bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aminooxyacetic Acid Results in Excitotoxin Lesions by a Novel Indirect Mechanism
Authors: Beal M. Flint , Swartz Kenton J. , Hyman Bradley T. , Storey Elsdon , Finn Stephen F. , Koroshetz Walter 
Published: October 2006

AbstractAminooxyacetic acid (AOAA) is an inhibitor of several pyridoxal phosphate‐dependent enzymes in the brain. In the present experiments intrastriatal injections of AOAA produced dose‐dependent excitotoxic lesions. The lesions were dependent on a pyridoxal phosphate mechanism because pyridoxine blocked them. The lesions were blocked by the noncompetitive N‐methyl‐D‐aspartate (NMDA) antagonist MK‐801 and by coinjection of kynurenate, a result indicating an NMDA receptor‐mediated excitotoxic process. Electrophysiologic studies showed that AOAA does not directly activate ugand‐gated ion channels in cultured cortical or striatal neurons. Pentobarbital anesthesia attenuated the lesions. AOAA injections resulted in significant increases in lactate content and depletions of ATP levels. AOAA striatal lesions closely resemble Huntington's disease both neurochemically and histologically because they show striking sparing of NADPH‐diaphorase and large neurons within the lesioned area. AOAA produces excitotoxic lesions by a novel indirect mechanism, which appears to be due to impairment of intracellular energy metabolism, secondary to its ability to block the mitochondrial malate‐aspartate shunt. These results raise the possibility that a regional impairment of intracellular energy metabolism may secondarily result in excitotoxic neuronal death in chronic neurodegenerative illnesses, such as Huntington's disease.
Partial Purification of a Novel N‐Ethylmaleimide‐Activated Translational Inhibitor from Adult Rat Brain
Authors: Alcázar Alberto , Martín M. Elena , García Ana , Fando Juan L. , Salinas Matilde 
Published: October 2006

AbstractA translational inhibitor that is activated by N‐ethylmaleimide treatment can be found in the postmicrosomal fraction prepared from the brain of adult rats, but it is almost undetectable in the same fraction prepared from suckling animals. The inhibitor is thermolabile and remains in the supernatant fraction after precipitation at pH 5. During the purification procedure, the inhibitor in its unactivated state binds to the anion exchanger (diethylaminoethyl‐cellulose) but not to the cation exchanger (phosphocellulose). Treatment with N‐ethylmaleimide increases inhibitor affinity for the cation exchanger, and this chromatographic step purifies the inhibitor by 143‐fold. Both the thermolabile nature and the behavior of the inhibitory activity during the different steps of the purification procedure suggest that this activity is most probably due to a protein. Although the addition of initiation factor 2 reverses the inhibition of protein synthesis in the presence of ATP and Mg2+, the inhibitor does not phosphorylate any of the initiation factor subunits “in vitro,” which indicates that it does not contain any intrinsic protein kinase activity. However, its presence in both a crude and a purified preparation of a kinase of the α subunit of a brain eukaryotic initiation factor increases the phosphorylation of the α subunit of the initiation factor. The mechanism of action of this inhibitor is discussed.
Noradrenaline‐Induced Prostaglandin Production by Sympathetic Postganglionic Neurons Is Mediated by α2‐Adrenergic Receptors
Authors: Gonzales Ralph , Sherbourne Caroline D. , Goldyne Marc E. , Levine Jon D. 
Published: October 2006

AbstractIn this study we have demonstrated that noradrenaline increases the levels of prostaglandin E2 and prostaglandin I2 (detected as the stable metabolite 6‐keto‐prostaglandin F1α) synthesized by homogenates of superior cervical ganglia from the adult rat. This noradrenaline‐induced prostaglandin production was further characterized: (a) Selective destruction of adrenergic sympathetic postganglionic neurons in the ganglia using 6‐hydroxydopamine abolished both basal and stimulated prostaglandin production, (b) Elimination of preganglionic cholinergic sympathetic nerve terminals in the ganglia had no effect, (c) Mepacrine (a phospholipase inhibitor) and indomethacin (a cyclooxygenase inhibitor) attenuated both basal and stimulated prostaglandin production. (d) Yohimbine, but not prazosin, suppressed the noradrenaline dose‐response curve for prostaglandin production. The results of these experiments show that, in vitro, noradrenaline stimulates de novo synthesis of prostaglandin E2 and prostaglandin I2 by sympathetic postganglionic neurons. This stimulation by noradrenaline appears to result from action at an α2‐adrenergic receptor.
Activation of High‐Affinity Uptake of Glutamate by Phorbol Esters in Primary Glial Cell Cultures
Authors: Casado Mariano , Zafra Francisco , Aragón Carmen , Giménez Cecilio 
Published: October 2006

AbstractThe effects of 12‐O‐tetradecanoylphorbol 13‐acetate (TPA), a potent activator of protein kinase C, on high‐affinity Na+‐dependent glutamate transport were investigated in primary cultures of neurons and glial cells from rat brain cortex. Incubation of glial cells with TPA led to concentration‐ and time‐dependent increases in the glutamate transport that could be completely suppressed by the addition of the protein kinase C (PKC) inhibitor 1‐(5‐isoquinolinylsulfonyl)‐2‐methylpiperazine. The TPA effects could be mimicked by oleoylacetylglycerol and by the diacylglycerol kinase inhibitor R59022. The effects of TPA were potentiated by the Ca2+ ionophore A23187. Under the chosen experimental conditions TPA had no effect on glutamate transport in neurons. We conclude that PKC activates the sodium‐dependent high‐affinity glutamate transport in glial cells and that it has dissimilar effects on neurons and glial cells.
Mode of Action of Palytoxin on the Release of Acetylcholine from Rat Cerebrocortical Synaptosomes
Authors: Satoh Eiki , Nakazato Yoshikazu 
Published: October 2006

AbstractPalytoxin (PTX; KT−4‐10−6 M) caused a dose‐dependent increase in the release of [3H] acetylcholine ([3H] ACh), cytosolic free Ca2+ concentration ([Ca2+]i), and uptake of 22Na+ and decrease in membrane potential in rat cerebrocortical synaptosomes. The dose‐response curves for the PTX‐induced increases in [3H] ACh release and in [Ca2+]iwere depressed by removing extracellular Ca2+ or by decreasing extracellular Na+ concentrations. The release of [3H] ACh induced by concentrations of PTX < 10−10M was more dependent on the simultaneous presence of both Ca2+ and Na+than the release induced by higher concentrations of PTX. The PTX‐induced increase both in [3H] ACh release and in {Ca2+]i was almost completely abolished by the combination of Ca2+ deprivation and Na+ concentration reduction. All responses to PTX were highly resistant to 10−6M tetrodotoxin. These results suggest that low concentrations of PTX cause depolarization as a result of an increase in Na+ permeability through tetrodotoxin‐insensitive channels. This, in turn, increases Ca2+ influx and leads to an increase in the release of ACh. It appears that at high concentrations PTX increases the release of [3H] ACh by directly increasing the influx of Ca2+ into synaptosomes and by releasing Ca2+ from intracellular storage sites via an Na+‐Ca2+ exchange mechanism.
Regulation of Prostaglandin E2 Receptor Binding Activity in Porcine Temporal Cortex by Protein Phosphorylation
Authors: Morii Hiroshi , Tanemura Mihoko , Watanabe Yasuyoshi 
Published: October 2006

AbstractRegulation of prostaglandin (PG) E2 receptors was investigated in a 3‐[(3‐cholamidopropyl) dimethylammonio]‐ 1‐propanesulfonate‐solubilized fraction from the synaptic membrane of porcine temporal cortex. The fraction was preincubated with exogenous protein kinases, and then the binding of PGE2 was measured. PGE2 binding was increased approximately twofold by pretreatment with the catalytic subunit of cyclic AMP‐dependent protein kinase (A kinase) or calmodulin‐dependent protein kinase II but not by that with protein kinase C. The increase was dependent on the ATP concentration, with ED50 values being close to the ATmvalues of these protein kinases. Protein kinase inhibitors specific for A kinase and for calmodulin‐dependent protein kinase II abolished the effect in a dose‐dependent manner, with IC50 values being similar to those reported. Further study using the catalytic subunit of A kinase revealed that the maximal binding capacity apparently increased without affecting the affinity and the rate constants for association and dissociation. On the other hand, acid phosphatase treatment reduced the binding activity to the level of nonspecific binding. In addition, treatment by A kinase did not affect the binding of guanosine 5′‐(3‐thiotriphosphate) by the GTP‐binding proteins and the activation of adenylate cyclase mediated by stimulatory guanine nucleotide‐binding regulatory protein, and therefore the phosphorylation is believed to occur on the receptor protein. The results suggest that the PGE2 receptor can take active phosphorylated and inactive dephosphorylated forms, of which only the phosphorylated one can bind PGE2.
Agonist‐Dependent Internalization of γ‐Aminobutyric AcidA/Benzodiazepine Receptors in Chick Cortical Neurons
Authors: Tehrani Mohammad H. Jalilian , Barnes Eugene M. 
Published: October 2006

AbstractAn impermeant benzodiazepine receptor ligand was prepared by derivatization of the aminobenzodiazepine 1012‐S with 4‐sulfophenylisothiocyanate. The resulting N‐sulfophenyl)‐thiocarbamoyl derivative of 1012‐S (SPTC‐1012S) was purified by reverse‐phase HPLC, and the predicted structure was verified by mass spectrometry. The apparent affinity of SPTC‐1012S (IC50= 9.8 ± 2.9 nM) for displacement of [3H] flunitrazepam from intact chick cortical neurons was similar to that of 1012‐S (IC50= 4.0 ±0.3 nM). However, at concentrations from 0.1 to 10 μM, 1012‐S was consistently more efficacious than SPTC‐1012S, a finding indicating that 6‐8% of the benzodiazepine receptor pool was not accessible to the impermeant compound. This inaccessible pool was eliminated by permeabilization of the cells with saponin or Triton ±‐100, a result suggesting that ∼7% of neuronal benzodiazepine receptors are intracellular. Acute treatment (1–4 h at 37°C) of neurons with 100μMγ‐aminobutyric acid (GABA) or 100 nM clonazepam had little effect on the level of [3H] flunitrazepam binding but increased the proportion of intracellular receptors by 61 and 74%, respectively, compared with untreated controls. Similar treatment with 1 mM GABA increased the level of intracellular sites by 154–176%. The effect of GABA on receptor internalization was blocked by cotreatment with the GABAA receptor antagonist R 5135. The results suggest that SPTC‐1012S can be used as a probe to study the internalization of the GABAA/benzodiazepine receptor complex under normal conditions or following acute or chronic treatment with agonists.
Selective and Nonselective Effects of 1‐Methyl‐4‐ Phenylpyridinium on Oxygen Consumption in Rat Striatal and Hippocampal Slices
Authors: Martin Frederick R. , Sanchez‐Ramos Juan , Rosenthal Myron 
Published: October 2006

AbstractInsights into the etiology and pathophysiology of Parkinson's disease may derive from elucidation of the neurotoxic mechanisms of 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine (MPTP) and its active metabolite, I‐methyl‐4‐phenylpyridinium (MPP+). In previous studies, MPP+ provoked oxidation of cytochrome b and K+ leakage into the extracellular space of rat striatal slices. Magnitudes of these time‐dependent responses were far greater than expected had the MPP+ effects been limited to dopaminergic terminals. To determine whether cytochromes become oxidized from K+‐induced increases in ion transport activity or from electron transport inhibition at complex I, oxygen consumption was measured because this should be increased by the former and decreased by the latter mechanism. Low MPP+ concentrations (1 μM) decreased O2 consumption (∼40% in 3 h) in striatal slices. This decrease was diminished by mazindol and did not occur in hippocampal slices. High toxin concentrations (100 μM) inhibited oxygen consumption to a greater extent (∼60%) in striatal slices; this inhibition was still greater in hippocampal slices. These results support the hypothesis that acute effects of low (“selective”) MPP+ concentrations require the presence of dopaminergic terminals to trigger a sequence of destructive metabolic events but that the metabolic consequences of MPP+ spread to neighboring cells. In contrast, high MPP+ concentrations nonselectively inhibit metabolic and ion transport activity without requiring the presence of dopaminergic terminals. These results also suggest that physiological effects of “selective” MPP+ concentrations extend to nondopaminergic cells.
Mono‐ADP‐Ribosylation in Brain: Purification and Characterization of ADP‐Ribosyltransferases Affecting Actin from Rat Brain
Authors: Matsuyama Satoshi , Tsuyama Shingo 
Published: October 2006

AbstractFour ADP‐ribosyltransferases that acted on non‐muscle actin were purified more than 3,000‐fold from rat brain extract. The molecular weights of these brain ADP‐ribosyltransferases were 66,000 as estimated by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis and gel filtration on TSK gel G3000SW. The Km values for NAD were approximately 20 μM. These enzymes were not inhibited by thymidine or nicotinamide, but were inhibited by ADP and ADP‐ribose. Two soluble ADP‐ribosylation factors purified from rat brain had different effects on the four ADP‐ribosyltransferases during the ADP‐ribosylation of non‐muscle actin. These ADP‐ribosyltransferases modified not only actin but also the stimulatory guanine nucleotide‐binding protein of adenylate cyclase, Gs, and another guanine nucleotide‐binding protein in brain, Go. These findings suggest that the four brain ADP‐ribosyltransferases are concerned with nerve functions in the central nervous system.
Glucocorticoids Inhibit Glucose Transport and Glutamate Uptake in Hippocampal Astrocytes: Implications for Glucocorticoid Neurotoxicity
Authors: Virgin Charles E. , Ha Taryn P.‐T. , Packan Desta R. , Tombaugh Geoffrey C. , Yang Susan H. , Homer Heidi C. , Sapolsky Robert M. 
Published: October 2006

AbstractGlucocorticoids (GCs), the adrenal steroid hormones secreted during stress, can damage the hippocampus and impair its capacity to survive coincident neurological insults. This GC endangerment of the hippocampus is energetic in nature, as it can be prevented when neurons are supplemented with additional energy substrates. This energetic endangerment might arise from the ability of GCs to inhibit glucose transport into both hippocampal neurons and astrocytes. The present study explores the GC inhibition in astrocytes. (1) GCs inhibited glucose transport approximately 15–30% in both primary and secondary hippocampal astrocyte cultures. (2) The parameters of inhibition agreed with the mechanisms of GC inhibition of glucose transport in peripheral tissues: A minimum of 4 h of GC exposure were required, and the effect was steroid specific (i.e., it was not triggered by estrogen, progesterone, or testosterone) and tissue specific (i.e., it was not triggered by GCs in cerebellar or cortical cultures). (3) Similar GC treatment caused a decrease in astrocyte survival during hypoglycemia and a decrease in the affinity of glutamate uptake. This latter observation suggests that GCs might impair the ability of astrocytes to aid neurons during times of neurologic crisis (i.e., by impairing their ability to remove damaging glutamate from the synapse).
Chronic Ethanol Treatment Alters Brain Levels of γ‐Aminobutyric AcidA Receptor Subunit mRNAs: Relationship to Genetic Differences in Ethanol Withdrawal Seizure Severity
Authors: Buck Kari J. , Hahner Lisa , Sikela James , Harris R. Adron 
Published: October 2006

AbstractChronic ethanol treatment is known to alter the function of the γ‐aminobutyric acidA (GABAA) benzodiazepine receptor complex. To determine if genetic differences in development of ethanol dependence are related to expression of GABAA receptor subunits, we measured whole brain levels of mRNA for the α1α3, α6, γ2s, γ2t, and γ3 receptor subunits in withdrawal seizure‐prone and ‐resistant (WSP and WSR, respectively) mice fed an ethanol‐containing liquid diet or a control diet Brain poly(A)+ RNA was converted to cDNA and amplified by the polymerase chain reaction using primers conserved among GABAA receptor subunits. Quantification was carried out by densitometric analysis of Southern blots generated using subunit‐specific probes. Chronic ethanol treatment decreased the content of α1, mRNA in WSP but not WSR mice and decreased the content of α6 mRNA in WSR but not WSP mice. The content of γ3 mRNA was increased by chronic ethanol in both lines. In untreated mice, the WSP line had lower levels of α3 and α6 mRNA than the WSR line. Thus, a decrease in the content of α1 mRNA is most clearly linked with development of withdrawal signs, although the amounts of α6 and α3 may also be important in the genetic differences between WSP and WSR mice. In contrast, levels of mRNA for γ2S and γ2L subunits do not appear to be altered in ethanol dependence.
Identification of B2 Bradykinin Binding Sites on Cultured Cortical Astrocytes
Authors: Cholewinski A. J. , Stevens G. , McDermott A. M. , Wilkin G. P. 
Published: October 2006

AbstractBradykinin was found to bind to specific high‐affinity sites in cultured cortical astrocytes from rat brain, and this binding appeared to be specific for the B2 bradykinin receptor subtype. Nonlinear regression analysis of saturation experiments using a computer programme revealed a single KD of 16.6 ± 2.6 nM and a Bmax of 352.2 ±30.7 fmol/mg of protein. These results indicate that astrocytes possess bradykinin receptors and that these are predominantly of the B2 subtype.
Involvement of Growth‐Associated Protein‐43 with Irreversible Neurite Outgrowth by Dibutyryl Cyclic AMP and Phorbol Ester in NG108–15 Cells
Authors: Kumagai Chihiro , Tohda Michihisa , Isobe Masaharu , Nomura Yasuyuki 
Published: October 2006

AbstractSimultaneous treatment with 12‐O‐tetradecanoylphorbol 13‐acetate (TPA) and dibutyryl cyclic AMP (diBu‐cAMP) for 72 h induced neurites in NG108–15 cells significantly longer than treatment with each alone. Treatment for 72 h with both drugs induced irreversible neurite extension and a decline in protein kinase C activity, although neurites extended by diBu‐cAMP alone disappeared after the withdrawal of the drug. The expression of growth‐associated protein‐43 (GAP‐43) mRNA was also observed by a combined application of TPA and diBu‐cAMP. The increased level of GAP‐43 mRNA induced by treatment with both drugs for 72 h was maintained at least 24 h after withdrawal of the drugs. In cells transfected with GAP‐43 cDNA, neurites induced by treatment with diBu‐cAMP alone for 72 h were maintained at least 48 h after removal of the drugs. These results suggest that GAP‐43 could be involved in the maintenance of elongated neurites and that a decline in protein kinase C activity may be involved in the accumulation of GAP‐43.
Mapping of Histamine H1 Receptors in the Human Brain Using [11C]Pyrilamine and Positron Emission Tomography
Authors: Yanai Kazuhiko , Watanabe Takehiko , Yokoyama Hiroyuki , Hatazawa Jun , Iwata Ren , Ishiwata Kiichi , Meguro Kenichi , Itoh Masatoshi , Takahashi Toshihiro , Ido Tatsuo , Matsuzawa Taiju 
Published: October 2006

AbstractWe have studied the characteristics of carbon‐11 labeled pyrilamine as a radioligand for investigating histamine H1 receptors in human brain with positron emission tomography (PET). [11QPyrilamine is distributed evenly in proportion to cerebral blood flow at initial PET images. Later (after 45–60 min), 11C radioactivity was observed at high concentrations in the frontal and temporal cortex, hippocampus, and thalamus, and at low concentrations in the cerebellum and pons. The regional distribution of the carbon‐11 labeled compound in the brain corresponded well with that of the histamine H1 receptors determined in vitro in autopsied materials. In six controls, the frontal and temporal cortices/cerebellum ratio increased during the first 60 min to reach a value of 1.22 ± 0.071. Intravenous administration of d‐chlorpheniramine (5 mg) completely abolished the specific binding in vivo in the frontal cortex and temporal cortex (cortex/cerebellum ratio, 0.955 ±0.015). The availability of this method for measuring histamine H1 receptors in vivo in humans will facilitate studies on neurological and psychiatric disorders in which histamine H1 receptors are thought to be abnormal.
Temporal Profiles of Nerve Growth Factor β‐Subunit Level in Rat Brain Regions After Transient Ischemia
Authors: Shozuhara Hidetaka , Onodera Hiroshi , Katoh‐Semba Rituko , Kato Kanefusa , Yamasaki Yasundo , Kogure Kyuya 
Published: October 2006

AbstractTo determine the role of nerve growth factor (NGF) in ischemic brain damage, we measured the temporal and regional changes in the level of NGF in the hippo‐campal subfields, the cerebral cortex, the striatum, and the septum at 1, 2, 7, and 30 days after transient forebrain ischemia using a highly sensitive sandwich‐type enzyme im‐munoassay system for the β‐subunit of mouse 7S NGF (β‐NGF). We also analyzed glial fibrillary acidic protein immunoreactivity in the hippocampus to ascertain the contribution of reactive astrocytes to NGF production after an ischemic insult. In the CA1 subfield of the hippocampus, the level of β‐NGF decreased slightly 2 days after ischemia (not significant), at which time CA1 pyramidal cell loss began to occur, and increased by 40% 30 days after ischemia (p < 0.05). A marked increase in glial fibrillary acidic pro‐tein‐positive astrocytes in the CA1 subfield 2–30 days after ischemia suggests that the reactive astrocytes participated in a gradual increase in the level of β‐NGF after recirculation. The level of β‐NGF in the dentate gyrus decreased transiently 2 days (p < 0.05) and 7 days (p < 0.01) after ischemia, followed by recovery to the level of control animals 30 days after ischemia. The level of β‐NGF in the septum gradually decreased 7 days (−27%, p < 0.05) and 30 days (−43%, p < 0.01) after ischemia. The levels of β‐NGF in the cerebral cortex and striatum remained unaltered throughout the observation period. These results suggest that the alteration of NGF content occurs not only in the CA1 subfield, where pyramidal cells are depleted, but also in areas with minimal histological damage. Septal decrease in NGF may reflect the reduction of retrograde NGF transport from hippocampus to septal cholinergic neurons.
A Cyclic AMP Mechanism Mediates the Serotonin‐Induced Increase in Glutamic Acid Decarboxylase Activity in the Preoptic Area and Hypothalamus
Authors: Munaro N. I. , Taleisnik S. 
Published: October 2006

AbstractPrevious studies have shown that the injection of 5‐hydroxytryptamine (5‐HT) into the third ventricle of rats on the afternoon of proestrus increases glutamic acid decarboxylase (GAD) activity in the preoptic area and the hypothalamus. In the present report we examine the adenylate cyclase‐cyclic AMP (cAMP) system as mediator of that effect. The increase in GAD activity induced by intraventricu‐lar injection of 5‐HT was completely blocked by injecting an antiserum against cAMP into the third ventricle 30 min earlier, whereas an injection of serum from normal rabbits was ineffective. On the contrary, activation of adenylate cy‐clase activity by intraventricular injection of forskolin increased GAD activity, an effect that was also blocked by anti‐cAMP serum. Anti‐cAMP serum also lowered GAD activity in the preoptic area and hypothalamus when injected on the morning of proestrus but not when injected in the afternoon, when the values of GAD activity were already low. The results suggest that a cAMP mechanism may be involved in the changes in preoptic‐area and hypotha‐lamic GAD activity such as the rise in enzyme activity induced by intraventricular injection of 5‐HT.