bluuebunny/crossref_metadata_2025 huggingface dataset:
ENZYMES CATALYZING THE DE NOVO SYNTHESIS OF METHYL GROUPS IN THE BRAIN AND OTHER TISSUES OF THE RAT
Authors: Ordóñez L. A. , Wurtman R. J.
Published: October 2006

—Rat brain contains all three of the enzymes required for de novo synthesis of the methyl group of methionine (serine transhydroxymethylase, methylene reductase, and [B12]transmethylase) in activities comparable to those found in liver and kidney. The activities of methylene reductase in female kidney, and of [B12]transmethylase in female brain and kidney, are higher than in the corresponding male tissues. Liver and kidney extracts contain an inhibitor of methylene reductase not present in brain extracts. This inhibitor differs from S‐adenosylmethionine (SAM), which also inhibits methylene reductase in both liver and brain homogenates. The administration of l‐DOPA to rats, which has been previously shown to deplete brain S‐adenosylmethionine, also reduces the activity of brain [B12]transmethylase if assayed without added SAM. Since SAM is required for activity of this enzyme, its decreased activity probably results from the decline in brain SAM concentration. De now synthesis of methyl groups could be a mechanism by which the brain maintains its level of methionine in the face of increased methyl group utilization after administration of l‐DOPA.
GANGLIOSIDES OF HUMAN MYELIN: SIALOSYLGALACTOSYLCERAMIDE (G7) AS A MAJOR COMPONENT
Authors: Ledeen R. W. , Yu R. K. , Eng L. F.
Published: October 2006

Abstract— Gangliosides were isolated from purified human myelin in a yield of 62 μg of lipid‐bound sialic acid per 100 mg of dry myelin. Sialosylgalactosyl ceramide (G7) was found to be a major component of the ganglioside fraction, amounting to 15 per cent of the total sialic acid. It accounted for 10 per cent of lipid‐bound sialic acid in adult human white matter, making it the third most abundant ganglioside on a molar basis. These results were obtained with an improved method for isolating total gangliosides in high yield, by employing DEAE‐Sephadex column chromatography. Myelin from other mammalian species had considerably less G7, and there were also indications of maturational changes. Both 2‐hydroxy and unsubstituted fatty acids were components of the ceramide unit, in a ratio of 3:2, respectively. The overall fatty acid pattern was very similar to that for myelin cerebroside and sulphatide. Long‐chain bases included only C18 species, with sphingosine predominating (>90 per cent). These observations suggest a metabolic relationship between G7 and either cerebroside or sulphatide.
KINETICS OF THE INCORPORATION OF SOME TRITIATED NUCLEIC ACID PRECURSORS AND [3H]LYSINE INTO MOUSE BRAIN CELLS FOLLOWING INTRAPERITONEAL INJECTION
Authors: Pakkenberg H. , Fog R.
Published: October 2006

Abstract— Intraperitoneal injection into white mice of the same amount of radioactivity (0.5 mCi) of [3H]uridine and [3H]lysine demonstrated by autoradiography that there was a much greater labelling of nerve cells from lysine than from uridine. For uridine, the choroid plexus cell nuclei gave maximal labelling within 1 h, with a decrease after 6 h. The plexus nuclei of lysine‐injected animals gave almost the same amount of labelling during the experimental period of 48 h. In nerve cells, labelling from uridine increased in the nuclei up to 18 h after injection and there was an almost parallel increase in the labelling in the cytoplasm and neuropil. These results are compared with earlier reports on the results from intravenous injection of uridine. In lysine‐injected animals the nerve cell nuclei and cytoplasm showed a fairly constant amount of label over 48 h, but the neuropil counts increased steeply. The activity of the blood was determined by scintillation counting during the 48‐h period, and, as with uridine injection, was found to be almost constant over this period. A small series of animals was injected with 0.5 mCi of [3H]uracil, [3H]guanine, [3H]guanosine or [3H]cytidine for comparison. The autoradiograms from animals injected with these bases showed very slight labelling; that from guanosine was heavy in plexus nuclei, slight in nerve cells, and from cytidine it was heavy in plexus cells and moderate in nerve cells.
THE STRUCTURE OF BRAIN POLYISOPRENOLS1
Authors: Breckenridge W. Carl , Wolfe L. S. , Ng Ying Kin N. M. K.
Published: October 2006

Abstract— Long‐chain polyisoprenols were isolated from brain in yields of 10‐15 mg/kg tissue wet weight. On thin‐layer chromatography, migrations were identical for brain polyisoprenols and pig liver dolichol which had been isolated as reference material. The IR, 1H NMR and 13C (FT) NMR spectra of calf brain polyisoprenols were consistent with a molecular structure which had a saturated isoprenol unit followed by approximately 19 unsaturated isoprene units. About 3‐4 isoprene units possessed trans double bonds. Using reversed phase thin‐layer chromatography and pig liver dolichol as a reference, it was estimated that calf brain polyisoprenols had major structures of C95, C100 and C105 while rat brain polyisoprenols contained C90 and C95 as the major components. All data indicated that the brain polyisoprenols were very similar, chemically, to pig liver dolichols except for minor differences in molecular weight.
METABOLISME DU CALCIUM ET LIBERATION DE L'ACETYLCHOLINE DANS L'ORGANE ELECTRIQUE DE LA TORPILLE
Authors: Babel‐Guérin Eliane
Published: October 2006

Résumé—

Le métabolisme du'calcium a étéétudié dans l'organe électrique de la Torpille, au repos et en activité, in vivo et in vitro, en mesurant le calcium total et en utilisant du 45Ca. Lorsque le tissu est mis en présence de fortes concentrations de calcium, un échange complet s'effectue entre le calcium cellulaire et celui du milieu d'incubation. En présence de faibles concentrations, le tissu retient son calcium qui, dans ce cas, séchange mal avec l'extérieur. La stimulation cause une augmentation nette du calcium cellulaire et accélère son échange avec le milieu extérieur. Cette entrée de calcium concerne principalement les terminaisons nerveuses présynaptiques car on l'observe aussi lorsque la transmission est bloquée par le curare qui agit au niveaja des électroplaques. Il semble que le calcium influence la répartition intracellulaire du transmetteur. En effet, l'entrée présynaptique de calcium s'accompagne d'une diminution de l'ACh ‘liée’ (vésiculaire). Lorsque le tissu est incubé dans une solution exempte de calcium, surtout en présence d'EDTA, la réponse électrophysiologique disparaît; le taux d'ACh ‘libre’ (disponible) diminue alors, mais son ‘turnover’ augmente. Le calcium extracellulaire est donc nécessaire au maintien du compartiment d'ACh immédiatement disponible.
THE INCORPORATION OF GLUCOSE INTO BRAIN GLYCOGEN AND THE ACTIVITIES OF CEREBRAL GLYCOGEN PHOSPHORYLASE AND SYNTHETASE: SOME EFFECTS OF AMPHETAMINE
Authors: Nahorski S. R. , Rogers K. J.
Published: October 2006

Abstract— The effects of amphetamine sulphate (5 mg/kg intraperitoneally) on the incorporation of radioactive carbon from [U‐14C]glucose into the glycogen of mouse cerebral cortex, midbrain and hind‐brain have been investigated. In all brain regions studied amphetamine induced a rapid decrease in glycogen followed by a slower return to control values. No significant alterations were observed in the steady state concentration of cerebral glucose. The initial fall in glycogen was associated with a fall in its specific radioactivity relative to that of cerebral glucose, whereas the resynthesis of the polysaccharide was associated with a marked increase in the relative specific radioactivity of glycogen. Other experiments demonstrated that amphetamine initially stimulates the breakdown of prelabelled glycogen and that the resulting molecule has fewer 1,4 linked glucose side chains.

Studies of the relative forms of the enzymes glycogen phosphorylase and glycogen synthetase suggested that rapid post mortem changes were less likely to occur if cerebral tissue was fixed by means of a freeze‐blowing technique. Amphetamine administration resulted in a rapid though transient elevation of phosphorylase a activity in mouse forebrain. The level of glycogen synthetase I activity was unchanged initially but was markedly elevated during the period when there was a large increase in the rate of incorporation of glucose into glycogen. It is suggested that cerebral glycogen metabolism is controlled, at least in part, by the interconversion of the ‘active’ and ‘inactive’ forms of glycogen phosphorylase and synthetase.
DETERGENT‐LIKE ACTION OF TETRAPHENYLBORATE ON PHOSPHOLIPID LABELLING IN GUINEA PIG CORTEX SUBFRACTIONS1
Authors: Schacht J. , Agranoff B. W.
Published: October 2006

—The addition of 2 × 10−4m sodium tetraphenylborate to particulate preparations of guinea pig cerebral cortex increases labelling of phosphatidic acid from γ‐[32P]‐ATP two‐ to four‐fold. The effect ‘was observed in all subcellular fractions studied (nuclear, synaptosomal, mitochondrial and microsomal) and is not blocked by the addition of atropine. Changes in phospholipid labelling similar to those induced by tetraphenylborate can be demonstrated with sodium dodecyl sulphate or sodium desoxycholate. It is suggested that tetraphenylborate stimulates lipid labelling by a detergent‐like activation of diglyceride kinase.
COPPER DEFICIENCY IN THE DEVELOPING RAT BRAIN: A POSSIBLE MODEL FOR MENKES’ STEELY‐HAIR DISEASE
Authors: Prohaska J. R. , Wells W. W.
Published: October 2006

Abstract— In comparison to controls, copper‐deficient suckling rats showed an appreciable decrease in body growth, a slight decrease in whole brain and cerebellar growth, and a highly significant decrease in myelination based on the activity of cerebellar 2′,3′‐cyclic nucleotide 3′‐phosphohydrolase—a myelin enriched protein. Specific effects of a fivefold reduction in the copper content of brain were seen in a drastic decrease in cerebellar cytochrome c oxidase and smaller but significant drops in cerebellar super‐oxide dismutase and brain norepinephrine concn. These observations are discussed with respect to the neuropathology and biochemistry of Menkes’ steely‐hair disease, a sex‐linked recessive disorder in humans characterized by copper deficiency.
[14C]GLUTAMATE UPTAKE AND COMPARTMENTATION IN GLIA OF RAT DORSAL SENSORY GANGLION
Authors: Roberts P. J. , Keen P.
Published: October 2006

Abstract— The characteristics of the uptake of l‐[U‐14C] glutamate into rat dorsal sensory ganglia were investigated. The uptake was mediated by two distinct kinetic systems, with apparent Km values of the order of 10−3 M (low affinity) and 10−5m (high affinity). The high affinity uptake system was strongly dependent upon temperature and sodium ion concn, and was depressed by a number of metabolic inhibitors. Following uptake, [14C] glutamate was extensively metabolized, primarily to glutamine, although this was not so with cultured ganglia, where in addition to an increased uptake of [14C] glutamate, the specific radioactivity of glutamate was increased and that of glutamine decreased. The labelled substrates [U‐14C]pyruvate and [U‐14C] acetate were used to investigate this phenomenon and the results are discussed in relation to current knowledge of metabolic compartmentation in nervous tissue.
EFFECT OF NEUROTRANSMITTERS ON PHOSPHOLIPID METABOLISM IN RAT CEREBRAL‐CORTEX SLICES—CELLULAR AND SUBCELLULAR DISTRIBUTION1
Authors: Abdel‐Latif A. A. , Yau S.‐J. , Smith J. P.
Published: October 2006

Abstract— Young rat cerebral‐cortex slices were incubated with 32Pi in the absence and presence of ACh plus eserine, norepinephrine, dopamine or serotonin for 1 h. their cellular and subcellular fractions were isolated, and the specific radioactivities of the various phospholipids determined.

In the neuronal‐ and astroglial‐enriched fractions ACh plus eserine increased the 32P‐labelling of phosphatidyl inositol (PhI) phosphatidic acid (PhA) and phosphatidylcholine (PhC) by increments which ranged from 108 per cent for PhI to 30 per cent for PhC and in the presence of norepinephrine or dopamine these increments ranged from 180 per cent for PhI to 29 per cent for PhC.

In the subcellular fractions ACh plus eserine exerted maximal stimulatory effect on the labelling of the synaptosomal phospholipids, which was 88 per cent for PhI and 79 per cent for PhA, followed by those of microsomes, mitochondria and nuclei.

ACh plus eserine exerted no effect on [l4C]glucose incorporation, but inhibited the incorporation of [14C]glycerol into phospholipids by amounts which ranged from 30 per cent for PhI to 3 per cent for PhE.

Although the rate of incorporation of 32Pi into phospholipids of 0.2 mm slices was higher than that of the 0.5 mm slices the stimulatory effect of ACh plus eserine on the 32Pi incorporation into the lipids of the latter was higher.

When neuronal‐ and astroglial enriched fractions were first isolated from the cerebra then incubated with 32Pi or [14C]choline, labelling of phospholipids in the neuronal fraction was higher than that of the astroglial fraction; however, ACh plus eserine had no effect on the incorporation of 32Pi into the lipids of either fraction.

ACh plus eserine stimulated the activity of phosphatidic acid phosphatase in the various subcellular fractions by increments which ranged from 13 per cent in nuclei to 37 per cent in microsomes.

It was concluded that the nonspecific localization of the neurotransmitter effect could be due to the widespread distribution of the enzymes which appear to be responsive to cholinergic and adrenergic neurotransmitters.
MECHANISMS ACTIVATING GLYCOLYSIS IN THE BRAIN IN ARTERIAL HYPOXIA
Authors: Bachelard H. S. , Lewis L. D. , Pontén U. , Siesjö B. K.
Published: October 2006

Abstract— In order to study regulatory steps responsible for the activation of anaerobic glycolysis in the brain during hypoxia, cerebral concentrations of carbohydrate substrates and organic phosphates were measured in rats after reduction of the arterial PO2 to 23‐25 mm Hg for 2, 5 and 15 min. The results demonstrated a progressive accumulation of lactate as well as of pyruvate and malate in the absence of changes in ATP, A DP, AMP, citrate and ammonia. The pattern of substrate changes obtained indicate that hypoxia is accompanied by activation of pyruvate kinase and of hexokinase, but not of phosphofructokinase. There was a progressive fall in intracellular pH and a moderate increase in the calculated cytoplasmic NADH/NAD+ ratio. The changes in pyruvate and in the NADH/NAD+ ratio may be responsible for the observed increase in the malate concentration.
THE EFFECT OF PORTA‐CAVAL ANASTOMOSIS UPON THE ENERGY STATE AND UPON ACID‐BASE PARAMETERS OF THE RAT BRAIN
Authors: Holmin T. , Siesjö B. K.
Published: October 2006

Abstract— In order to evaluate the influence of porta‐caval anastomosis upon the energy state of the brain, lightly anaesthetized rats were studied either 1 or 5 weeks after the shunting procedure and the brains (frontal lobe, cerebellum and brainstem) were analysed for carbohydrate substrates and organic phosphates. The ammonia contents of arterial blood, cerebrospinal fluid (CSF) and tissue increased progressively in the shunted groups and at 5 weeks the increases were three‐ to six‐fold. In all brain structures studied there were decreases in the glucose and in the aspartate contents but regional differences existed for glucose‐6‐phosphate, α‐ketoglutaratc and glutamate. In the brainstem the tissue contents of glucose‐6‐phosphate and α‐ketoglutarate fell while glutamate was unchanged. Calculation of the cytoplasmatic redox state from the lactate dehydrogenase (LDH) and the malate dehydrogenase (MDH) equilibria indicated that the NADH/NAD+ ratio increased in the shunted groups. However, since there was no significant fall in the calculated adenylate energy charge, it is concluded that porta‐caval anastomosis, and the accompanying hyperammonemia, do not disrupt the balance between production and utilization of energy in the brain.
IMMUNOLOGICAL APPROACH TO THE CHARACTERIZATION OF CHOLINERGIC VESICULAR PROTEIN
Authors: Ulmar G. , Whittaker V. P.
Published: October 2006

Abstract— Rabbit antisera have been prepared against whole cholinergic vesicles purified from the electric organ of Torpedo marmorata. The sera contain two major and two minor precipitating systems against membranous proteins, as revealed by Ouchterlony diffusion. No immunoprecipitation could be detected against the soluble vesicle protein constituent ‘vesiculin’. Fractions from cephalopod, amphibian and mammalian neural tissue were shown to exhibit no immunochemical homology with Torpedo cholinergic vesicle proteins.
THE ISOLATION AND PROPERTIES OF LARGE BASIC PEPTIDES FROM BOVINE SPINAL CORD
Authors: Eylar E. H. , Hashim G. A.
Published: October 2006

Abstract— Two basic peptides (B1 and B2) were derived from bovine spinal cord following in situ proteolysis at 37°C for 10–24 h. These peptides do not arise as degradation products from the A1 protein as shown by amino acid composition and end group analysis; rather they appear to originate from some larger basic protein in the spinal cord having similarities to the P2 protein, a basic protein found in peripheral nerve myelin. The peptides were purified following defatting, acid extraction, and ammonium sulphate fractionation, by chromatography on Amberlite IRC‐50 resin using guanidinium chloride. The peptides, found generally in a 4:1 ratio of B1 to B2, appeared homogeneous on gel electrophoresis and immunodiffusion. Approximately 25–60 mg of peptides was obtained per 100 g wet spinal cord.

In contrast to the basic A1 protein from myelin, neither of these peptides nor their pepsin digests were encephalitogenic. They do not cross‐react immunologically with the basic A1 protein, but cross‐react with each other. These peptides further differ from the A1 protein in their tryptic peptide map, size (B1, 63 residues; B2, 54 residues), and composition particularly the high lysine: arginine ratio, and low histidine content. Like the A1 protein, however, they contain a tryptophan residue and a blocked NH2‐terminal amino acid; peptide Bl has COOH‐terminal valine. It was concluded that the basic peptides represent a fragment of a hitherto unidentified protein(s) of the nervous system.
HIGH AFFINITY UPTAKE OF l‐GLUTAMINE IN RAT BRAIN SLICES
Authors: Balcar V. J. , Johnston G. A. R.
Published: October 2006

—l‐Glutamine is taken up into rat brain slices by a specific‘high affinity’uptake system (Km 52 μm) which is not influenced by high concentrations of l‐glutamate and l‐asparagine. The uptake system appears to be associated with cellular structures that do not survive homogenization under conditions which yield synaptosomes. The‘high affinity’uptake of glutamine is dependent on the external sodium ion concentration and can be inhibited by p‐chloromercuriphenylsulphonate, amino‐oxyacetic acid, ouabain, dibenamine and allylglycine. The effects of several inhibitors indicate that l‐asparagine uptake is mediated by a system different from the‘high affinity’system mediating l‐glutamine uptake.
EFFECTS OF CHRONIC PORTO‐CAVAL ANASTOMOSIS ON BRAIN TRYPTOPHAN, TYROSINE AND 5‐HYDROXYTRYPTAMINE
Authors: Curzon G. , Kantamaneni Bharati D. , Fernando J. C. , Woods Margaret S. , Cavanagh J. B.
Published: October 2006

—Three weeks after porto‐caval anastomosis, tryptophan and 5‐hydroxyindolylacetic acid concentrations were‐greatly increased in rat brain regions. 5‐Hydroxytryptamine showed smaller increases. Midbrain tyrosine and muscle tyrosine and tryptophan concentrations were also increased. Striatal dopa‐mine concentration was not significantly changed. Unlike previous results from acute liver failure, brain tryptophan changes in this chronic study did not simply reflect plasma‐free tryptophan changes. Midbrain tryptophan/plasma‐free tryptophan ratio and midbrain tyrosine/plasma tyrosine ratio both rose, suggesting increased effectiveness of uptake of these amino acids from plasma by brain. Corresponding muscle/plasma ratios were unaltered by the porto‐caval anastomosis. Uptake of tryptophan from buffer by cerebral cortex slices was unaffected. Results on control animals illustrate the importance of plasma‐free tryptophan in the normal physiological control of brain tryptophan.
KINETIC PROPERTIES OF PLASMALOGENASE FROM BOVINE BRAIN1
Authors: D'Amato R. A. , Horrocks L. A. , Richardson K. E.
Published: October 2006

Abstract— Plasmalogenase was assayed by measuring the disappearance of the plasmalogen by two‐dimensional thin‐layer chromatography. The enzyme was present in a glycerol‐bicarbonate extract of an acetone‐dried powder from bovine brain. With ethanolamine plasmalogens as the substrate, the Km was 180 μM. Diacyl glycerophosphorylcholines, diacyl glycerophosphorylethanolamines and choline plasmalogens were competitive inhibitors. With choline plasmalogens as the substrate, the Km was 208 μM and competitive inhibition was observed with diacyl glycerophosphorylcholines and ethanolamine plasmalogens. The same enzyme may be responsible for the hydrolysis of the alk‐1‐enyl moiety from both plasmalogens. Plasmalogenase activity was 5.1 μmol/h/g of dog brain, 3.9 μmol/h/g of rat brain and 3.4 μmol/h/g of gerbil brain. A lysophospholipase was also found in the glycerol‐bicarbonate extract from the acetone‐dried powder. The lysophospholipase was more active in hydrolysing acyl groups from 2‐acyl‐sn‐glycero‐3‐phosphorylethanolamines than the plasmalogenase was active in hydrolyzing alk‐1‐enyl groups from 1‐alk‐1′‐enyl‐2‐acyl‐sn‐glycero‐3‐phosphorylethanolamines.
STEARYL COENZYME A DESATURASE ACTIVITIES IN RAT BRAIN MICROSOMES
Authors: Pullarkat R. K. , Reha H.
Published: October 2006

—A quantitative assay for the rat brain microsomal stearyl CoA desaturase is described. The method was used to determine the developmental pattern and regional distribution of the desaturase in rat brain. Even though the specific activity of the enzyme decreased to one‐third from 8 to 60 days of age, the total activity per brain remained the same. The regional distribution of the activity in adult brain was of the order midbrain > medulla oblongata > cerebral hemispheres > cerebellum, with midbrain activity being about twice as that of the cerebellum.
SUBCELLULAR LOCALIZATION AND PROPERTIES OF A CHOLINERGIC RECEPTOR ISOLATED FROM HOUSEFLY HEADS
Authors: Donnellan J. F. , Jewess P. J. , Cattell K. J.
Published: October 2006

—Protein(s) possessing the ligand‐binding properties expected of the insect cholinergic receptor were demonstrated in both aqueous and chloroform‐methanol extracts of an 80,000 g supernatant obtained from frozen housefly heads. There is reasonable correlation in both the properties and concentration of the housefly head cholinergic receptor in these radically different extracts.

Binding constants for decamethonium, acetylcholine, nicotine and atropine have been determined with aqueous housefly head extracts using an ultrafiltration assay. These observations are taken as further evidence that the cholinergic receptor in the insect central nervous system differs in specificity to the more widely studied nicotinic and muscarinic cholinergic receptors from vertebrates.
MYELIN BASIC PROTEIN IN FROZEN AND UNFROZEN BOVINE BRAIN: A STUDY OF AUTOLYTIC CHANGES IN SITU1
Authors: Ansari K. A. , Hendrickson H. , Sinha A. A. , Rand A.
Published: October 2006

Abstract— Frozen and unfrozen bovine brains were used to determine the extent of in situ degradation of myelin basic protein. The following three parameters were investigated. (1) The time interval between death and sampling of the tissue, (2) the effective temperature of the tissue during this interval, and (3) the effect of freezing and thawing on the subsequent autolysis of myelin basic protein. Polyacrylamide gel electrophoresis was carried out on unfrozen white matter solubilized with phenol‐formic acid–water. The resulting electrophoretic pattern showed no qualitative changes in the myelin basic protein after tissue incubation at 4° or 23°C for up to 24 h. When myelin basic protein was extracted, purified and quantitated, there was no apparent decrease within 24 h of incubation at 23°C. However, if the tissue was frozen and thawed prior to incubation, there was a rapid disappearance of myelin basic protein such that only 10% remained after 24 h of incubation. Basic protein extracted from frozen or unfrozen tissue that had undergone autolysis for up to 24 h was found to be encephalitogenic in guinea pigs. Electron microscopy of frozen and thawed material showed separation and fraying of myelin lamellae. It is postulated that the above morphological changes probably render the basic protein readily accessible to proteolytic enzymes.
THE ANTICONVULSANT ACTION OF GABA‐ELEVATING AGENTS: A RE‐EVALUATION
Authors: Wood J. D. , Peesker S. J.
Published: October 2006

Abstract— The GABA‐elevating agents, aminooxyacetic acid, hydrazine, and hydroxylamine, all possessed anticonvulsant properties, although to a widely varying degree. Aminooxyacetic acid was the most efficacious in delaying drug‐induced seizures in mice whereas hydroxylamine brought about only a slight delay in the onset of seizures. The anticonvulsant action was observed against various convulsant agents regardless of whether the convulsant mechanism might involve a deranged GABA metabolism (allylglycine, isonicotinic acid hydrazide, hydrazine), an interference with GABA function (picrotoxin) or some other mechanism (pentylenetetrazol). The anticonvulsant action was not related in a simple manner to either GABA levels or glutamic acid decarboxylase (GAD) activities but the anomalous situation whereby seizures occurred when the GABA content of brain was above normal could be resolved on the basis of an expression which included changes in both GABA levels and GAD activity. The possibility was proposed that the anticonvulsant action of aminooxyacetic acid involved two separate mechanisms.
THE EFFECTS OF HYPERKETONEMIA ON GLYCOLYTIC INTERMEDIATES IN THE DEVELOPING RAT BRAIN
Authors: Ozand P. T. , Stevenson J. H. , Tildon J. T. , Cornrlath M.
Published: October 2006

Abstract— Newborn rats from dams fed on a high fat diet developed increased ketonemia and significant hypertriglyceridemia i.e. “hyperketonemic pups”. This perinatal metabolic stress led to an alteration in the developmental pattern of glycolytic intermediates in their brains.

In control rats, the concentration of glucose 6‐phosphate (G6P) in the brain was high at birth, and gradually decreased to adult values by the third week of life. In contrast, the fructose‐1,6‐diphosphate (FDP) concentration was low at birth and increased thereafter. The lactate concentration was also high at birth but decreased to the adult level by the first day of life. In the brains of control pups, lactate and pyruvate concentrations remained relatively constant during the first 3 weeks of life.

In the brains of hyperketonemic pups, the concentration of G6P was the same as in the control animals at birth but decreased significantly during the first days of life. During early development the concentrations of FDP and pyruvate were significantly lower and the concentration of lactate, higher in the hyperketonemic pups as compared to the control group. The alteration in the concentration of these glycolytic intermediates in the brains of hyperketonemic pups indicated a change in the developmental pattern of glycolysis. The ratio of [lactate]/[pyruvate] also suggested an increased cytoplasmic redox potential in the brains of hyperketonemic pups during the first week of life.
TRANSPORT OF LEUCINE AND SODIUM IN CENTRAL NERVOUS TISSUE: STUDIES ON RETINA IN VITRO1
Authors: Ames A. , Parks J. M. , Nesbett F. B.
Published: October 2006

Abstract—

Unidirectional leucine fluxes were measured in isolated rabbit retina maintained under steady state conditions in medium resembling CSF but with leucine varied from 2 to 20,000 μM. At physiological leucine concentration (11 μM), 1/2 time for outward transport was 88 s and intracellular fluid was cleared of Isotopically labelled leucine at 2.3ml/g dry wt./min; 1/2 time for inward transport was 16 s and interstitial fluid was cleared at 7.5 ml/g dry wt./min. The rate of leucine influx corresponded quite well with its rate of disappearance from the intracellular fluid, over a wide range of concentrations. Exchange diffusion was demonstrated for transport in both directions. There was competition by other amino acids, but no interaction between Na+ and leucine transport could be demonstrated. Kinetic analysis indicated the presence of more than one transport system for leucine. There was an unexpected fall in the efflux coefficient, with reduction in leucine concentration at the lower end of the concentration range, for which an explanation is proposed. Under control conditions, 1/2 time for efflux of intracellular 24Na+ was about 0.9 min. With intracellular Na+ increased 4 fold, l/2 time for efflux was slightly reduced. Problems encountered in measuring fluxes in organized tissue are discussed.
EFFECT OF HYPOCAPNIA, HYPERCAPNIA, AND BLOOD PRESSURE ON NADH FLUORESCENCE, ELECTRICAL ACTIVITY, AND BLOOD FLOW IN NORMAL AND PARTIALLY ISCHEMIC MONKEY CORTEX
Authors: Sundt T. M. , Anderson R. E. , Sharbrough F. W.
Published: October 2006

Abstract—

Nicotinamide adenine dinucleotide fluorescence, cortical reflectance, cortical blood flow, and electroencephalograms were recorded from squirrel monkey brains before, during, and after focal transient cerebral ischemia produced by the temporary clipping of the middle cerebral artery. After release of the occluding clip, the monkeys were followed through an N2‐breathing cycle and then to death from anoxia. The effects of controlled variations in arterial carbon dioxide tensions (Paco2) and mean arterial blood pressures (MABP) were investigated in normal and in ischemic brain. In normal brain, with preserved autoregulation, NADH fluorescence was constant through a wide range in Paco2, MABP, and cortical blood flow. In ischemic brain, NADH levels increased, correlated closely with decreased cortical blood flow and EEG abnormalities, and became dependent on MABP. Artifacts in fluorescent measurements were reduced by: monochromators for excitation, emission, and reflected light; low intensity vertical excitation energy and high sensitivity recording instrumentation; and a small avascular (123 μm) field.
CYSTATHIONINE SYNTHESIS AND DEGRADATION IN BRAIN, LIVER AND KIDNEY OF THE DEVELOPING MONKEY
Authors: Sturman J. A. , Gaull G. E. , Niemann W. H.
Published: October 2006

Abstract— The concentration of cystathionine, along with the specific activities of the enzymes involved in its synthesis and degradation, cystathionine synthasc and cystathionase, respectively, have been measured in brain, liver and kidney of the developing Rhesus monkey from mid‐gestation, through birth and neonatal life, to maturity. The concentration of cystathionine and the specific activity of cystathionine synthase are low in fetal brain. Both parameters increase slowly after birth and reach values found in adult brain at approx 3 months of postnatal age. The activity of cystathionase in brain is low throughout development.

Liver provides a direct contrast in that the concentration of cystathionine and the specific activity of cystathionine synthase are high in the fetus, decreasing rapidly after birth to values found in the adult by 2 weeks of postnatal age. Cystathionase activity is low in fetal liver and increases slowly after birth reaching values found in adult liver after 2–3 months. Kidney has no more than trace amounts of cystathionine throughout development, higher activity of cystathionine synthase in the fetus than in the adult and high, unchanged activity of cystathionase throughout the period of development studied.

These results indicate that the high concentrations of cystathionine found in primate brain are reached postnatally and suggest that this high concentration of cystathionine may be associated with the functioning of mature brain.
ACETYLCHOLINE RECEPTORS: NUMBER and DISTRIBUTION IN INTACT and DEAFFERENTED SUPERIOR CERVICAL GANGLION OF THE RAT1
Authors: Fumagalli L. , De Renzis G. , Miani N.
Published: October 2006

Abstract—α‐Bungarotoxin (α‐BuTX) has been used as a marker for studying the acetylcholine receptors (AChRs) in the superior cervical ganglion (SCG) of the adult rat. Binding of [125I]α‐BuTX to detergent‐solubilized AChRs from rat SCG is a saturable and practically irreversible process. The rate constant of association of the toxin‐receptor complex is 1.66 × 105M−1S−1. The receptor is of nicotinic type. One SCG of adult rat binds about 57 fmol of [125I]α‐BuTX corresponding to 9.2 × 105AChRs per sympathetic neuron. Light microscope autoradiography shows that AChRs are mainly localized along neuronal processes (probably dendrites). The perikarya exhibit a weak radioactive reaction, while the nerve fibres are devoid of AChRs. Following preganglionic denervation the number of AChRs never increases and their spatial distribution seems not to change.
RAT BRAIN β‐GALACTOSIDASES: OBSERVATIONS ON CEREBROSIDE‐β‐GALACTOSIDASE CATALYSED TRANSGALACTOSYLATION AND COMPARISON OF ASSAY METHODS FOR SPHINGOLIPID HYDROLYSIS
Authors: Carter T. P. , Kanfer J. N.
Published: October 2006

Abstract— A partially purified rat brain preparation, enriched in cerebroside β‐galactosidase activity, was found to catalyze the synthesis of labelled galactosyl‐ceramide from [14C]oleoyl‐sphingosine as acceptor and several β ‐galactosides as donor. The following compounds in the order of their effectiveness served as galactose donors for this reaction: para‐nitrophenyl‐β ‐galactoside (PNP‐β ‐gal), galactosyl‐ceramide, lactosyl‐sphingosine, lactosyl‐ceramide, 4‐methyl‐umbelliferyl‐β ‐galactoside (4‐MU‐β ‐gal). asialo‐GM1, galactosyl‐sphingosine, GM1 and monogalactosyl‐diglyceride. It is believed that this transgalactosylation reaction is probably not a mere reversal of the hydrolytic reaction. Under optimal conditions the quantity of galactosyl‐ceramide formed represented 10% of the amount of donor hydrolysed. These observations in conjunction with those on the hydrolyses provide further support for the possible existence of two β ‐galactosidase isoenzymes involved with the catabolism of GM1 and/or lactosyl‐ceramide, and a single form for galactosyl‐ceramide. The activity of one isoenzyme can be ‘selectively’ measured simply by modifying the incubation mixture.
MECHANISM OF INTERACTION OF MYELIN BASIC PROTEIN AND S‐100 PROTEIN: METAL BINDING AND FLUORESCENCE STUDIES1,2
Authors: Perumal A. S. , Mahadik S. P. , Rapport M. M.
Published: October 2006

Abstract— It has been reported that myelin basic protein (MBP) forms a specific complex with S‐100 protein in the presence of either Ca2+ or Mn2+, as detected by Immunoelectrophoresis. We have now studied the binding of Ca2+ and Mn2+ to these two proteins. We find that MBP binds 1 mol of Mn2+/mol of protein, and this binding produces an increment in its fluorescence, indicating a conformational change. Ca2+ does not bind to MBP nor does it affect the fluorescence of MBP. S‐100 protein, as has been reported, binds about 10 mol of Ca2+/mol and this binding produces a conformational change. S‐100 protein also has 25 binding sites for Mn2+, but this binding does not alter fluorescence and does not appear to affect conformation. Competitive binding experiments demonstrate that the binding sites of S‐100 protein for Ca2+ and Mn2+ are independent. The alteration of electrophoretic migration in gels of S‐100 protein produced by Ca2+ and of MBP produced by Mn2+ are in accord with the observations based on fluorescence. Mn2+ does not affect the electrophoretic mobility of S‐100. These results indicate that the formation of the complex between MBP and S‐100 protein in the presence of either Ca2+ or Mn2+ is due to the conformational change induced by these ions in S‐100 protein, MBP, or both.
TISSUE DISTRIBUTION AND METABOLISM OF THE LATHYRUS SATIVUS NEUROTOXIN, L‐3‐OXALYLAMINO‐2‐AMINOPROPIONIC ACID, IN THE SQUIRREL MONKEY
Authors: Mehta T. , Zarghami N. S. , Cusick P. K. , Parker A. J. , Haskell Betty E.
Published: October 2006

Abstract– Although the L. sativus neurotoxin, L‐3‐oxalylamino‐2‐aminopropionic acid, is believed to cause neurological disease in humans, evidence that the toxin can enter the central nervous system except in animals with an immature or damaged blood‐brain barrier is lacking. Experiments described here suggest that an intraperitoneal dose of L‐3‐[14C‐oxalyl]amino‐2‐aminopropionic acid enters the central nervous system of young squirrel monkeys (Saimiri sciureus) whose blood‐brain barrier is mature. Most of the radioactivity recovered from monkey urine and tissues 1 h after injection was unchanged toxin. None was recovered in expired air as radioactive carbon dioxide.
ENZYMES ASSOCIATED WITH THE METABOLISM OF CATECHOLAMINES, ACETYLCHOLINE AND GABA IN HUMAN CONTROLS AND PATIENTS WITH PARKINSON'S DISEASE AND HUNTINGTON'S CHOREA
Authors: McGeer P. L. , McGeer E. G.
Published: October 2006

—Tyrosine hydroxylase (TH), dopa decarboxylase (DDC), glutamic acid decarboxylase (GAD), choline acetyltransferase (CAT), and acetylcholinesterase (AChE) were measured in 18–55 areas of brain from humans post mortem. Individuals meeting sudden and unexpected death (22), patients dying in hospital with non–neurological illness (6), Parkinson's disease (12), Huntington's chorea (8), terminal coma (6) or head injury (2) were included in the series. The absolute values obtained compared favourably with some previous human studies where high values for these enzymes were obtained, as well as with monkey and baboon data. The regional distributions of the enzymes were also comparable to those previously reported in human and animal studies. A number of important points with regard to human tissue seemed to emerge from the study. The mode of death was not a factor in enzyme levels in non–neurological and non‐coma cases. Post mortem delay did not seem to be a major factor either even though a substantial decline in GAD, TH and DDC could be demonstrated in rats left several hours between sacrifice and removal of the brain for assay. Age had a highly significant effect in certain areas of brain. The decline typically followed a curvilinear pattern (activity = A/age + B with the sharpest drops being in the younger age groups). DDC seemed to be the enzyme most severely affected by age but all the enzymes showed declines in certain brain areas, while in other areas there was no significant decline. All the enzymes were very depressed by coma from illness except AChE. TH and DDC in the brain stem were, however, not affected in the head injury cases. The Parkinsonian cases showed a sharply decreased TH activity in the substantia nigra, caudate and putamen. There were decreases in GAD in the globus pallidus (GP) and substantia nigra with marginal decreases in the neostriatum. CAT levels in the extrapyramidal nuclei were normal. In Huntington's chorea there was a substantial decrease in GAD in all the extrapyramidal structures. There was a patchy loss of CAT in the neostriatum and locus coeruleus.
THE SYNTHESIS OF BRAIN CHROMOSOMAL PROTEINS AFTER A PULSE OF THE NERVOUS SYSTEM‐SPECIFIC CARCINOGEN N‐ETHYL‐N‐NITROSOUREA TO THE FETAL RAT1,2
Authors: Biessmann H. , Rajewsky M. F.
Published: October 2006

Abstract— The synthesis of brain chromosomal proteins was investigated after a pulse of the nervous system‐specific carcinogen N‐ethyl‐N‐nitrosourea to the fetal BD IX‐rat. At different times up to 34 days after the carcinogen pulse, carcinogen‐treated and control brain cells were incubated for 6h with [14C] and [3H]leucine, respectively, in a standardized suspension culture system. The relative rates of leucine incorporation into histones F2a1, F2a2. and F3, and into 13 individual non‐histone chromosomal proteins, were measured after electrophoretic separation in 15% and 10% polyacrylamide gel, respectively. Both histone and NHP synthesis showed a biphasic response, with a common 2nd maximum as late as 15 days after the carcinogen pulse. A first peak of non‐histone chromosomal protein synthesis was seen at 24 h, when histone synthesis had not yet recovered from an initial 48 h depression. The data are discussed in relation to the possible regulatory role of chromosomal proteins in gene transcription during neoplastic transformation.
HYDROLYTIC AND TRANSGLUCOLYTIC ACTIVITIES OF A PARTIALLY PURIFIED CALF BRAIN β‐GLUCOSIDASE
Authors: Mumford R. A. , Raghavan S. S. , Kanfer Julian N.
Published: October 2006

Abstract— Properties of both a transglucosylation reaction and the hydrolytic activity of a partially purified calf brain β‐glucosidase were investigated. Sodium taurocholate and a ‘Gaucher factor’ stimulated both activities. A purified ‘stimulatory’ factor from human liver did not appear to significantly affect the hydrolytic activity towards either 4‐methylumbelliferone‐β‐d‐glucoside or [14C]glucosyl ceramide. Several compounds were found to be competitive inhibitors of the hydrolytic activity, conduritol B epoxide and norjirimycin being the most effective. Glucosyl ceramide hydrolysis was more sensitive to inhibition by p‐chloromercuribenzenesulfonate than 4‐methylumbelliferone‐β‐glucoside cleavage. The partially purified enzyme preparation catalyzed the formation of [14C]glucosyl ceramide with N‐[14C]oleoyl sphingosine as the acceptor and several β‐glucosides as the donor.
PRESENCE OF 15‐HYDROXY PROSTAGLANDIN DEHYDROGENASE, PROSTAGLANDIN‐Δ13‐REDUCTASE AND PROSTAGLANDIN E‐9‐KETO(α)‐REDUCTASE IN THE FROG SPINAL CORD
Authors: Bishai I. , Coceani F.
Published: October 2006

Metabolism of prostaglandin E1 (PGE1) and F1α (PGF1α) was studied in the frog spinal cord, using a hemisected preparation in vitro and tissue homogenates (whole honiogenate and tissue fractions). In the intact tissue, PGE, was converted to three Metabolites, 1 to 111, whereas only Metabolites 11 and 111 werc detected in experiments with PGF1α. Work with tissue homogenatcs confirmed that PG transformation is enzymatic, and endproducts were identified as PGF1α (Metabolite 1), 15‐kcto metabolite (Metabolite 11) and 15‐keto‐13,14‐dihydro metabolite (Metabolite 111). The 15‐keto‐13,14‐dihydro metabolite was formed via the 15‐keto metabolite which is consistent with findings elsewhere. These results establish the presence in the frog spinal cord of two pathways for PG metabolism, consisting one of the 15‐hydroxy prostaglandin dehydrogenase (15‐PGDH) and the prostaglandin‐A13‐ reductase (13‐PGR), the other of the prostaglandin E 9‐keto(α)‐reductase (9K‐PGR). 9K‐PGR is regarded as an inactivating enzyme because amphibian spinal neurons are less responsive to PGF, than to PGE1. In the intact or in the homogenized tissue, PGE, is metabolized more efficiently by the 15‐PGDH/13‐PGR than by the 9K‐PGR route. The 15‐PGDH metabolizes PGE, more readily than PGF1α. The present findings, together with the previous demonstration of active PG synthesis in the tissue and the potent actions of exogenous PGs, strongly suggest that the PGs play an important role in the function of neurons in the frog spinal cord.
HYPOXIC SURVIVAL OF NORMOGLYCAEMIC YOUNG ADULT AND ADULT MICE IN RELATION TO CEREBRAL METABOLIC RATES12
Authors: Berlet H. H.
Published: October 2006

The hypoxic tolerance and the cerebral metabolic rates (CMR) of young adult mice (20 to 25 g, 4 to 5 weeks old) and adult mice (30 g and above, 6 to 7 weeks old), respectively, were determined and their interrelationship was evaluated. CMRs increased from 25 mmol ‐ P/kg.min to 38 mmol/kg.min as the animals grew older from young to full adulthood. Concurrently the tolerance to aerogcnic hypoxia (5% O2‐95%j N2) declined. The effects of hypoxia on the cerebral energy metabolism were greater in adult than in young adult animals. It is concluded that the full metabolic maturation of the brain is reached in adult animals only. They become more dependent on an adequate oxygen supply as the aerobic activity of the energy metabolism of the brain is further increasing.

Hypoxic gasping occurred while the pool of cerebral energy reserves was still far from being depleted. A failure to utilize energy reserves rather than their exhaustion is suggested as the ultimate cause of death from hypoxia. An acid‐soluble form of glycogen or related polyglucan was found in addition to the usual amounts of insoluble glycogen. It was utilizcd rapidly during hypoxia and ischaemic anoxia and it may, therefore, constitute an additional source of carbohydrate substrates in thc brain.
STUDIES ON THE RELATIONSHIP BETWEEN GABA SYNTHESIS AND PROTEIN SYNTHESIS IN BRAIN
Authors: Sandoval Maríaa‐Elena , Palacios R. , Tapia R.
Published: October 2006

Abstract— The synthesis of γ‐aminobutyric acid (GABA) in mouse brain was decreased by treatment of the animals with pyridoxal phosphate‐ γ‐glutamylhydrazone, an inhibitor of glutamate decarboxylase in vivo. Under these experimental conditions the following parameters were studied: (1) the incorporation of labeled leucine in vivo, into protein of brain subcellular fractions; (2) the brain polysome profile; (3) the incorporation of labeled leucine into protein in vitro, in ribosomal preparations isolated from brain tissue. In other experiments, GABA synthesis was also decreased in brain cortex slices by preincubation with aminooxyacetic acid. The incorporation of [3H]leucine or [14C]leucine into protein in these slices was studied, and samples from the proteins were subjected to acrylamide‐sodium dodecylsulfate gel electrophoresis. Radioactivity was counted in slices of the gel. The results of the experiments in vivo and in vitro indicate that the previously reported decrease of protein synthesis induced by an inhibition of GABA synthesis affects proteins of all subcellular fractions and all populations of protein as separated by gel electrophoresis. The polysome profile from brains of mice with decreased GABA synthesis was similar to that of control mice. This result differs from that found when brain protein synthesis is inhibited by dopamine and serotonin.
GAS CHROMATOGRAPHY‐MASS FRAGMENTOGRAPHIC DETERMINATION OF INDOLE‐3‐ACETIC ACID IN RAT BRAIN
Authors: Warsh J. J. , Chan P. W. , Godse D. D. , Coscina D. V. , Stancer H. C.
Published: October 2006

Abstract— A gas chromatography‐mass fragmentographic procedure is described for the quantitation of indole‐3‐acetic acid (IAA) in rat brain. IAA was determined as its IV‐1‐pentafluoropropionyl‐methyl ester. Deuterium labeled IAA was employed as an internal standard. Assay sensitivities of at least 500 pg and 2.5 ng could be achieved by single and double ion monitoring respectively. Whole brain IAA concentrations were determined to be 11.6 + 0.75 ng/g (n = 6). IAA concentrations in brain areas ranged from 10 to 64 ng/g with highest levels in the striatum. Rat brain IAA accumulated curvilinearly with respect to time over a 90 min interval following probenecid (200 mg/kg, i.p.). The efflux of IAA from brain appears mediated in part through a probenecid‐sensitive active efflex process.
m‐OCTOPAMINE, p‐OCTOPAMINE AND PHENYLETHANOLAMINE IN RAT BRAIN: A SENSITIVE, SPECIFIC ASSAY AND THE EFFECTS OF SOME DRUGS
Authors: Danielson T. J. , Boulton A. A. , Robertson H. A.
Published: October 2006

Abstract— An enzyme radiochemical assay for p‐octopamine, m‐octopamine (norphenylephrine) and phenylethanolamine based on the N‐methylation of these amines by the enzyme phenylethanolamine N‐methyl transferase (S‐adenosyl‐l‐methionine: phenylethanolamine N‐methyl transferase (EC 2.1.1.28) has been developed. [3H]Methyl‐S‐adenosyl‐l‐methionine was used as methyl donor. The reaction products are converted to their dansyl derivatives and separated by TLC in three different solvent systems prior to liquid scintillation counting. The method exhibits a sensitivity of less than 10 pg for each amine and is suitable for the measurement of endogenous p‐octopamine levels in mammalian brain. The highest levels of p‐octopamine were found in the hypothalamus (3.4 ng/g) but despite the sensitivity of the assay, neither phenylethanolamine nor m‐octopamine could be detected. After MAO inhibition, however, both of these amines were found to be present. p‐Octopamine was increased substantially in all brain regions following the administration of an MAO inhibitor, whereas pretreatment with reserpine produced a significant decrease in the hypothalamus.