bluuebunny/crossref_metadata_2025_split huggingface dataset:
DYNAMICS OF CEREBRAL METABOLISM DURING MODERATE HYPERCAPNIA1
Authors: Kogure K. , Busto R. , Scheinberg P. , Reinmuth O. 
Published: October 2006

Abstract—The effects of hypercapnia on the kinetics of cerebral energy metabolism were evaluated in adult rats by the closed system method of LOWRY et al. (1964). Moderate hypercapnia with a Paco2 of 61 torr sustained for 20 min resulted in intracellular brain acidosis (7.07‐6.97). During hypercapnia the tissue content of glucose increased whereas phosphocreatine, ADP, pyruvate and lactate contents, and the lactate/pyruvate ratio decreased. The ATP/ADP ratio increased from 7.7 to 9.0; the cytoplasmic NADH/NAD + ratio decreased from 2.06 × 10‐3 to 1.49 × 10‐3. There was no change in Energy Charge. Turnover rate of phosphocreatine increased from 3.84 to 4.62 mmol/kg/min, but the turnover rates of ATP, glucose and glycogen were reduced (from 1.98 to 1.86, 6.24 to 4.80, and 3.96 to 2.94 mmol/kg/min, respectively). The utilization rate of total high energy phosphate decreased from 30.6 to 25.4 mmol/kg/min while the post‐decapitation EEG during hypercapnia persisted longer than during normocapnia. These results indicate that moderate hypercapnia reduces the overall kinetic activity of cerebral energy metabolism. The steady Energy Charge suggests that the reduction in the rate of high energy phosphate use is proportionally balanced by a lowered production rate of ATP.
SPINAL CORD LIPIDS AND MYELIN COMPOSITION IN BORDER DISEASE (HYPOMYELINOGENESIS CONGENITA) OF LAMBS
Authors: Patterson D. S. P. , Terlecki S. , Foulkes J. A. , Sweasey D. , Glancy E. M. 
Published: October 2006

Abstract—Spinal cords from clinically affected newborn lambs, each with muscular spasms (‘shaking’) and a ‘hairy’ birth coat, were found to be deficient in DNA and to contain less myelin and various lipid components, suggesting retarded CNS development equivalent to about 124 days conceptual age. Cerebrosides were notably deficient in whole cord and isolated myelin and contained more saturated and less unsaturated fatty acids than normal. The rate of cerebroside synthesis assayed in vitro was enhanced and taken with the very low tissue concentrations this indicated faster cerebroside turnover and a less stable myelin in the spinal cords of lambs affected with Border Disease. Marked decreases in plasmalogen concentrations, the redistribution of phospholipid fractions, the presence of about 8 per cent cholesterol in the esterified form and the characteristic fatty acid composition of these esters strongly suggest that degeneration is concomitant with myelin immaturity. Hypocupraemia, low concentrations of copper in the cerebrum and increased concentrations in spinal cord myelin are additional features of the clinical disease. The latter result may be related to myelin immaturity.
EVIDENCE FOR A SINGLE CATALYTIC BINDING SITE ON HUMAN BRAIN TYPE B MONOAMINE OXIDASE
Authors: Roth J. A. 
Published: October 2006

Abstract—The tricyclic antidepressant drug, amitriptyline, inhibited the B form of human brain mitochondria] monomine oxidase (MAO) under normal atmospheric conditions in a noncompetitive manner when phenylethylamine (PEA) was used as substrate and competitively when benzylamine (BzNH2) was employed as substrate. In addition, it was also found that PEA and BzNH2 inhibited each other's degradation noncompetitively. Similar results have previously been reported with human platelet MAO. These data suggest that the catalytic binding sites for PEA and BzNH2 on the B form of human brain MAO may be different. Attempts were made to further distinguish these catalytic binding sites on the brain oxidase using the irreversible MAO inhibitors, pargyline and clorgyline. Though these drugs have considerably different affinities for the B form of the oxidase, the degree to which either compound inhibited PEA or BzNH2 deamination was essentially identical. When incubations were performed at elevated oxygen concentrations PEA and BzNH2 became mutually competitive inhibitors of each other's metabolism. Also at the higher levels of oxygen, amitriptyline inhibition of PEA deamination approached a competitive fashion. These results suggest that PEA and BzNH2 share a common catalytic binding site on the B form of MAO and, in addition, bind to an inhibitory site on the reduced form of the oxidase. Accordingly, the data indicate that amitriptyline also binds to both the oxidized and reduced forms of this human brain oxidase.
NEUROTOXICITY OF A NON‐METABOLIZABLE AMINO ACID, 1‐AMINOCYCLOPENTANE‐l‐CARBOXYLIC ACID: REGIONAL PROTEIN LEVELS AND LIPID COMPOSITION OF NERVOUS TISSUE
Authors: Nixon R. A. 
Published: October 2006

Abstract— The non‐metabolizable amino acid, 1‐aminocyclopentane‐l‐carboxylic acid (ACPC), when administered to mice, induces primary degeneration of axons in the cerebellum, rostral spinal cord and peripheral nerves. One to 4 weeks after a single intraperitoneal injection of ACPC (0.5–2 mg/g body wt) in adult mice, the fresh and dry weights of brain, cerebellum and spinal cord were reduced compared with those of normal and pair‐fed controls. The protein content of all CNS regions, but particularly that of the cerebellum and cervical spinal cord, was lowered in ACPC‐treated mice relative to that of normal controls. Sciatic nerve protein was also decreased in mice following 2 mg/g of ACPC. Pair‐fed controls exhibited protein deficits in the cerebellum and cervical spinal cord but to a significantly smaller degree. In ACPC‐treated mice, the sulfatide content of spinal cord and peripheral nerve was reduced but that of brain was normal. Sphingomyelin levels in these three regions increased except in the brains of mice given 0.5 mg/g of ACPC where the levels fell.The protein and sulfatide deficits were greatest in the regions which are known to exhibit the highest proportion of degenerating nerve fibers. The correlation of ACPC treatment with protein and sulfatide loss is consistent with the reported disruptive effects of ACPC on protein metabolism and with the involvement of proteins in sulfatide. metabolism. The protein deficits in pair‐fed mice are considered in relation to the exacerbating effect of reduced dietary protein intake on ACPC neurotoxicity.
CONTENTS OF SEVERAL AMINO ACIDS IN THE CEREBELLUM, BRAIN STEM AND CEREBRUM OF THE ‘STAGGERER’, ‘WEAVER’ AND ‘NERVOUS’ NEUROLOGICALLY MUTANT MICE1
Authors: McBride W. J. , Aprison M. H. , Kusano K. 
Published: October 2006

Abstract—The content of glutamate, GABA, aspartate, glycine and alanine was determined in the cerebellum, brain stem and cerebrum of three different mutant mice which have been named ‘staggerer’, ‘weaver’ and ‘nervous’ on the basis of neurological symptoms. In the ‘staggerer’ and ‘weaver’ mutants there is an almost complete absence of granule cells in the cerebellar cortex while in the ‘nervous’ mutant there is a loss of Purkinje cells (and to a lesser extent a loss of granule cells) in the cerebellar cortex. In the cerebellum of the ‘weaver’ mutant, the content of glutamate was signficantly lower (P < 0.025) than control values (8.77 ± 0.76 vs 12.0 ± 1.3 μmol/g tissue wet wt) and the contents of GABA and glycine were significantly greater than normal levels. In the cerebellum of the ‘staggerer’ mutant, the content of glutamate was significantly lower (6.62 ± 0.70 μmol/g) and the contents of glycine and alanine significantly higher than control values. In the cerebrum and brain stem regions of the staggerer mutant, weaver mutant and the normals the contents of the five amino acids were the same. The contents of glycine and alanine in the cerebellum, GARA and glycine in the brain stem and GABA and alanine in the cerebrum of the nervous mutants were higher than control values. The data are discussed in terms of a possible role for glutamate functioning as an excitatory transmitter when released from the cerebellar granule cells.
DIFFERENTIAL DISTRIBUTION OF [U‐14C]GLUCOSE AND [U‐14C]GLYCEROL AMONG MOLECULAR SPECIES OF PHOSPHATIDYL CHOLINE, PHOSPHATIDYL ETHANOLAMINE AND 1,2‐DIACYLGLYCEROL IN RABBIT BRAIN12
Authors: Bralining Christiane , Gercken G. 
Published: October 2006

AbstractSpecific radioactivities of molecular species of phosphatidyl choline(PC), phosphatidyl ethanolamine(PE) and 1,2‐diacylglycerol were determined in rabbit brain 15 and 30 min after intraventricular injection of 10OpCi of either [U‐14C]glucose or [U‐14C]glycerol. The rate of de nouo synthesis of glycerophospholipids and their molecular species could be determined after glycerol labelling, since 94.0–99.7% of 14C activity was recovered in glyceryl moieties of brain lipids. After injection of glucose radioactivity was measured in both glyccrol and acyl residues of lipids.High incorporation rates were measured in species of PC, PE and 1,2‐diacylglycerol with oleic acid in position 2 and with palmitic, stearic or oleic acids in position 1. The conclusion may therefore be drawn that these molecular species were preferably synthesized de novo by selective acylation of glycerol 3‐phosphate. The lowest specific activities were observed for 1,2‐dipalmitoyl‐ and l‐stearoyl‐2‐ arachidonoyl‐glycerol, ‐PC and ‐PE. These turnover rates point to incorporation of arachidonate, and probably also of palmitate in dipalmitoyl‐PC, amounting to 20% of total PC, via deacylation‐acylation‐ cycle.
EFFECTS OF CALCIUM AND MAGNESIUM DEFICIENCY ON THIAMINE DISTRIBUTION IN RAT BRAIN AND LIVER
Authors: KIMURA M. , ITOKAWA Y. 
Published: October 2006

Abstract—Wistar rats were divided into 4 groups and the following different synthetic diets were given for 1 month: group 1, calcium‐ and magnesium‐deficient; group 2, calcium‐deficient, magnesium‐sufficient; group 3, calcium‐sufficient, magnesium‐deficient; group 4, calcium‐sufficient, magnesium‐sufficient (normal diet). After 1 month on these dietary regimens, the rats were killed. In calcium‐deficiency (groups 1 and 2), thiamine concentration in synaptosomal and myelin‐membrane fractions in the brain had decreased and the ratio of free thiamine to total thiamine and non‐protein bound thiamine amount had increased in the brain. In magnesium‐deficiency (groups 1 and 3), thiamine concentration in the liver and activities of thiamine‐dependent enzymes in liver had decreased. These results indicate that calcium plays a role in binding thiamine in nerve membrane structures, which have a specific role in the conduction process of nervous tissues. In contrast, magnesium has little effect on thiamine in nervous tissues but may play an important role in thiamine‐dependent enzyme systems in the liver.
PURIFICATION AND PROPERTIES OF HUMAN BRAIN α‐L‐FUCOSIDASE
Authors: ALHADEFF J. A. , JANOWSKY A. J. 
Published: October 2006

Abstract—Human brain α‐L‐fucosidase has been extracted and the soluble portion has been purified 9388‐fold with 25% yield by a two‐step affinity chromatographic procedure utilizing agarose‐epsilon‐aminocaproyl‐fucosamine. Isoelectric focusing revealed that all seven isoelectric forms of the enzyme were purified. Trace amounts of eight glycosidases, with hexosaminidase being the largest contaminant (1% by activity) were found in the purified α‐L‐fucosidase preparation. Sodium dodecyl sulfate‐polyacrylamide gel electrophoresis indicated the presence of a single subunit of molecular weight 51,000 ± 2500. The purified enzyme has a pH optimum of 4.7 with a suggested second optimum of 6.6. The apparent Michaelis constant and maximal velocity of the purified enzyme with respect to the p‐nitrophenyl substrate are 0.44 mM and 10.7 μmol/min/mg protein, respectively. Ag2+ and Hg2+ completely inactivated the enzyme at concentrations of 0.1‐0.3 mM. Antibodies made previously against purified human liver α‐L‐fucosidase cross‐reacted with the purified brain α‐L‐fucosidase and gave a single precipitin line coincident with that from purified liver α‐L‐fucosidase. From all our studies it appears that at least the soluble portion of brain α‐L‐fucosidase is identical to human liver α‐L‐fucosidase.
CHARACTERIZATION OF PUTATIVE AMINO ACID TRANSMITTER RELEASE FROM SLICES OF RAT DENTATE GYRUS
Authors: Nadler J. V. , White W. F. , Vaca K. W. , Redburn Dianna A. , Cotman C. W. 
Published: October 2006

Abstract— Superfused slices of the rat dentate gyrus were employed to study the release of GABA, glutamate and aspartate, which are considered strong neurotransmitter candidates in this region. The introduction of Ca2+ to a Ca2+‐free superfusion medium containing a depolarizing agent augmented the efflux of all three amino acids. The response to application of Ca2+ nearly always occurred within 30 s, the shortest interval tested in these studies. The efflux rate reached a peak within 90 s and then declined to a level slightly greater than the prestimulation baseline. The failure to maintain the maximal rate with continued exposure to Ca2+ and depolarizing influences appeared not to result from a reduction in Ca2+ permeability caused by continuous depolarization. Ca2+ also stimulated the efflux of exogenously loaded radiolabeled GABA, glutamate and aspartate, but not proline. Exogenously loaded GABA was more readily released than endogenous GABA. Otherwise the effects of various treatments on their efflux rates were qualitatively similar.Mg2+ inhibited Ca2+‐dependent efflux. Ba2+, but not Mg2+, stimulated amino acid efflux in the absence of Ca2+. Extracellular Na+ was not required to support Ca2+‐dependent efflux. Addition of Ca2+ to a Ca2+‐free medium in the absence of a depolarizing agent released GABA from the slices, but not glutamate or aspartate.K+‐enriched medium and the depolarizing alkaloid, veratridine, stimulated both Ca2+‐dependent and Ca2+‐independent release processes. Na+‐free medium enhanced the Ca2+‐independent releasing action of elevated K+. Ca2+‐independent release was inhibited by raising the Mg2+ concentration by 15 or 30 mM and appeared to be inhibited by Ca2+ as well. Amino acid output in the absence of Ca2+ is probably not directly related to transmission and is considered to result partially from a general increase in membrane permeability induced by depolarization in a Ca2+‐free medium and partially from stimulation of carrier‐mediated amino acid efflux.These results support previously suggested transmitter roles for GABA, glutamate and aspartate in the rat dentate gyrus.
STUDIES OF THE INTER‐RELATIONSHIP BETWEEN CEREBROSPINAL FLUID AND PLASMA AMINO ACID CONCENTRATIONS IN NORMAL INDIVIDUALS
Authors: McGale E. H. F. , Pye I. F. , Stonier C. , Hutchinson E. C. , Aber G. M. 
Published: October 2006

Abstract— —The concentration of free amino acids has been determined in lumbar CSF in 37 fasting normal subjects. The values obtained have been compared with the concentration of the same amino acids measured in venous plasma collected simultaneously and with ventricular CSF amino acid concentrations. Twenty‐three amino acids have been identified and quantitated in CSF and plasma. Trace quantities of eight other amino acids have been also detected.The concentration of 13 amino acids in CSF has been shown to be directly related to the plasma concentration. No such relationship was noted for the other 7 amino acids. Significant variations in the concentration of individual amino acids relating to both age and sex have been noted. A large number of unidentified ninhydrin positive compounds have been found in CSF. Preliminary studies have identified one of these as ɛ‐aminobutyric acid (GABA).
RAT BRAIN SYNAPTIC VESICLES: UPTAKE SPECIFICITIES OF [3H]NOREPINEPHRINE AND [3H]SEROTONIN IN PREPARATIONS FROM WHOLE BRAIN AND BRAIN REGIONS1
Authors: Slotkin Theodore A. , Seidler Frederic J. , Whitmore William L. , Lau Christopher , Salvaggio Maria , Kirksey Donny F. 
Published: October 2006

AbstractA fraction containing neurotransmitter storage vesicles was isolated from rat whole brain and brain regions, and the uptakes of [3H]norepinephrine and [3H]serotonin were determined in vitro. Norepinephrine uptake in vesicle preparations from corpus striatum was higher than in prep arations from cerebral cortex, and uptake in vesicles from the remainder (midbrain + brainstem + cerebellum) was intermediate. The Km for norepinephrine uptake was the same in the three brain regions, but the regions differed in maximal uptake capacity by factors which paralleled total catecholamine concentration rather than content of norepinephrine alone. Intracisternal administration of 6‐hydroxydopamine, but not of 5,6‐dihydroxytryptamine, reduced vesicular norepinephrine uptake, and pretreat‐ment with desmethylimipramine (which protects specifically norepinephrine neurons but not dopamine neurons from the 6‐hydroxydopamine) only partially prevented the loss of vesicular norepinephrine uptake. These studies indicate that uptake of norepinephrine by rat brain vesicle preparations occurs in vesicles from norepinephrine and dopamine neurons, but probably not in vesicles from serotonin neurons. Uptake of serotonin by brain vesicle preparations exhibited time, temperature and ATP‐Mg2+ requirements nearly identical to those of norepinephrine uptake. The affinity of serotonin uptake matched that of serotonin for inhibition of norepinephrine uptake, and the maximal capacity was the same for serotonin as for norepinephrine. Norepinephrine, dopamine and reserpine inhibited serotonin uptake in a purely competitive fashion, with Kis similar to those for inhibition of norepinephrine uptake. Whereas 5,6‐dihydroxytryptamine treatment reduced synaptosomal serotonin uptake but not vesicular serotonin uptake, 6‐hydroxydopamine reduced vesicular serotonin uptake in the absence of reductions in synaptosomal serotonin uptake. Thus, in this preparation, serotonin appears to be taken up in vitro into catecholamine vesicles, rather than into serotonin vesicles.
CEREBRAL METABOLIC AND CIRCULATORY CHANGES INDUCED BY HYPOXIA IN STARVED RATS
Authors: Berntman L. , Siesjou B. K. 
Published: October 2006

AbstractIn order to study cerebral metabolic and circulatory effects of hypoxia under conditions of restricted glucose supply, the arterial Po2, was reduced to 25–30mm Hg in artificially ventilated and lightly anaesthetized rats that were starved for 24 or 48 h prior to experiments. Arterial glucose concentrations, that were initially around 6μmol g‐1, were significantly reduced after 15min of hypoxia, and decreased to 50o of control after 30min.In animals studied after 30min of hypoxia (24 h of starvation), cerebral blood flow had increased 4‐fold and there was a moderate (25%) rise in cerebral oxygen consumption. During the course of hypoxia, cerebral cortical concentrations of glucose fell to low values. In spite of this, concentrations of pyruvate and lactate rose with time, and the sum of citric acid cycle intermediates (citrate, α‐ketoglutarate, fumarate. malate and oxaloacetate) increased. Changes in amino acids were dominated by a fall in aspartate and a rise in alanine concentration. There was a moderate reduction in phosphocreatine and a slight rise in ADP concentration, but concentrations at ATP and AMP were unchanged. The changes observed are similar to those previously obtained in fed animals. It is concluded that even if blood glucose concentrations fall to 3μmol g‐1, and cerebral energy flux is maintained, substrate supply is sufficient to cover the energy requirements of the tissue.Hypoxia was accompanied by increases in the lactate/pyruvate and β‐hydroxybutyrate acetoacetate ratios of blood. In the tissue, NADH/NAD+ ratios derived from the lactate, malate and β‐hydroxybutyrate dehydrogenase systems rose, while that derived from the glutamate dehydrogenase reaction fell. It is concluded that the latter system is not well suited for estimating mitochondrial redox changes in brain tissue.
PROLIDASE ACTIVITY IN BRAIN: COMPARISON WITH OTHER ORGANS
Authors: Hui K. S. , Lajtha A. 
Published: October 2006

Abstract—Prolidase (imidodipeptidase, EC 3.4.3.7) activity in brain was assayed spectrophotometrically, and the validity of the assay was confirmed by microchromatographic analysis of the dansyl derivatives of the reaction products. The ratio of the activity of prolidase from brain on Ala‐Pro, Gly‐Pro, and Pro‐Pro was similar to that of the highly purified intestinal mucosal prolidase. The size and polarity of the amino acid side chain (R) of the N‐terminal amino acid and whether the terminal amino and carboxy groups are free or blocked are important factors in determining prolidase substrate activity. Using Ala‐Pro as substrate, we found prolidase activity in all rat tissues we investigated, with highest activity in kidney and lowest in plasma; 33 mmol of Ala‐Pro was hydrolyzed per mg of protein per min by brain tissue, which is 20% of the activity for kidney and 23% of that for intestinal mucosa. The specific activity of prolidase was higher in the sciatic nerve than in brain or spinal cord, and activity was higher in the distal portion.
EFFECT OF 1‐AMINOCYCLOPENTANE‐1‐CARBOXYLIC ACID (CYCLOLEUCINE) ON DEVELOPING RAT CENTRAL NERVOUS SYSTEM PHOSPHOLIPIDS
Authors: Ramsey Robert B. , Fischer Vernon W. 
Published: October 2006

Abstract—Treatment of developing rats with 1‐amino‐cyclopentane carboxylic acid (cycloleucine) resulted in changes in brain and spinal cord phospholipid content and fatty acid composition. General findings were a decrease in ethanolamine phospholipid content, and relative increase in the saturated fatty acid content of ethanolamine phospholipid. In all the different cycloleucine experiments conducted, there was consistently less fatty aldehyde present in the methylated ethanolamine phospholipid fatty acid‐fatty aldehyde fractions than in corresponding controls. In some experiments fatty aldehyde was almost completely absent, suggesting the presence of little plasmalogen. Changes in fatty acids of phosphatidyl choline, the other phospholipid examined in this manner, were generally minor. Administration of massive amounts of sodium propionate in addition to cycloleucine did not result in an appreciable odd‐chain fatty acid increase in the CNS.Examination of the spinal cords by electron microscopy demonstrated considerable myelin splitting in one set of animals. No other ultrastructural changes were evident.The suitability of this drug to produce a neurological condition and pathological state similar to that seen in B12‐deficient subacute combined degeneration is discussed.
DISTRIBUTION OF VASOACTIVE INTESTINAL POLYPEPTIDE (VIP) IN THE PORCINE CENTRAL NERVOUS SYSTEM
Authors: Fahrenkrug J. , de Muckadell O. B. Schaffalitzky 
Published: October 2006

Abstract—A sensitive and specific radioimmunoassay for vasoactive intestinal polypeptide (VIP) has been used to determine the regional distribution of the peptide in the porcine CNS. The hippocampus and cerebral cortex contained the highest concentration of VIP, while lower but significant amounts were present in the hypothalamus and neurohypophysis. The immunoreactive VIP in the brain appeared to be identical with the octacosapeptide originally isolated from porcine small intestine, since it was found to have identical chromatographic properties. to dilute in parallel with the standard curves and to react equally with six different VIP antisera independent of extraction procedure used.