogenous CDP‐choline) is a nontoxic and well‐tolerated drug used in pharmacotherapy of brain insufficiency and some other neurological disorders, such as stroke, brain trauma, and Parkinson's disease. A few reports indicate that citicoline treatment may also be beneficial in glaucoma. Currently glaucoma is considered a neurodegenerative disease in which retinal ganglion cells (RGC) slowly die, likely in the apoptotic mechanism. Endogenous CDP‐choline is a natural precursor of cellular synthesis of phospholipids, mainly phosphatydylcholine (PtdCho). Enhancement of PtdCho synthesis may counteract neuronal apoptosis and provide neuroprotection. Citicoline, when administered, undergoes a quick transformation to cytidine and choline, which are believed to enter brain cells separately and provide neuroprotection by enhancing PtdCho synthesis; similar effect may be expected to occur in glaucomatous RGC. Furthermore, citicoline stimulates some brain neurotransmitter systems, including the dopaminergic system, and dopamine is known as a major neurotransmitter in retina and postretinal visual pathways. In a double‐blind, placebo‐controlled study, treatment of glaucoma resulted in functional improvement in the visual system noted with electrophysiological methods. Development of citicoline as a treatment for glaucoma is indicated. © 2002 Wiley‐Liss, Inc.
Plasma melatonin, pinealocyte morphology, and surface receptors/antigen expression on macrophages/microglia in the pineal gland following a high‐altitude exposure
Authors: Kaur C. , Srinivasan K.N. , Singh J. , Peng C.M. , Ling E.A. 
Published: August 2002

AbstractThe present study examined the effects of high‐altitude exposure on the pineal gland, the main source of production of melatonin. It was surmised that hypoxia experienced at high altitude, caused by decreased oxygen tension in the ambient air, might lead to some structural alterations in the pineal gland and, hence, affect its melatonin production. Adult Wistar rats were exposed to an altitude of 8,000 m for 2 hr in an altitude chamber and then sacrificed at various time intervals after the exposure. Normal rats kept at ground level were used as controls. Blood samples were collected at various time intervals for measurement of plasma melatonin level, and the pineal glands from both groups were processed for electron microscopy and immunohistochemistry. The plasma melatonin level showed a steady increase following altitude exposure peaking at 7 days and returned to control levels thereafter. Between 1 and 4 days after altitude exposure, the mitochondrial number and lipid droplets in the pinealocytes appeared to be reduced compared with those in control rats. At 7 days, however, the mitochondrial numbers and lipid droplets were noticeably increased. At the same time interval, the expression of complement type 3 receptors and major histocompatibility class II antigens as detected with the antibodies OX‐42 and OX‐6, respectively, in macrophages/microglia was up‐regulated compared with that in the control rats and those killed at earlier times. This was attributed to the increased serum melatonin after the altitude exposure. By 14 and 21 days, the ultrastructure of pinealocytes and immunoreactivity of macrophages/microglia were comparable with those in the control rats. We conclude from this study that an altitude exposure in rats leads to an increase in melatonin production, which returned to control levels with passage of time. © 2002 Wiley‐Liss, Inc.
Timing the doxycycline yields different patterns of genomic recombination in brain neurons with a new inducible Cre transgene
Authors: Lindeberg J̇onas , Mattsson Ragnar , Ebendal Ted 
Published: August 2002

AbstractWe have developed a transgenic mouse expressing the Cre recombinase under control of a tetracycline‐responsive promoter. Using a CamKIIα‐driven tTA transgenic strain and a lacZ reporter mouse, we obtained the expected neuronal pattern of recombination in the olfactory lobe, cortex, striatum, hippocampus and Purkinje cells. Moreover, recombination can be completely abolished by feeding the mice doxycycline in their drinking water. We also show that it is possible to get a different pattern of recombination by changing the timing of the doxycycline‐mediated shutdown of Cre expression. By starting the doxycycline treatment at birth, we restrict recombination to striatum only. This approach should be applicable to other inducible transgenic strains, thus increasing the number of available tissue‐specific patterns for conditional knockouts. Also, our tetO‐Cre transgene can be combined with any of the increasing number of tetracycline transactivator transgenic strains to direct specifically inducible genomic recombination to several areas of the brain. © 2002 Wiley‐Liss, Inc.
Recovery of deficient cholinergic calcium signaling by adenosine in cultured rat cortical astrocytes
Authors: Ferroni Stefano , Marchini Cristina , Ogata Tadanori , Schubert Peter 
Published: August 2002

AbstractThe regulation of the cholinergic calcium signaling in astroglial cells is thought to play a crucial role in the pathogenesis of Alzheimer's disease. We investigated the action of the cell modulator adenosine on acetylcholine (Ach)‐mediated intracellular calcium ([Ca2+]i) transients in cultured rat cortical astrocytes using the Ca2+ imaging technique. The stable adenosine analog 2‐chloroadenosine (2ClA) potentiated the [Ca2+]i rise induced by activation of muscarinic Ach receptors by shifting ∼30‐fold the half‐effective Ach concentration. This 2ClA effect was maintained upon removal of extracellular Ca2+, indicating that Ach‐induced [Ca2+]i elevation was due mainly to Ca2+ mobilization from intracellular stores. Pharmacological studies demonstrated that the 2ClA action was mediated by A1 receptors. Incubation with pertussis toxin abrogated the 2ClA effect but left unchanged the [Ca2+]i rise produced by Ach alone. The [Ca2+]i response elicited by Ach alone was abolished upon blockade of muscarinic receptor subtypes that stimulate phospholipase C, whereas the [Ca2+]i elevation generated by the combined action of subthreshold Ach and 2ClA was not affected. Collectively, these results suggest that the impaired cholinergic signaling, the cardinal symptom of Alzheimer's disease, can be reinforced at the second messenger level by an alternative intracellular Ca2+ mobilizing path, which can be brought into play by the concomitant activation of A1 purinoceptors and muscarinic receptors negatively coupled to adenylyl cyclase. © 2002 Wiley‐Liss, Inc.
Identification of the amino acids on a neuronal glutamate receptor recognized by an autoantibody from a patient with paraneoplastic syndrome
Authors: Carlson Noel G. , Gahring Lorise C. , Rogers Scott W. 
Published: August 2002

AbstractAutoantibodies from a patient with paraneoplastic disease were identified previously to bind to the glutamate receptor (GluR) subunit GluR5 and to function as potential allosteric modulators of receptor activity (Gahring et al. [1995] Mol Med 1:245–253). In the present study we have used deletion mapping and mutagenesis to define the residues in GluR5 bound by this autoreactivity. The autoantibody contact residues include residues K497, N508, K510, E512, and to a lesser extent Q507. Residues 507–512 confer autoantibody specificity of the autoreactivity to GluR5. These residues have been shown in crystallographic studies (Armstrong et al. [1998] Nature 395:913–917) to participate in a loop structure, whereas residue K497 is located on a beta‐strand. Notably, this binding spans tyrosine 504, a residue important in forming the agonist‐binding site. We propose that autoantibody binding of essential residues in this GluR5 autoantigenic region defines a subunit‐specific allosteric regulatory site on neuronal glutamate receptors and suggests how receptor dysfunction and region‐specific neuronal death in the brain can progress in certain autoimmune neurological diseases. J. Neurosci. Res. 63:480–485, 2001. © 2001 Wiley‐Liss, Inc.
Attenuation of malonate toxicity in primary mesencephalic cultures using the GABA transport blocker, NO‐711
Authors: Stokes Alan H. , Bernard Laura P. , Nicklas William J. , Zeevalk Gail D. 
Published: August 2002

AbstractCultured rat mesencephalic neurons were used to assess the effects of γ‐aminobutyric acid (GABA) transport blockers on toxicity caused by malonate, a reversible, competitive inhibitor of succinate dehydrogenase. Previous studies utilizing an ex vivo chick retinal preparation have shown that GABA release and cell swelling are early consequences of acute energy impairment and that GABA transport blockers attenuate this toxicity. The present results demonstrate that the nonsubstrate GABA transport blocker, NO‐711 (1 nM–1 μM), dose‐dependently protected cultured mesencephalic dopamine (DA) and GABA neurons from malonate‐induced toxicity. Similar protection was demonstrated with nipecotic acid (1 mM) and SKF89976A (100 nM), substrate and nonsubstrate GABA transport blockers, respectively. These compounds by themselves produced no signs of toxicity, although nipecotic acid caused a long‐term decrease in GABA uptake not associated with toxicity. Compounds which decrease intracellular reactive oxygen species (ROS) are protective in this model, but NO‐711 did not prevent the rise in intracellular ROS induced by malonate, indicating its protective effects were downstream of ROS production. Supplementation of malonate treated cultures with the GABAA agonist, muscimol (10 μM), increased the toxicity toward the DA and GABA neuron populations. Antagonists at the GABAA and glycine receptors provided partial protection to both the GABA and DA neurons. These findings suggest that the GABA transporter, GABAA, and/or glycine channels contribute to cell damage associated with energy impairment in this model. J. Neurosci. Res. 64:43–52, 2001. © 2001 Wiley‐Liss, Inc.
Purkinje cell degeneration in mice lacking the xeroderma pigmentosum group G gene
Authors: Sun Xue‐Zhi , Harada Yoshi‐Nobu , Takahashi Sentaro , Shiomi Naoko , Shiomi Tadahiro 
Published: August 2002

AbstractLaboratory mice carrying the nonfunctional xeroderma pigmentosum group G gene (the mouse counterpart of the human XPG gene) alleles have been generated by using gene‐targeting and embryonic stem cell technology. Homozygote animals of this autosomal recessive disease exhibited signs and symptoms, such as postnatal growth retardation, reduced levels of activity, progressive ataxia and premature death, similar to the clinical manifestations of Cockayne syndrome (CS). Histological analysis of the cerebellum revealed multiple pyknotic cells in the Purkinje cell layer of the xpg homozygotes, which had atrophic cell bodies and shrunken nuclei. Further examination by an immunohistochemistry for calbindin‐D 28k (CaBP) showed that a large number of immunoreactive Purkinje cells were atrophic and their dendritic trees were smaller and shorter than in wild‐type littermates. These results indicated a marked degeneration of Purkinje cells in the xpg mutant cerebellum. Study by in situ detection of DNA fragmentation in the cerebellar cortex demonstrated that some deoxynucleotidyl transferase (TdT)‐mediated dUTP‐biotin in situ nick labeling (TUNEL)‐positive cells appeared in the granule layer of the mutant mice, but few cell deaths were confirmed in the Purkinje layer. These results suggested Purkinje cell degeneration in the mutant cerebellum was underway, in which much Purkinje cell death had not appeared, and the appearance of some abnormal cerebellar symptoms in the xpg‐deficient mice was not only due to a marked Purkinje cell degeneration, but also to damage of other cells. J. Neurosci. Res. 64:348–354, 2001. © 2001 Wiley‐Liss, Inc.
tert‐Butylhydroperoxide induces peroxynitrite‐dependent mitochondrial permeability transition leading PC12 cells to necrosis
Authors: Palomba Letizia , Sestili Piero , Cantoni Orazio 
Published: August 2002

AbstractA short‐term exposure of PC12 cells to tert‐butylhydroperoxide, followed by recovery in fresh culture medium, causes cell death and the extent of this response progressively increases during the 120 min of post‐treatment incubation. Morphological and biochemical analyses of these cells revealed that the mode of cell death was necrosis. Cell killing induced by the hydroperoxide seems to be in part mediated by peroxynitrite because the lethal response was markedly and similarly reduced by the nitric oxide synthase inhibitor Nω‐nitro‐L‐arginine methylester and by scavengers of nitric oxide or peroxynitrite. This peroxynitrite‐dependent mechanism of cytotoxicity was blunted by antioxidants and inhibitors of mitochondrial permeability transition and the onset of cell death was preceded by mitochondrial depolarization and loss of cellular ATP. We conclude that tert‐butylhydroperoxide promotes peroxynitrite‐dependent PC12 cell necrosis causally linked to peroxidation of membrane lipids and mitochondrial permeability transition. J. Neurosci. Res. 65:387–395, 2001. © 2001 Wiley‐Liss, Inc.
Laminar variation in neuronal viability and trophic dependence in neocortical slices
Authors: Niblock Mary M. , Brunso‐Bechtold Judy K. , Riddle David R. 
Published: August 2002

AbstractOrganotypic slices are used frequently in studies of central nervous system development and function because they provide excellent experimental access with significant preservation of cellular context and relationships. Within a slice, however, a variety of factors may cause individual classes of neurons to respond differently to the culture environment. Differences in deafferentation, cellular maturation, trophic dependence and ongoing naturally occurring cell death may produce changes in the neuronal population that are transparent to the experimenter but that could affect experimental results significantly. In this study, we examined the distribution and prevalence of cell death among neurons in each cortical layer in organotypic slices. In addition, we assessed the ability of several neurotrophic factors to ameliorate neuronal death in each cortical layer. Within the first 24 hr in culture, there was striking laminar variation in the extent of neuronal death in culture, which could not be accounted for by the pattern of programmed cell death in vivo. In addition, neurons in the six layers of the neocortex differed in the degree to which they could be rescued by neurotrophic factors. These data suggest that differential neuronal death and rescue are important considerations in studies utilizing organotypic slices and may represent particularly confounding variables in studies of effects of trophic factors in such preparations. J. Neurosci. Res. 65:455–462, 2001. © 2001 Wiley‐Liss, Inc.
Bayesian hazard analysis of heavy precipitation in eastern Spain
Authors: Egozcue J.J. , Ramis C. 
Published: August 2002

AbstractThe hazard due to heavy daily rainfall in the Valencia region (eastern Iberian Peninsula) is analysed by using 30‐year records at 72 rain gauge stations. The proposed method is a Bayesian version of the commonly used point over threshold or exceedance methods. For each site, the occurrence of events in time are assumed to be Poisson distributed and the excesses over a selected high threshold are assumed to follow some generalized Pareto distribution. A large uncertainty about the type of distribution for the excesses is observed for each station and the preferred distribution changes from station to station. The large uncertainty in estimated occurrence probabilities or return periods suggests the use of Bayesian predictive occurrence probabilities as the main parameters describing the hazard. Two stations are selected for a detailed analysis. The whole database has been used to obtain predictive exceedance probability spatial distributions for thresholds of 150, 300 and 500 mm of daily precipitation. These maps confirm the most hazardous sites are placed at the northeast of the main mountain range of the region, where it is speculated that deep convection develops when humid northeasterly flows cross the coastal range. Copyright © 2001 Royal Meteorological Society
Transient climate simulation forced by natural and anthropogenic climate forcings
Authors: Bertrand Cédric , Ypersele Jean‐Pascal van 
Published: August 2002

AbstractNumerical experiments have been carried out with a two‐dimensional sector‐averaged global climate model coupled to a diffusive ocean in order to assess the potential impact of four hypothesized mechanisms of decadal to century‐scale climate variability, both natural and anthropogenically induced: (1) solar variability; (2) variability in volcanic aerosol loading of the atmosphere; (3) anthropogenic increase of sulphate aerosols' concentration; (4) anthropogenic increase of greenhouse gas concentrations.Our results suggest that neither the individual responses nor the combined natural or anthropogenic forcings allow one to reproduce all of the recorded major temperature fluctuations since the latter half of the 19th century. They show that these temperature variations are the result of both naturally driven climate fluctuations and the effects of industrialization.By contrast, the dominant cause of decade‐to‐century‐scale variability of the 21st century is likely to be changes in atmospheric trace‐gas concentrations. Indeed, when the solar, volcanic, and tropospheric aerosols forcings used in our experiments are extended into the future, they are unable to counter the expected greenhouse warming. Copyright © 2002 Royal Meteorological Society.
Time‐resolved study of the photochemical reaction of 4‐dimethylaminobenzonitrile with carbon tetrachloride
Authors: Ma C. , Kwok W. M. , Matousek P. , Parker A. W. , Phillips D. , Toner W. T. , Towrie M. 
Published: August 2002

AbstractThe mechanism of 4‐dimethylaminobenzonitrile (DMABN) fluorescence quenching by carbon tetrachloride was studied using time‐resolved fluorescence, absorption and Raman techniques. Picosecond and nanosecond time‐resolved Raman spectra of DMABN and DMABN‐d6 were obtained in resonance with different electronic states to identify intermediates, their structure and time‐dependent dynamic changes. The quenching is attributed to intermolecular electron transfer between B‐state DMABN and carbon tetrachloride with a time constant of ∼500 fs leading to the formation of the DMABN radical cation as the initial intermediate followed by a ∼13 ps process yielding a DMABN Cl adduct as product with a lifetime longer than 50 ns. It is likely that the chlorine atom is located at the amino para‐ring position of the highly reactive DMABN radical cation. It is suggested that this reaction mechanism is general for other donor–aromatic–acceptor type DMABN derivatives. Copyright © 2001 John Wiley & Sons, Ltd.
Size dependence of the Raman spectra in an amorphous–nanocrystalline mixed phase: the glacial state of triphenyl phosphite
Authors: Hédoux Alain , Guinet Yannick , Descamps Marc 
Published: August 2002

AbstractRaman scattering investigations on triphenyl phosphite, performed in both the low‐ and high‐wavenumber ranges, provide a detailed description of the glacial state. The latter can be described as a two‐phase (amorphous–nanocrystalline) system if it is prepared by isothermal aging in the 210–222 K temperature range. From two different procedures the nanocrystalline volume fraction can be determined in glacial states prepared in the above temperature range. The Raman spectra in the range 840–1640 cm−1 reveals that Ta = 224 K is a critical temperature from which the supercooled liquid isothermally transforms into a microstructure rather than nanocrystallized domains. In this case the volume of the non‐transformed supercooled liquid remaining in the intergranular space was estimated with respect to the volume of crystallized matter. Copyright © 2001 John Wiley & Sons, Ltd.