bluuebunny/crossref_metadata_2025_split huggingface dataset:
STUDIES ON THE MECHANISM OF DEMYELINATION: TRIETHYL TIN‐INDUCED DEMYELINATION
Authors: Smith Marion Edmonds 
Published: October 2006

AbstractThe metabolism of myelin undergoing breakdown as a result of edema induced by chronic administration of triethyl tin (TET) dissolved in the drinking water (10 mg/l.) was examined. The spinal cord showed more edema and loss of myelin than the brain. Uptake in vitro of [1‐14C]acetate into myelin lipids of slices of brain or spinal cord from TET‐treated rats was depressed until 4–5 weeks after the beginning of the regime, then rose to above normal levels. The uptake of [l‐14C]leucine into myelin protein rose within several weeks of TET treatment to levels averaging over 300 per cent of normal and remained high even after the TET was removed. The high levels of [l‐14C]leucine incorporation were inhibited by cycloheximide and were not explained by an increase in the size of the free amino acid pool. The three classes of myelin proteins, basic, proteolipid protein, and Wolfgram protein shared in the increased incorporation. Spinal cord myelin showed the greatest metabolic response, brain stem myelin less, and myelin from the forebrain was minimally affected by the TET treatment. Myelin prelabelled by intracisternal injection of [l‐14C]acetate and [l‐14C]leucine before the onset of TET administration showed faster turnover in myelin proteins in relation to the myelin lipids than the control in the most severely affected animals, but not in others less affected. A ‘floating fraction’ was observed floating on 10.5% (w/v) sucrose during the myelin purification. This fraction showed metabolic characteristics typical of myelin, and myelin‐labelling studies at various stages of the animal's development showed it to be derived from recently synthesized myelin. The floating fraction from the brain contained less cerebroside and more lecithin than myelin, while the spinal cord floating fraction composition was much like that of myelin. The floating fractions contained less protein typical of myelin (basic and proteolipid protein) and more highmolecular‐weight protein which may have been derived from contaminating microsomes. The floating fraction was presumed to be partially deproteinated myelin. The use of TET‐treatment as model for demyelination as a result of edema and proceeding in the absence of macrophages is discussed.
AXOPLASMIC TRANSPORT OF DOPAMINE IN NIGRO‐STRIATAL NEURONS1
Authors: Fibiger H. C. , McGeer E. G. , Atmadja S. 
Published: October 2006

AbstractThe possibility that dopamine is transported in the nigro‐striatal system was investigated by the stereotaxic injection of labelled tyrosine or l‐DOPA into the substantia nigra of tranylcypromine‐pretreated rats. At various intervals thereafter (2‐48 h), significant quantities of labelled material were recovered from the ipsilateral substantia nigra, globus pallidus and caudate‐putamen, The activity in the substantia nigra consisted of DOPA, dopamine, methoxytyramine, acid metabolites and other unidentified metabolites. In the caudate‐putamen, however, nearly all of the activity (85 per cent) was recovered in the dopamine fraction, the remainder being distributed among some of the metabolites. No DOPA was recovered from the caudate‐putamen. On the basis of time‐course studies after the injection of [14C]DOPA into the substantia nigra, we calculated the transport rate of dopamine in the nigro‐striatal bundle to be 0.8 mm/h. Electrolytic lesions of the nigrostriatal bundle at the level of the lateral hypothalamus, pretreatment with 6‐hydroxydopamine, or injections of [14C]DOPA dorsal to the substantia nigra each produced profound reductions in the amount of activity subsequently recovered from the caudate‐putamen. These data suggest that the activity recovered from the caudate‐putamen after injections of [14C]DOPA into the or substantia nigra reflected axonal transport rather than other processes such as diffusion or transport via the circulation. Pretreatment with the DOPA decarboxy‐lase inhibitor, Ro 4‐4602, significantly reduced the amount of activity recovered in the caudate‐putamen, an indication that decarboxylation of DOPA to dopamine was a prerequisite for transport. Pretreatment with reserpine also severely reduced the transport of dopamine in the nigro‐striatal bundle, an observation suggesting that dopamine was transported by binding to the amine storage granules. There was no evidence of retrograde transport of dopamine in the nigrostriatal bundle. Injections of larger than tracer quantities of labelled tyrosine into the substantia nigra did not produce the degree of transport of dopamine that was obtained after injections of DOPA, a result suggesting that the amine storage granules may not normally be filled during axonal transport.
BRAIN LIPIDS OF A CASE OF JUVENILE NIEMANN‐PICK DISEASE1
Authors: Tjiong H. B. , Seng P. N. , Debuch H. , Wiedemann H.‐R. 
Published: October 2006

Abstract—Lipids of frontal lobe grey and white matter were examined in parallel from a normal and a diseased child (M. Niemann‐Pick), both nine years of age.In the grey matter of the pathological case the following changes, although small, were found: a slight increase in all phospholipids and decreased values for nervonic acid in cerebrosides and for hydroxy fatty acids in sulphatides.White matter seemed much more affected by the disease: water content was about 6 per cent higher which corresponds to an approx. 20 per cent loss of dry substance compared with the normal brain. Further increases were observed in ‘ganglioside’ fraction and in all phosphatides. Cerebroside and sulphatide levels appeared decreased owing to destruction of myelin. In all of the glycerophosphatides oleic acid portions were lowered whereas in sphingolipids mainly nervonic acid values were reduced. Aldehyde content of both tissues seemed lowered in the disease, however, changes in composition were observed only in white matter, where the stearaldehyde portion of ethanolamine glycerophospholipid increased at the expense of palmitaldehyde and oleinaldehyde.
EFFECT OF THIAMINE DEPRIVATION AND THIAMINE ANTAGONISTS ON THE LEVEL OF γ‐AMINOBUTYRIC ACID AND ON 2‐OXOGLUTARATE METABOLISM IN RAT BRAIN12
Authors: Gubler C. J. , Adams B. L. , Hammond B. , Yuan En Chuan , Guo Shirley M. , Bennion M. 
Published: October 2006

AbstractBrain levels of y‐aminobutyric acid (GABA), glutamate and 2‐oxoglutarate, activities of glutamate decarboxylase GABA‐transaminase plus succinic semiaidehyde dehydrogenase and blood levels of glutamate and 2‐oxoglutarate were determined in normal, thiamine‐deprived, oxythiamine‐treated and pyrithiamine‐treated rats. Brain GABA levels were significantly reduced in thiamine‐deprived and pyrithiamine‐treated rats, but the activities of the enzymes of the GABA shunt pathway were not affected. Brain levels of glutamate were decreased and of 2‐oxoglutarate increased in all three types of deficiency. This was associated with similar decreases in glutamate and increases in 2‐oxoglutarate in the blood in all three deficient groups. Intraventricular injections of 2‐[U‐14C] oxoglutarate into the brain in these four groups of rats resulted in some significant differences in distribution of 14C in various TCA‐pathway intermediates and satellite compounds in the brain. Increases in 14C‐label were observed for glutamine and 2‐oxoglutarate in all three deficient groups as compared to controls. The 14C content of succinate, fumarate and aspartate was decreased in the thiamine deprived and PTh‐treated groups and [14C]glutamate was decreased in all three deficient groups. The 14C content of GABA was not significantly affected.
THE HALF‐LIFE OF ACETYLCHOLINESTERASE IN MATURE RAT BRAIN
Authors: Wenthold R. J. , Mahler H. R. , Moore W. J. 
Published: October 2006

Abstract—The rate of degradation of acetylcholinesterase [EC 3.1.1.7] in mature rat cerebral cortex was determined from the time course of the label introduced into the protein by one intraventricular injection of l‐leucine‐l‐14C. The half life of the enzyme was 2.84 ± 013 days.
ÈVIDENCE FOR THE COMPARTMENTATION OF GLUTAMATE METABOLISM IN ISOLATED RAT RETINA
Authors: Starr M. S. 
Published: October 2006

Abstract—Glucose is a major precursor of glutamate and related amino acids in the retina of adult rats. 14C from labelled glucose appears to gain access to a large glutamate pool, and the resulting specific activity of glutamate labelled from glucose is always higher than that of glutamine or the other amino acids.Radioactive acetate appeared to label a small glutamate pool. The specific activity of glutamine labelled from acetate relative to that of glutamate was always greater than 1.0. Other precursors of the small glutamate pool were found to include glutamate, aspartate, GABA, serine, leucine and sodium bicarbonate.The level of radioactivity present in retinae incubated with [U‐14C]glucose or [1‐14C]sodium acetate was reduced in the presence of 10−5m‐ouabain. Under these conditions, the relative specific activity of glutamine labelled from [1‐14C]sodium acetate was lowered, but it was raised when [U‐14C]glucose was used as substrate. Ouabain also considerably reduced the synthesis of GABA from [1‐14C]sodium acetate. In all cases ouabain caused a fall in the tissue levels of the amino acids.Aminooxyacetic acid (10−4m) almost completely abolished the labelling of GABA from both [U‐14C]glucose and [1‐14C]sodium acetate, while the RSA of glutamine labelled from the latter substrate was significantly increased. Aminooxyacetic acid raised the tissue concentration of glutamate, but caused a fall in the tissue concentrations of glutamine, aspartate and GABA.The results suggest that there are separate compartments for the metabolism of glutamate in retina and that these can be modified in different ways by different drugs.
CHANGES IN ENZYME PATTERNS PRODUCED BY HIGH POTASSIUM CONCENTRATION AND DIBUTYRYL CYCLIC AMP IN ORGAN CULTURES OF SYMPATHETIC GANGLIA1
Authors: Goodman R. , Oesch F. , Thoenen H. 
Published: October 2006

Abstract—Preliminary experiments had shown that acetylcholine, the putative mediator of trans‐synaptic induction of tyrosine hydroxylase (TH) and dopamine β‐hydroxylase (DBH) in vivo, did not lead to an increase in these enzyme activities in mouse superior cervical ganglia kept in organ culture. It was the aim of the present study to evaluate whether increases in tyrosine hydroxylase and dopamine β‐hydroxylase evoked by other stimuli such as potassium or dibutyryl cyclic AMP in such an in vitro system are representative for in vivo trans‐synaptic induction where changes in the levels of enzymes involved in norepinephrine synthesis or degradation are strictly confined to TH and DBH. In the presence of elevated concentrations of potassium or 5 mm dibutyryl cyclic AMP under organ culture conditions TH and DBH as well as DOPA decarboxylase and monoamine oxidase were significantly (P < 0.025) increased. The increase in total activities of TH and DBH were completely, those of DOPA decarboxylase and monoamine oxidase partially, inhibited by cycloheximide.In the presence of high concentrations of potassium, the total protein content of the ganglia was 28 per cent higher than in culture controls while dibutyryl cyclic AMP had no significant effect. Cycloheximide alone caused the protein content to fall to 70 per cent of that in control cultures. The loss of protein in the presence of cycloheximide was not accompanied by a simultaneous loss of TH, DOPA decarboxylase or monoamine oxidase, but DBH was decreased. Potassium was shown to increase the incorporation of [3H]leucine into TCA‐insoluble protein during an early culture period but dibutyryl cyclic AMP showed no such effect. An increase in the rate of incorporation of [3H]leucine into protein was seen in both the control and elevated potassium cultures after 48 h. This increase did not occur in the presence of dbcAMP.The difference in enzyme patterns under conditions of elevated potassium and dibutyryl cyclic AMP and the fact that no changes in the levels of endogenous cyclic AMP were observed during exposure to 54 mm‐potassium for a time period sufficient to initiate changes ultimately leading to elevated TH levels argues against the mediation of the potassium‐induced enzyme increases by cAMP.Since changes in enzyme patterns caused by potassium and dbcAMP were not similar to patterns seen in vivo under conditions of trans‐synaptic induction we conclude that use of this system as an in vitro model for in vivo trans‐synaptic induction necessitates great caution.
INCORPORATION OF 14C FROM [U‐14C]GLUCOSE INTO FREE AMINO ACIDS IN MOUSE BRAIN REGIONS UNDER CYANIDE INTOXICATION
Authors: Shimada M. , Kihara T. , Kurimoto K. , Watanabe M. 
Published: October 2006

Abstract—During anoxia induced by the administration of potassium cyanide, [U‐14C]glucose was injected intraperitoneally into adult mice and they were decapitated at 5, 15 and 30 min after the injection. After freeze‐drying in vacuo, differences in the uptake of radioactive carbon from [U‐14C]glucose into free amino acids (glutamate + glutamine, aspartate + asparagine, GABA, alanine and glycine) in mouse cerebral neocortex, cerebellar hemisphere, caudate nucleus, thalamus, hypothalamus and medulla oblongata were investigated (by macroautoradiography and GLC separation) and compared with those obtained under normal conditions.(1) During anoxia, autoradiographical densities in the thalamus and medulla oblongata were higher than that in the cerebral neocortex and caudate nucleus.(2) Among specific radioactivities (d.p.m./μmol) of free amino acids, alanine gave the highest value during anoxia, except in the cerebellar hemisphere and hypothalamus at 5 min and the medulla oblongata at 30 min.(3) During anoxia, the specific radioactivities of alanine and glycine in each brain region did not significantly decrease at 15 and 30 min compared with those under normal conditions. During anoxia, the specific radioactivity of glutamate + glutamine in the cerebellar hemisphere and hypothalamus did not significantly decrease compared with the normal conditions, while that of GABA, aspartate + asparagine and glutamate + glutamine in the cerebral neocortex, caudate nucleus, thalamus and medulla oblongata showed an increase.(4) The percentage decrease of glutamate + glutamine and aspartate + asparagine at 5 and 15 min was highly significant in the cerebral neocortex and caudate nucleus.
UTILIZATION OF ACETATE AND PYRUVATE FOR THE SYNTHESIS OF‘TOTAL’,‘BOUND’AND‘FREE’ACETYLCHOLINE IN THE ELECTRIC ORGAN OF TORPEDO
Authors: Israël M. , Tuček S. 
Published: October 2006

Abstract—Slices of tissue of the electric organ of Torpedo marmorata were incubated in vitro in a salineurea‐sucrose solution containing a labelled precursor of the acetyl moiety of ACh ([1‐14C]glucose, [2‐14C]pyruvate, or [1‐14C]acetate) either alone or in the presence of another unlabelled precursor. The incorporation of 14C from [1‐14C]acetate into ACh was considerably higher than from the other two substrates. The specific radioactivities (SRA) of the‘total',‘bound’and‘free’ACh were compared in experiments with [2‐14C]pyruvate and [1‐14C]acetate. With both precursors, the SRA of the‘bound’ACh were lower than those of‘total’ACh; consequently, the‘free’ACh pool was more labelled than the‘bound’pool. After short incubations with [2‐14C]pyruvate the SRA of'bound’ACh were closer to the SRA of‘total’ACh than with [1‐14C]acetate.A simple method is described for the labelling of ACh and its separation from other labelled compounds in experiments with the electric organ using [14C]acetate as the labelled precursor.
IN VIVO CHANGES OF CEREBRAL CYCLIC ADENOSINE 3′,5′‐MONOPHOSPHATE INDUCED BY BIOGENIC AMINES: ASSOCIATION WITH PHOSPHORYLASE ACTIVATION
Authors: Edwards C. , Nahorski S. R. , Rogers K. J. 
Published: October 2006

Abstract—The intravenous injection of adrenaline, isoprenaline and histamine to 4‐6‐day‐old chicks resulted in a rapid increase in the cyclic AMP content of cerebral hemispheres that had been removed and frozen within 0·5 s using a freeze‐blowing technique. Noradrenaline, dopamine, adenosine, 5‐HT and acetylcholine did not significantly alter the nucleotide concentration in vivo. Addition of adrenaline, isoprenaline and histamine to incubated chick cerebral cortex slices also increased the cyclic AMP content of the tissue. Noradrenaline was considerably less potent than these amines and adenosine was ineffective.Low phosphorylase a levels (16 per cent of total activity) were observed in instantaneously frozen cerebral hemispheres of untreated chicks. The injection of adrenaline, isoprenaline and histamine resulted in a rapid conversion of phosphorylase b to a and a significant fall in tissue glycogen. Administration of noradrenaline was without effect on the relative forms of phosphorylase and also failed to influence cerebral glycogen. Phosphorylase activation was not observed in chick cerebral slices under conditions producing large increases in cyclic AMP.It is suggested that in vivo phosphorylase activation and subsequent glycogenolysis may occur, at least in part, in glia and that these cells may be damaged during preparation of cerebral slices. The results provide evidence of a metabolic role for cyclic AMP in cerebral tissue.
INFLUENCE OF ANAESTHETICS ON THE BALANCE BETWEEN PRODUCTION AND UTILIZATION OF ENERGY IN THE BRAIN
Authors: Nilsson L. , Siesjö B. K. 
Published: October 2006

Abstract— The influence of general anaesthesia upon the metabolic state of the brain was evaluated from the tissue concentrations of ATP, ADP and AMP, and from the concentrations of glycolytic and citric acid cycle intermediates, in immobilized and artificially ventilated rats anaesthetized either with 70% N2O, 1% halothane or 60 mg/kg of pentobarbitone. The results were compared to the results obtained on awake animals in fentanyl‐analgesia. The adenylate energy charge was identical in all groups studied and there were no H+‐independent changes in the phosphocreatine/creatine ratios. In pentobarbitone anaesthesia there was an accumulation of glucose 6‐phosphate and a fall in fructose 1,6‐diphosphate, indicating inhibition of phosphofructokinase. No significant changes in these metabolites were observed with halothane or nitrous oxide anaesthesia and the substrate patterns differed from that obtained with pentobarbitone.The blood glucose concentrations were higher in the unanaesthetized, immobilized rats given fentanyl than in those anaesthetized. There was a direct relationship between the glucose concentrations in blood and in tissue. The glucose concentration ratios intracellular water to blood were higher in the anaesthetized than in the unanaesthetized animals, increasing with increasing depth of anaesthesia. The intracellular lactate concentrations were lowest in the groups given pentobarbitone and fentanyl citrate, and there was thus no direct relationship between lactate concentration and depth of anaesthesia.
IN VITRO EXPERIMENTS ON THE METABOLISM, ACCUMULATION AND RELEASE OF 5‐HT IN THE NERVOUS SYSTEM OF THE SNAIL HELIX POMATIA
Authors: Osborne N. N. , Neuhoff V. 
Published: October 2006

Abstract— The accumulation, metabolism and stimulated‐induced release of 5‐HT in the nervous system of the snail was studied. When nervous tissue was incubated at 24°C in a medium containing [14C]5‐HT or [3H]tryptophan, tissue: medium ratios of about 25:1 and 4:1 respectively were obtained after 45 min incubation.The process responsible for [14C]5‐HT accumulation showed properties of an active transport system: it was temperature sensitive and was greatly inhibited by dinitrophenol and ouabain. Furthermore, the accumulation process was inhibited by imipramine and desipramine.Of a number of analogues of indole, N‐acetyl‐5‐HT and 5‐hydroxytryptophan were the most potent in the inhibition of the accumulation of [14C]5‐HT. The presence of a large molar excess of amino acids had little effect.A small amount (less than 14 per cent) of the accumulated [14C]5‐HT was metabolized to form 5‐hydroxyindole acetic acid, even after long periods (2 h) of incubation. The accumulated [3H]tryptophan was metabolized to form 5‐hydroxytryptophan and 5‐HT; the content of formed [3H]5‐HT increased with incubation time whilst the [3H]5‐hydroxytryptophan remained more or less constant.The presence of p‐chlorophenylalanine in the incubation medium did not interfere with the accumulation of [3H]tryptophan, though it inhibited the formation of [3H]5‐hydroxytryptophan and to a greater extent [3H]5‐HT.A rapid efflux of the accumulated [14C]5‐HT from snail nervous tissue was observed on electrical stimulation. Slower release resulted when the Ca2+ ion content of the incubation medium was replaced by Mg2+ ions. There is also a slight efflux of radioactive substances following electrical stimulation in tissues previously incubated in [3H]tryptophan. Most of this radioactivity was attributed to the formed [3H]5‐HT.The data support the idea that 5‐HT is a transmitter‐substance in the snail Helix pomatia, and that re‐uptake of the substance is a method of inactivating the released amine.
RNA METABOLISM IN ISOLATED MOUSE BRAIN NUCLEI DURING EARLY POSTNATAL DEVELOPMENT
Authors: Banks‐Schlegel S. P. , Johnson T. C. 
Published: October 2006

Abstract—RNA metabolism in isolated brain nuclei has been shown to be dramatically altered during early postnatal brain development. The present study involved an examination of the RNA products synthesized by nuclei at various stages of postnatal neural maturation. In all cases, the majority of the RNA appeared to be heterodisperse, non‐ribosomal and non‐tRNA in nature. In comparison to the RNA isolated from nuclei of neonatal tissue, the RNA from nuclei of 12‐day and 30‐day‐old mouse brain was found to be of smaller molecular weight. Despite the heterodisperse nature of these RNA molecules, the addition of α‐amanitin did not completely inhibit nuclear synthesis.An investigation of RNA synthesis in isolated neuronal and glial cell nuclei revealed that nucleic acid metabolism in these respective cell populations had different and distinct developmental patterns. Preparations enriched with glial cell nuclei were found to be most active at birth and then decreased in activity (3–4‐fold) during neural maturation. On the other hand, the rate of RNA synthesis in fractions enriched in neuronal cell nuclei was observed to increase dramatically in activity (4–5‐fold) until 14 days of age. From 14 days of age until adulthood, RNA synthetic activity remained essentially the same.
THE EFFECTS OF SOME NEWER ANAESTHETICS ON THE IN VITRO ACTIVITY OF GLUTAMATE DECARBOXYLASE AND GABA TRANSAMINASE IN CRUDE BRAIN EXTRACTS AND ON THE LEVELS OF AMINO ACIDS IN VIVO
Authors: Dye D. J. , Taberner P. V. 
Published: October 2006

Abstract—The effects of several anaesthetic and hypnotic compounds with well‐defined excitatory side‐effects on glutamate decarboxylase and γ‐aminobutyric acid transaminase activity have been examined. The dissociative anaesthetics ketamine and γ‐hydroxybutyric acid produced competitive inhibition of glutamate decarboxylase with respect to glutamate at concentrations which had no effect on GABA transaminase activity. The inhibitor constant (Ki) values were, ketamine: 13.3 mm, γ‐hydroxybutyric acid; 8.8 mm. The steroid anaesthetic alphaxalone was also a potent competitive inhibitor of glutamate decarboxylase Ki= 4.1 mm). Pentobarbitone, thiopentone and methohexitone non‐competitively inhibited both glutamate decarboxylase and GABA‐transaminase but only at high concentration (> 20 mm). None of the drugs tested produced any significant change in brain GABA or glutamate levels following the injection of an hypnotic or anaesthetic dose. It is proposed that an alteration in the rate of GABA synthesis as a result of the inhibition of glutamate decarboxylase could explain the convulsive properties of the dissociative anaesthetics when given at high doses.