bluuebunny/crossref_metadata_2025 huggingface dataset:
CEREBRAL ENERGY METABOLISM DURING EXPERIMENTAL STATUS EPILEPTICUS1
Authors: Duffy T. E. , Howse D. C. , Plum F.
Published: October 2006

—The concentration of ATP, ADP, AMP, phosphocreatine and of 5 intermediates of carbohydrate metabolism were determined in rodent brain after single and repeated seizures induced by either electroshock (ES), flurothyl or pentylenetetrazol (PTZ). In paralysed‐ventilated rats, one ES produced a 4–5 fold increase in cortical glycolytic flux (estimated from changes in glucose and lactate), and associated increases in pyruvate and in the lactate/pyruvate ratio. Total high energy phosphates declined during the seizure; a decrease was also calculated in cortical tissue pH and in the cytoplasmic [NAD+]/[NADH] ratio. Similar changes in brain were observed in ventilated mice after ES, but in paralysed animals, no decrease in high energy phosphates occurred during the first seizure. More vigorous and prolonged chemically‐induced seizures in both rats and mice elicited a decrease in the cerebral energy reserves with a rise in lactate and in the lactate/pyruvate ratio. At all times during the seizures the cerebral venous blood had a higher oxygen tension than that of control animals (rats) or was visibly reddened (mice), implying that oxygen availability to brain exceeded metabolic demands. It is proposed that the development of‘non‐hypoxic’cerebral lactacidosis during seizures is part of the overall metabolic response of the brain to an abrupt increase in energy consumption. The response constitutes a homeostatic influence which promotes cerebral vasodilatation, thereby increasing blood flow and the delivery of substrates.

With repeated seizures, delivered 2 min apart, glycogen declined progressively, but concentrations of the adenine nucleotides appeared to plateau, suggesting that a new energy balance had been established. However, after 20–25 seizures, the attacks became self‐generating and there was a further reduction in the tissue high energy phosphate stores, a fall in brain glucose and in the brain/blood glucose ratio. It is concluded that the brain possesses a limited capacity to adjust its metabolism to meet the increased energy requirements of single or repeated seizures, but that this mechanism ultimately fails during status epilepticus unless the abnormal electrical discharges, themselves, are brought under control.
THE DISTRIBUTION OF GLUTAMATE DECARBOXYLASE IN RAT TISSUES; ISOTOPIC VS FLUORIMETRIC ASSAYS
Authors: MacDonnell P. , Greengard O.
Published: October 2006

—The activity of glutamate decarboxylase (GAD, EC 4.1.1.15) in normal and neoplastic rat tissues was determined by two assay methods, one based on the production of 14CO2 from [14C]glutamic acid and the other on the fluorimetric measurement of γ‐aminobutyric acid (GABA) formation. Activities obtained with the isotopic assay were high in every tissue (ranging from over 800 in liver and brain to 107nmol CO2/min/g in lung). They were drastically diminished by Triton X‐100, by an oxygen‐free atmosphere or by the mitochondrial electron transport inhibitors, rotenone and antimycin A. Activities measured fluorimetrically were significant in only a few tissues and were stimulated by Triton (e.g. from 299 to 569 nmol GABA/min/g brain) but were unaffected by rotenone. For several tissues after Triton treatment the fluorimetric and isotopic assays (in air) gave the same results (i.e. the two end products, CO2 and GABA were in stoichiometric agreement); however, the fluorimetric assay remains the more reliable measure of GAD activity since Triton may not inhibit completely the non‐GAD dependent decarboxylation of glutamate in all types of tissue preparations. The hepatic, renal and mammary tumours tested were devoid of GAD; among non‐neural normal tissues, kidney, liver and, possibly, adrenal gland contained significant GAD activity. In kidney and liver the activity was 15 and 10 per cent of that in brain.
IMMUNOLOGICAL STUDIES OF THE RAT OLFACTORY MARKER PROTEIN1
Authors: Keller Angelica , Margolis F. L.
Published: October 2006

Abstract— Antisera against the rat olfactory marker protein were prepared by injection of the homogeneous protein into a goat and a rabbit. When the antisera were tested by immunodiffusion against olfactory tissue extracts, many but not all mammalian species cross‐reacted against these antisera. Immunoprecipitin titrations with the goat antiserum generally showed higher cross‐reactivity against olfactory extracts from species more closely related to the rat. Human olfactory bulb extracts and non‐mammalian olfactory tissue extracts did not cross‐react with the antisera by either immunodiffusion tests or immunoprecipitin titrations, however, they did cross‐react when tested by a competitive binding radioimmunoassay using tritium‐labelled purified rat protein and the goat antibody.

The olfactory marker protein which is an example of a brain protein specific to one cell, the olfactory chemoreceptor neuron, has a very wide species distribution, being present in rat, mouse, hamster, guinea‐pig, sheep, cow, rabbit, pig, dog, man, frog and garfish. Therefore it presumably plays an important and unique role related to the function of this primary chemosensory neuron.
DECREASED RATE OF GLUCOSE UTILIZATION BY RAT BRAIN IN VIVO AFTER EXPOSURE TO ATMOSPHERES CONTAINING HIGH CONCENTRATIONS OF CO2
Authors: Miller A. L. , Hawkins R. A. , Veech R. L.
Published: October 2006

—(1) The effects of exposure of rats to increased atmospheric concentrations of CO2 on brain metabolism in vivo were studied. (2) After 2·5 min exposure to an atmosphere of 20% CO2, the rate of glucose utilization by brain decreased from 0·61 μmol/min per g to 0·32 μmol/min per g and remained between 0·3 and 0·4 μmol/min per g for 60 min, the longest interval studied. O2 utilization, calculated from the arteriovenous difference of O2 across the brain and blood flow, was 3·5 μmol/min per g in controls and was 4·7 μmol/min per g after 5 min in the 20% CO2 atmosphere. (3) The concentrations of glucose, glucose 6‐phosphate and aspartate were increased during the first 10 min of CO2 exposure whereas the concentrations of other glycolytic intermediates, tricarboxylic acid cycle intermediates and glutamate were decreased. The amount of endogenous substrate which disappeared during the first 10 min was sufficient, if used to supplement glucose as a fuel, to maintain the O2 consumption at, or slightly above, the control level. Glutamate and lactate were quantitatively the most important energy sources. (4) The mechanism whereby‘CO2 decreased the rate of glucose utilization is uncertain. The initial rise in glucose 6‐phosphate and fall in fructose 1,6‐diphosphate concentrations suggested that an inhibition of phosphofructokinase was responsible. However, after 60 min in 20% CO2, the concentrations of both of these metabolites returned to normal while the rate of glucose utilization remained depressed.
PROTEIN SYNTHESIS IN CENTRAL NERVOUS TISSUE: STUDIES ON RETINA IN VITRO1
Authors: Parks J. M. , Ames A. , Nesbett F. B.
Published: October 2006

Abstract—

Rabbit retinas were maintained in vitro in medium that resembled CSF but with leucine varied from 2 to 1000μM. Both leucine and threonine were isotopically labelled. When leucine in the medium was 100‐1000μM, leucine was incorporated into protein at 2.03 ± 0.04 (s.E.M.) μmol/g dry wt./h, a turnover per h of 0.55% of the leucine in retinal protein. Incorporation was constant for at least 7 h. It was reduced 34% when the other amino acids were omitted from the medium and 24% when they were increased 15 fold above physiological levels. When medium leucine was reduced to 2 μM with other amino acids constant, 14C‐leucine incorporation fell 70%; without significant change in 3H‐threonine incorporation, indicating a fall in intracellular specific activity of leucine. The intracellular/extracellular concentration ratio of labelled leucine was 4:1 with medium leucine 23 μM. It fell markedly when medium leucine was reduced to 2 μM or increased to 1000 μM. The concentration ratio of labelled threonine was 15:1 with medium leucine at physiological levels but fell to 6:1 when medium leucine was increased to 1000 μM. Decarboxylation removed 1.5% of free intracellular leucine per min and, at physiological concentrations, was 7.7% the rate of protein incorporation. The ratio of protein synthesis/breakdown, estimated from changes in leucine and 7 other essential amino acids in the medium, was nearly unity. The potential of this preparation for study of CNS protein metabolism is discussed.
EFFECTS OF ELECTRICAL STIMULATION OF THE NIGROSTRIATAL PATHWAY OF THE RAT ON DOPAMINE METABOLISM
Authors: Korf J. , Grasdijk L. , Westerink B. H. C.
Published: October 2006

Abstract— Electrical stimulation of the nigrostriatal dopaminergic pathway in rat brain elicited a frequency and current intensity‐dependent increased in the formation of homovanillic acid in the basal ganglia. The accumulation of the acid in probenecid‐treated animals was constant over 1 h, when maximally stimulated at 25 Hz and 300 μA. Dopamine levels remained unchanged during stimulation. When prior to stimulation the inhibitor of catecholamine synthesis α‐methyl‐p‐tyrosine methyl ester was administered, dopamine levels declined biphasically. Tyrosine and nomifensine, a dopamine uptake inhibitor, and apomorphine had no major effect on the formation of homovanillic acid, whilst α‐methyl‐p‐tyrosine prevented its formation. Our data suggest that dopamine in the striatum is compartmentalized and that the newly‐synthesized amine is released and converted to homovanillic acid. Apomorphine decreases dopamine flux only when dopaminergic neurons are at rest. When depolarized neither access of the precursor nor reuptake seem to influence the conversion of dopamine to homovanillic acid.
DHPOSITION OF LIPIDS IN THE DEVELOPING CENTRAL AND PERIPHERAL NERVOUS SYSTEMS OF THE CHICKEN
Authors: Shaikh Nisar A. , Palmer F. B. St. C.
Published: October 2006

Abstract— The lipid composition of chick brain and sciatic nerve was determined during development. It was confirmed that the addition of CaCl2 to solvents during the extraction of lipids from brain results in much higher yields of diphosphoinositides particularly from unmyelinated embryo brain. Unlike the earlier report for rat brain, the recovery of triphosphoinositides was also Substantially increased. The amount of CaCl2, required to achieve optimal recoveries decreased with increasing age and addition of more than this optimal amount depressed the yields of polyphosphoinositides, particularly triphosphoinositides. CaCl2, addition did not improve the yield of diphosphoinositides from sciatic nerve of any age but drastically reduced recovery of triphosphoinositidcs. Differenccs in the effect of CaCl2 were not the result of variation in the tissue concentrations of calcium or magnesium.

The lipid composition of sciatic nerve closely reflected that of the myelin. Both polyphosphoinositides were absent initially and their accumulation paralleled that of cerebrosides and sulfatides. The concentration of diphosphoinositides remained constant after the period of most active myelination while triphosphoinositides and the galactolipids continued to increase suggesting maturational changes in the myelin composition. The pattern of deposition in chick brain was similar except for the much greater contribution of non‐myelin structures. Both polyphosphoinositides were present in equimolar amounts in pre‐myelination embryonic tissue. The concentration of diphosphoinositides increased during active myelination only while triphosphoinositides continued to increase thereafter.
TRANSCRIPTION OF REPEATED AND UNIQUE DNA SEQUENCES IN BRAIN NUCLEI
Authors: Soga K. , Takahashi Y.
Published: October 2006

—Transcription of repeated and unique DNA in rat brain nuclei was examined using a RNA‐DNA hybridization technique. Saturation hybridization experiments with a membrane filter showed that there were differences in the base sequence complements between labelled brain and labelled liver nuclear RNA. In competition hybridization experiments using a membrane filter, brain nuclear labelled RNA was in competition most effectively with unlabelled brain nuclear RNA, but less effectively with kidney or liver nuclear RNA. Experiments using a membrane filter loaded with isolated unique or repeated DNA fragments gave similar results. Furthermore, competition hybridization with a DNA excess also showed similar results at Cot 10,000. These results indicate the existence of tissue‐specificity in the transcription of unique and repeated DNA sequences in brain nuclei. Subsequently, rat brain nuclei were separated into neuronal and glial nuclear fractions for the purpose of detecting the cell‐specificity of RNA. The results of these experiments give evidence of significant differences in the transcription of unique DNA sequences, but indicate no differences in that of repeated DNA sequences between the two nuclear classes.
UPTAKE OF NEUROTRANSMITTER CANDIDATES BY PIGEON OPTIC TECTUM
Authors: Henke H. , Schenker T. M. , Cuenod M.
Published: October 2006

—The kinetics of the uptake of various compounds into the crude mitochondrial fraction (P2‐fraction) of the pigeon optic tectum were studied. Aspartate, GABA, glutamate, glycine, proline and choline were taken up by high and low affinity systems. Only low affinity uptake was found for leucine and dopamine. The uptake for taurine was not saturable. The uptakes for all of the above compounds were temperature and sodium dependent. The high affinity system was more effected by sodium withdrawal than the low affinity system. Continuous sucrose gradients from 0.4 to 1.5 m were run with incubated P2 fractions. Particle‐bound radioactivity sedimented in a density range of 1.0 to 1.2 m‐sucrose. Additional experiments with glutamate showed that its uptake is competitively inhibited by aspartate. The addition of a 1000‐fold excess of glutamate to a P2 fraction incubated at a concentration of 10–6m‐glutamate led to a massive decrease of particle‐bound radioactivity, suggesting a coupled action of uptake and efflux.
EFFECTS OF RETINAL ABLATION ON UPTAKE OF GLUTAMATE, GLYCINE, GABA, PROLINE AND CHOLINE IN PIGEON TECTUM
Authors: Henke H. , Schenker T. M. , Cuenod M.
Published: October 2006

—The effect of retinal ablation on the high and low affinity uptake of choline, GABA, glutamate, glycine and proline into the crude mitochondrial fraction of the pigeon optic tectum was studied. After 4–8 weeks of degeneration the uptake for glutamate, and to a lesser degree the uptake for GABA, at both the high and the low affinity substrate concentration, decreased. In contrast, the uptake of glycine increased. Kinetic analysis showed that the reduced uptake of glutamate was due to a decrease in the Vmax. By intraocular injection of [3H]proline the retinal endings in the optic tectum were labelled with the fast axoplasmic transport fraction. Optic terminals labelled in this way have the same sedimentation characteristics in continous sucrose gradients as the particles accumulating giutamate in the uptake assay.
ROLE OF RIBONUCLEASE ACTION IN PHENYLALANINE‐INDUCED DISAGGREGATION OF RAT CEREBRAL POLYRIBOSOMES
Authors: Roberts S. , Morelos Beatrice S.
Published: October 2006

—l‐phenylalanine (1 mg/g body wt) or physiological saline (0.9% NaCl) was given intraperitoneally to infant (7‐day old), immature (14‐day old), and adult (42‐day old) rats. The state of ribosomal aggregation was determined in the cerebral postmitochondrial supernatant and purified polyribosome fractions prepared in the presence of rat liver ribonuclease inhibitor. Polyribosomes isolated from cerebral cortices of infant and immature rats 30 or 60 min after administration of phenylalanine were partially disaggregated, whereas the state of aggregation of polyribosomes from mature cerebrum was unchanged. In contrast, little or no evidence of phenylalanine‐induced polyribosome disruption was noted in the postmitochondrial supernatant fractions, from which the cerebral polyribosomes were prepared, in any of the animals. Omission of the ribonuclease inhibitor resulted in polyribosome disaggregation in the postmitochondrial supernatant fractions prepared from saline‐treated as well as phenylalanine‐treated infant rats, but the disruption was more profound in the latter group. Ribonuclease activities in cerebral postmitochondrial supernatant preparations from infant and immature rats were higher than the corresponding values in preparations from adult animals. In addition, the administration of phenylalanine resulted in increases in ribonuclease activities in cerebral postmitochondrial supernatant preparations from the younger animals, but had no effect on these activities in adult animals. These results suggest that alterations in structure and function of polyribosomes from the infant rat cerebrum following a loading dose of phenylalanine were related to exposure of the polyribosomes during isolation to elevated activities of cerebral ribonucleases resulting from this treatment. This hypothesis was supported by the finding that phenylalanine treatment had no effect on the incorporation in vivo of intracisternally‐administered radioactive lysine into total, soluble or ribosomal protein of infant cerebrum. However, when cerebral ribosomal RNA was differentially labelled in phenylalanine‐treated and saline‐treated infant rats by the intracisternal administration of [3H] or [14C]uridine, and polyribosome fractions were then prepared from the pooled cerebral cortices of both groups, radioactive ribosomes derived from saline‐treated rats were more highly aggregated than those derived from phenylalanine‐treated animals. It is concluded that gross alterations in cerebral polyribosome structure and function do not occur in vivo in young rats given a large amount of phenylalanine intraperitoneally. However, this treatment, in addition to increasing ribonuclease activity in cerebral cell‐free preparations, also sensitizes cerebral polyribosomes to subsequent breakdown upon exposure to ribonucleases during isolation.
THE RELEASE OF BRAIN FREE FATTY ACIDS DURING ISCHAEMIA IN ESSENTIAL FATTY ACID‐DEFICIENT RATS
Authors: Galli C. , Spagnuolo C.
Published: October 2006

—The release of free fatty acids and especially of free arachidonic acid occurring in rat brain during ischaemia has been studied in essential fatty acid‐deficient animals. Free fatty acid levels are lower in essential fatty acid‐deficient brains before and especially after 5 min of ischaemia. The percentage of arachidonic acid, in respect of total free fatty acids, is similar in both control and essential fatty acid‐deficient brains before ischaemia (0 min), but is greatly reduced in deficient brains in respect of controls after ischaemia (5 min). Total levels of free arachidonic acid are thus greatly reduced after ischaemia in the brain of essential fatty acid‐deficient rats. Focussed microwave irradiation of the brain, a technique which instantaneously kills the animals, and which was used for the determination of brain basal levels of free fatty acids and free arachidonic acid, does not per se modify brain lipid and fatty acid composition.
THE EFFECT OF HYPERTHERMIA UPON OXYGEN CONSUMPTION AND UPON ORGANIC PHOSPHATES, GLYCOLYTIC METABOLITES, CITRIC ACID CYCLE INTERMEDIATES AND ASSOCIATED AMINO ACIDS IN RAT CEREBRAL CORTEX
Authors: Carlsson C. , Hägerdal M. , Siesjö B. K.
Published: October 2006

Abstract—

The influence of hyperthermia on cerebral blood flow, cerebral metabolic rate for oxygen and cerebral metabolite levels was studied by increasing body temperature from 37° to 40°C and 42°C in rats under nitrous oxide anaesthesia maintained at constant arterial CO2 tension. The metabolic rate for oxygen increased by 5‐6% per degree centigrade. At 42°C the increase in cerebral blood Row was comparable to that in the metabolic rate. The increased temperatures were not accompanied by changes in organic phosphates (phosphocreatine, ATP, ADP or AMP) or in lactate/pyruvate ratio. There was an increase in the tissue to blood glucose concentration ratio. At steady state, there was an increase in glucose‐6‐phosphate but no other changes in glycolytic metabolites or citric acid cycle intermediates, and the only change in amino acids studied (glutamate, glutamine, aspartate, alanine and GABA) was an increase in glutamate concentration.
STABILITY OF ENZYMES IN POST‐MORTEM RAT BRAIN1
Authors: Fahn S. , Côté L. J.
Published: October 2006

Abstract—

Enzyme activities were measured in rat brains kept at room temperature for various intervals after death by decapitation. Tytosine hydroxylase, monoamine oxidase, choline acetyltransferase, and acetylcholinesterase show a substantial decline in activity over 14h reaching 64, 78, 60 and 58%, respectively. of the zero‐time activity. DOPA decarboxylase, glutamic acid decarboxylase, lactate dehydrogenase, Na‐K‐ATPase and Mg‐ATPase show less than a 15% decline in activity. The activities of most of the enzymes studied show little change time period when human brain specimens are likely between the 6th and 14th hour after death, the to be obtained for biochemical studies
POST‐ISCHEMIC CHANGES IN CERTAIN METABOLITES FOLLOWING PROLONGED ISCHEMIA IN THE GERBIL CEREBRAL CORTEX
Authors: Mrsulja B. B. , Lust W. D. , Mrsulja B. J. , Passonneau J. V. , Klatzo I.
Published: October 2006

‐Eight metabolites were measured in the post‐ischemic period following either 1 or 3 h of unilateral ischemia in the gerbil cerebral cortex. The levels of ATP, P‐creatine, glucose, glycogen and GABA were essentially restored by 1 h after ischemia. In the 3 h ischemic animals. glycogen continued to increase to greater than control values aftcr 5 and 20 h of recirculation. The Icvels of glutamate were unchanged during the ischemic episode, but decreased to 60% of control at Smin and 1 h after either period of ischemia. The concentrations of cyclic AMP, which were 4‐to 5‐fold elevated during ischemia. increased an additional 6‐fold 5 min after recirculation in both groups. Arter 1 h of recovery. the levels were not different from control values. After the 1 h ischemic period, lactate levels recovered between 5 and 20 h of recirculation. In the 3 h ischemic animals. lactate concentrations were still elevated even after 20 h of recirculation. These data suggest that with the exception of lactate. recovery of metabolites is not sevcrely compromiscd by either 1 or 3 h of ischemia. Furthermore, the changes in glycogen. glutamate and cyclic AMP after recirculation suggest that the recovery process is not just a rcversal of the changes observed during ischemia.
THE EFFECTS OF PHENYLALANINE ON AMINO ACID METABOLISM AND PROTEIN SYNTHESIS IN BRAIN CELLS IN VITRO1
Authors: Hughes J. V. , Johnson T. C.
Published: October 2006

Incubation of brain cell suspensions with 14 mM‐phenylalanine resulted in rapid alterations of amino acid metabolism and protein synthesis. Both thc rate of uptake and the final intracellular concentration of several radioactively‐labelled amino acids were decreased by high concentrations oi phenylalanine. By prelabelling cells with radioactive amino acids, phenylalanine was also shown to effect a rapid loss of the labelled amino acids from brain cells. Amino acid analysis after the incubation of the cells with phenylalanine indicated that several amino acids were decreased in their intracellular concentrations with effects similar to those measured with radioisotopic experiments (large neutral > small and large basic > small neutral > acidic amino acids). Although amino acid uptake and efflux were altered by the presence of 14 mwphenylalanine, little or no alteration was detected in the resulting specific activity of the intracellular amino acids. High levels of phenylalanine did not significantly altcr cellular catabolism of either alanine, lysine, leucine or isoleucine. As determined by the isolation of labcllcd aminoacyl‐tRNA from cells incubated with and without phenylalanine, there was little or no alteration in the level of this precursor for radioactive alanine and lysine. There was, however, a detectable decrease in thc labelling of aminoacyl‐tRNA for leucine and isoleucine. Only aftcr correcting for the changes of the specific activity of the precursors and thcir availability to translational events, could the effects of phenylalanine on protein synthesis be established. An inhibition of the incorporation into protein for each amino acid was approximately 20%.
SELECTIVE LOCALIZATION OF A HIGH AFFINITY CHOLINE UPTAKE SYSTEM AND ITS ROLE IN ACh FORMATTON IN CHOLINERGIC NERVE TERMINALS
Authors: Suszkiw J. B. , Pilar G.
Published: October 2006

The avian iris‐ciliary nerve preparation exhibits two distinct choline uptake systems. One component, a sodium dependent, high affinity system Km‐2 am and Vmax ‐ 0.5 pmolpin per preparation is confined to nerve terminals. The other component is localized in muscle cells. It is sodium independent and low affinity system (Km ‐ 200 am and Vmax ‐ 16 pmol/min per muscle). The high affinity uptake of choline and the synthesis of ACh in the nerve terminals are coupled. Vmax Ach formation ‐0.5 pmol/min. is the same as Vmax for choline transport; however. with the external choline concentration equal to that of avian plasma only ‐50% of choline taken up is converted to ACh. In contrast to the nerve terminals, the cell bodies of the same neurons are deficient in the high affinity uptake‐ACh synthesis coupled system. This indicates a nerve terminal membrane specialization related to neuro‐transmitter synthesis.
PURIFICATION OF NERVE GROWTH FACTOR ANTIBODIES BY AFFINITY CHROMATOGRAPHY
Authors: Stoeckel K. , Gagnon C. , Guroff G. , Thoenen H.
Published: October 2006

Pure antibodies to nerve growth factor have been isolated from sheep nerve growth factorantiserum by affinity chromatography using 2.5 S nerve growth factor linked to Sepharose 4B by means of cyanogen bromide. The elution of the antibodies was accomplished either at low pH (pH 2) or by high salt concentration (4.5 wMgC12). The purity of the antibodies was established by SDS‐gel electrophoresis. Their immunological activity was tested by imrnunoprecipitation and their biological activity in a tissue culture assay using embryonic chick dorsal root ganglia.
DEVELOPMENT AND REGULATION OF LIPID SYNTHESIS FROM KETONE BODIES BY RAT BRAIN
Authors: Patel M. S. , Owen O. E.
Published: October 2006

Abstract—

Cerebral cortex slices from 1‐day old rats incorporated actively 3‐hydroxy[3‐14C] butyrate into lipids. The rate of synthesis increased moderately during the first postnatal week and then decreased rapidly reaching negligible rates by the end of the fourth postnatal week. The incorporation of [3‐14C]acetoacetate (5 mM) and 3‐hydroxy[3‐14C]butyrate (5 mM) at non‐physiological concentrations into lipids by cerebral cortex from 1‐week old rats was markedly stimulated in the presence of added glucose; however, the addition of glucose had no effect on the oxidation of ketone bodies to 14CO2 At physiological concentrations of acetoacetate (0.5 mM) and 3‐hydroxybutyrate (1 mM), glucose stimulated both the oxidation of ketone bodies to 14CO2 and the incorporation of ketone body‐carbon into cerebral lipids. In contrast, the oxidation of [U‐14C]glucose to CO2 and its incorporation into lipids by brain slices were markedly reduced in the presence of ketone bodies at physiological as well as non‐physiological concentrations. However, the total rate of lipid synthesis, as determined by the incorporation of 3H from 3H2O, was maintained under these conditions. This indicated that the decreased contribution of the acetyl moiety from glucose was compensated to a similar extent by acetyl‐CoA formed from ketone bodies. The findings show that both acetoacetate and 3‐hydroxybutyrate are better precursors than glucose for in vitros lipid synthesis in developing rat brain.
THE DISTRIBUTION OF GLYCINE, GABA, GLUTAMATE AND ASPARTATE IN RABBIT SPINAL CORD, CEREBELLUM AND HIPPOCAMPUS
Authors: Berger Sosamma J. , Carter Joyce G. , Lowry O. H.
Published: October 2006

Abstract—

The distribution of glycine, GABA, glutamate and aspartate was measured among about 60 subdivisions of rabbit spinal cord, and among the discrete layers of cerebellum, hippocampus and area dentata. A more detailed mapping for GABA was made within the tip of the dorsal horn of the spinal cord. Spinal ventral horn and dorsal root ganglion cell bodies were analyzed for the amino acids and for total lipid. The distribution of lipid and lipid‐free dry weight per unit volume was also determined in spinal cord. Calculated on the basis of tissue water, glycine in the cord is highest in lateral and ventral white matter immediately adjacent to the ventral grey. The distribution of GABA is almost the inverse of that of glycine with highest level in the tip of dorsal horn. It is most highly concentrated in the central 75% of Rexed layers III and IV. Aspartate in the tip of ventral horn is 4‐fold higher than in the tip of the dorsal horn and 3 times the average concentration in brain. Glutamate was much more evenly distributed and is relatively low in concentration with slightly higher levels in dorsal than in ventral grey matter. Large cell bodies in both ventral horn and dorsal root ganglion contained high levels of glycine. As reported by others, GABA was found to be high in cerebellar grey layers, area dentata, and regio inferior of hippocampus. Glycine was moderately high in cerebellar layers but moderate to low in hippocampus and area dentata.
ARGINASES OF MOUSE BRAIN AND LIVER
Authors: STEWART J. A. , CARON H.
Published: October 2006

The arginase present in mouse brain and liver was studied in order to determine if the activity in both tissues was due to the same enzyme. Mouse liver contains only one arginase enzyme whereas mouse brain contains two. One of the arginases in the brain is distinct from the liver enzyme as determined by fractionation on DEAE‐cellulose, CM‐cellulose and disc gel electrophoresis. The second enzyme from brain tissue has the same properties as the liver enzyme when subjected to these same fractionation techniques. However this arginase can be distinguished from the liver enzyme by its Km for arginine heat lability and MnCl2 activation curve. Thus both arginases in brain differ from the liver enzyme.

No interconversion of the brain enzymes was detected, and the molecular weight of all the arginases appears to be the same. The observation of multiple distinct brain and liver arginases in mouse brain and liver was confirmed with bovine tissues.
KINETICS OF IN VIVO CONVERSION OF γ‐[3H]AMINOBUTYRIC ACID TO γ‐[3H]HYDROXYBUTYRIC ACID BY RAT BRAIN1,2
Authors: Gold B. I. , Roth R. H.
Published: October 2006

Abstract— The appearance of γ‐[3H]hydroxybutyric acid ([3H]GHB) in rat brain at various times after the intraventricular administration of [3H]GABA was determined. Radioactivity recovered as [3H]GHB was maximal 30 s after [3H]GABA administration and declined exponentially thereafter. From a linear transformation of the disappearance with time of [3H]GHB formed from [3H]GABA, the fractional rate of disappearance and turnover time of GHB were calculated. Administration of amino‐oxyacetic acid (50 mg/kg i.p.) 1 h before [3H]GABA, reduced [3H]GHB formation, measured 4 min after [3H]GABA, to 28% of that found in control animals. This strongly suggests that GABA‐transaminase catalyzes at least one step in the conversion pathway. [3H]GHB recoverable 4 min after [3H]GABA was unchanged when animals were pretreated with pyrazole (1.25–5.0 mmol/kg), diphenyl‐hydantoin (25 and 75 mg/kg), phenobarbital (7.5–60 mg/kg), ethanol (1.25–5.0 g/kg), or morphine (2.5–10 mg/kg). Significantly more [3H]GHB could be recovered at several time points from animals which had been pretreated with 50 mg/kg i.p. of the convulsant 3‐mercaptopropionic acid.
INTERACTION OF TAURINE, GABA AND GLUTAMIC ACID WITH SYNAPTIC MEMBRANES
Authors: Lähdesmäki P. , Kumpulainen E. , Raasakka O. , Kyrki P.
Published: October 2006

Abstract— Sodium‐independent but calcium‐dependent binding of taurine, GABA and glutamate to synaptic membranes from calf brain cortex is demonstrated. Binding constants of 1.5 μm for taurine, 46 μm for GABA and 45 μm for glutamate were obtained, being largely mixed with transport constants derived from the influx to empty membrane‐pouches (particularly in the case of GABA and glutamate), and in the case of GABA also with the non‐specific binding. Certain structural analogues of amino acids inhibited the binding, aspartate being the most potent inhibitor for glutamate, and β‐alanine for GABA and taurine, but KCN and 2,4‐dinitrophenol had no effect. The membrane‐attached [35S]taurine was divided by differential elution into easily extractable and firmly bound components.
NET UPTAKE OF L‐GLUTAMATE AND GABA BY HIGH AFFINITY SYNAPTOSOMAL TRANSPORT SYSTEMS
Authors: Roskoski Robert
Published: October 2006

Abstract— Reuptake of neuroactive amino acids by high affinity transport systems in the CNS is thought to terminate the neurotransmitter activity of these substances. This notion has been challenged since the homoexchange of synaptosomal and exogenous L‐glutamate and the corresponding homoexchange of synaptosomal and exogenous GABA has been demonstrated. We reported that depolarizing media (56 mM‐KCl, 1 mM‐CaCl2) lowers the GABA content of synaptosomes. In such synaptosomes, net and apparent (radioactive) GABA uptake are similar. When rat cortical synaptosomes (1 mg protein/ml) are incubated with 10μM‐[14C] L‐glutamate, net and apparent (radioactive) uptake are similar. When the synaptosome levels are decreased to 0.5 mg protein/ml or less, then net uptake becomes a fraction of radioactive uptake (exchange ensues). Net L‐glutamate uptake is Na +‐dependent and temperature‐dependent. Furthermore, a 1 mM concentration of KCl or RbCl supports net L‐glutamate and GABA uptake. LiCl, NH4Cl, CsCl and choline chloride are ineffective. In addition, diaminobutyric acid (but not β‐alanine) inhibits net and apparent GABA uptake. The demonstration of net uptake of L‐glutamate and GABA by their respective high affinity systems is consonant with the idea that these systems may play a role in neurotransmitter inactivation in the synaptic region.
ALTERATIONS IN RECEPTORS CONTROLLING DOPAMINE SYNTHESIS AFTER CHRONIC ETHANOL INGESTION
Authors: Tabakoff Boris , Hoffman Paula L.
Published: October 2006

The influence of acute and chronic ethanol treatment and withdrawal on regulation of dopamine synthesis in striatal and mesolimbic areas of mouse brain was evaluated. Tyrosine hydroxylase activity was estimated by measuring in vivo DOPA accumulation after inhibition of aromatic amino acid decarboxylase. Eight hours after a single (3 g/kg) dose of ethanol, DOPA synthesis was increased and pimozide, a dopamine receptor antagonist, stimulated DOPA synthesis to the same degree in ethanol‐treated and control animals. On the other hand, 8 h after withdrawal of animals from chronic ethanol treatment, endogenous dopamine synthesis was the same in ethanol‐withdrawn and control animals, but the stimulation of dopamine synthesis produced by low doses of pimozide or haloperidol was significantly less in the animals that had consumed ethanol. This effect was even more apparent at 24h after withdrawal; by 3 days after withdrawal the decreased response of ethanol‐withdrawn animals to the administration of dopamine receptor blockers was no longer statistically significant. At all time points tested, high doses of pimozide or haloperidol stimulated DOPA synthesis equally in control and ethanol‐withdrawn animals. Chronic ethanol treatment and withdrawal may alter the coupling between dopamine receptors which regulate dopamine synthesis and tyrosine hydroxylase.
Energy flux and lactate production in rat cerebral cortex during the first 5‐10 s of bicuculline‐induced seizures
Authors: Folbergrova J. , Nilsson B. , Nordström C.‐H. , Siesjö B. K.
Published: October 2006

Neurochemical studies of induced seizures have provided much information on metabolic capacity in the brain. However, there is no general agreement on the magnitude of changes in cerebral metabolic rate. Presumably, differences in results depend both on the models of epilepsy used and on methodological factors.
ALTERATIONS IN GABA METABOLISM AND MET‐ENKEPHALIN CONTENT IN RAT BRAIN FOLLOWING REPEATED ELECTROCONVULSIVE SHOCKS
Authors: Green A. R. , Peralta E. , Hong J. S. , Mao C. C. , Atterwall C. K. , Costa E.
Published: October 2006

The effects of electroconvulsive shock (ECS; 120 V for 1 s through ear‐clip electrodes) or sub‐convulsive shocks (70 V for 1 s) on rat brain GABA and met‐enkephalin concentration and GABA turnover has been examined 24 h after a single treatment (×1) or once daily for 10 days (×10). ECS × 10 increased GABA concentrations in the N. caudatus and N. accumbens and decreased the synthesis rate of GABA by 40% and 50% respectively in these regions. Sub‐convulsive shocks (× 10 × 10) or ECS × 1 had no effect. No consistent changes were seen in the substantia nigra. Met‐enkephalin concentrations increased by 50% in the N. caudatus after ECS × 10 but were unchanged in the cortex and pons/medulla. No other shock regimen had any effect on the concentration of this peptide. The results are discussed in relation to the enhanced monoamine‐induced responses seen only after ECS × 10.
FUNCTIONAL PROPERTIES OF NEURONAL AND GLIAL ISOENZYMES OF BRAIN ENOLASE
Authors: Marangos P. J. , Parma A. M. , Goodwin F. K.
Published: October 2006

Abstract—

Two of the major brain enolase (EC 4.2.1.11) isoenzymes exist as cell specific forms. The neuron specific enolase (NSE) is localized in neurons and the non‐neuronal enolase (NNE) in glial cells. A third enolase containing one subunit from each of the above species is also present in brain and has been designated hybrid enolase. The stabilities of the brain enolases towards incubation with chloride and bromide salts is markedly different. NNE is rapidly inactivated upon incubation in 0.5 M‐KCI or KBr while NSE is minimally effected and the hybrid has an intermediate stability. The inactivation is temperature dependent and reversible by salt removal. Magnesium exerts a stabilizing effect on each enzyme form. The mechanism of the reversible salt inactivation involves dissociation of the enolase subunits with reassociation occurring during reactivation.

The brain enolases also display marked stability differences during incubation in 3 M‐urea. with the neuronal form again being more stable. The urea inactivation was highly reversible for NNE but only marginally so for NSE. The neuronal enolase is also by far the most stable of the brain enolases at 50°C.
EARLY POSTNATAL STARVATION CAUSES LASTING BRAIN HYPOMYELINATION
Authors: Wiggins Richard C. , Fuller Gregory N.
Published: October 2006

Abstract— Rats were starved during various intervals of postnatal development, and subsequently, they were rehabilitated by feeding ad lib. through 60 days of age. Starvation was induced by an increasingly severe regime of maternal deprivation that results in a 50% deficit in body weight at 20 days. Relatively mild and brief starvation, from birth through 8 days, as well as more severe starvation occurring late, from 14 to 30 days, produced no lasting deficit in myelin accumulation. Starvation from birth through 14 days or from birth through 20 days produced lasting, significant myelin deficits in all regions (cerebrum, cerebellum, medulla, midbrain, hippocampus, hypothalamus, and striatum) of the brain. These data, in combination with our previous metabolic studies of myelin synthesis of starved and control rats, show that starvation early in development, during the period of oligodendroglial cell multiplication, accounts for an immediate reduction in myelin synthesis, and that the consequent myelin deficit proves irreversible in subsequent nutritional rehabilitation. In contrast, brain weight is subject to substantial growth catch‐up upon rehabilitation. Where the onset of starvation was late, during the period of rapid myelin synthesis, but after completion of the major period of oligodendroglial cell proliferation, no lasting myelin deficit was observed upon rehabilitation.
IN VITRO FORMATION OF POLYUNSATURATED FATTY ACIDS BY DESATURATION IN RAT BRAIN: SOME PROPERTIES OF THE ENZYMES IN DEVELOPING BRAIN AND COMPARISONS WITH LIVER1
Authors: Cook H. W.
Published: October 2006

Abstract— In vitro desaturation of [1‐C14]linolenic, linoleic, oleic, and icosatrienoic acids was determined using homogenates and subcellular fractions of developing rat brain and liver. Linolenic, linoleic, and oleic acids were desaturated in the δ6‐position and activity was optimal in the presence of CoA, ATP, MgCl2, and NADH in a citrate‐phosphate buffer at pH 6.0. Icosatrienoic acid was desaturated in the δ5‐position with a much broader pH optimum. The unstable desaturation systems of brain were protected by reduced glutathione and niacinamide and markedly inhibited by dithiothreitol, p‐chloromercuribenzoate, sodium cyanide or bathophenanthroline sulfonate. With brain homogenate of neonatal rats, the relative rates of desaturation of these substrates were 18:3(n ‐ 3) > 18:2(n ‐ 6) > 20:3(n ‐ 6) > 18:l (n ‐ 9). Specific activity of brain enzymes was greatest in neonatal rats with fluctuations in activity between 3 and 6 days of age. During this period, liver enzyme appeared to alter in a reciprocal manner. Total desaturation capacity of brain was maximal and fairly constant between 4 and 20 days of age, whereas liver activity increased dramatically after weaning. The activity of crude microsomal preparations from neonatal brain, like that of liver microsomes, was stimulated by a heat‐labile component of the cytosolic fraction. These results demonstrate that brain has a high capacity for desaturation of the essential fatty acids during crucial stages of brain development when liver activity is relatively low.
STRUCTURE‐ACTIVITY STUDIES ON THE INHIBITION OF GABA BINDING TO RAT BRAIN MEMBRANES BY MUSCIMOL AND RELATED COMPOUNDS
Authors: Krogsgaard‐Larsen P. , Johnston G. A. R.
Published: October 2006

Abstract— A series of compounds structurally related to muscimol (5‐aminomethyl‐3‐isoxazolol) was tested as inhibitors of the sodium‐independent binding of GABA to membranes from rat brain. Muscimol, 5‐(l‐aminoethyl)‐3‐isoxazolol, 5‐(2‐aminoethyl)‐3‐isoxazolol (homomuscimol), and the bicyclic derivative 4,5,6,7‐tetrahydroisoxazolo[5,4‐c]pyridin‐3‐ol (THIP) were relatively potent inhibitors of GABA binding. THIP is an analogue of muscimol locked in a folded conformation. The structurally related compound 1,2,3,6‐tetrahydropyridine‐4‐carboxylic acid (isoguvacine), a semirigid analogue of trans‐4‐aminocrotonic acid, was also a potent inhibitor of GABA binding. Apart from muscimol, these inhibitors of GABA binding did not influence the sodium‐dependent,‘high‐affinity’ uptake of GABA in rat brain slices, whereas the potent GABA uptake inhibitors guvacine and nipecotic acid did not influence GABA binding. The present results support previous findings that different conformational modes of GABA interact with GABA postsynaptic receptors and the neuronal GABA transport system in rat brain, and indicate that the ‘active conformation’ of GABA with respect to the receptors is partially folded and almost planar. Based on a comparison of the present results with previous in vivo studies the structural requirements for GABA‐like activity in rat cerebral cortex and cat spinal cord seem to be somewhat different.
DEVELOPMENT OF A SPECIFIC RADIOIMMUNOASSAY FOR ACETYLCHOLINE
Authors: Spector S. , Feux A. , Semenuk G. , Finberg J. P. M.
Published: October 2006

Abstract— The synthesis of an acetylcholine‐like immunogen and its use in production of antibodies specific to ACh is described. Cross‐reactivity of anti‐ACh antibody to choline was only 0.1% that to ACh. Insignificant cross reaction to acetate and phosphorylcholine occurred, enabling use of these antibodies in a radioimmunoassay for determination of endogenous ACh levels. Significant cross‐reactivity of the antibody to succinylcholine. decamethonium, dimethylphenylpiperazinium, carbachol and butyr‐ylcholine was observed. The correlation coefficient for determination of endogenous ACh by bioassay and radioimmunoassay was 0.994. ACh levels by radioimmunoassay in brain areas of rats killed by microwave irradiation were: striatum, 77.8; cortex, 28.8; hippocampus, 25.4; midbrain. 47; and hypothalamus, 25 nmol/g.
PSYCHOLOGICAL STRESS REDUCES CYCLIC 3′,5′‐ADENOSINE MONOPHOSPHATE LEVELS IN THE CEREBRAL CORTEX OF CONSCIOUS RATS, AS DETERMINED BY A NEW CRYOGENIC METHOD OF RAPID TISSUE FIXATION1
Authors: Skinner James E. , Welch K. M. A. , Reed Jane C. , Nell Janet H.
Published: October 2006

Abstract— Cryoplates were implanted on the surface of the cortex in 32 chronic rat preparations. These devices were used both to freeze and to extract small samples of tissue. Coolant was circulated through each device by small flexible polyethylene tubes. Two series of experiments were performed. In the first, the animals were unrestrained and showed no behavioral signs of stress during the freeze fixation. The temperature responses of the cryoplates were very rapid (−632°C/s), and samples more than 1 mm thick were frozen and extracted within a few hundred ms following the onset of cooling. Each sample was analyzed for 3′.5′‐adenosine monophosphate (cyclic AMP) and protein content. The results from the cryoplate group (25.6 ± 15.6pmol cyclic AMP/mg protein) were compared to those obtained from two other groups in which freeze fixation was produced by immersion in liquid nitrogen (13.6 ± 4.6pmol/mg protein) or decapitation into liquid nitrogen (18.6 + 7.6pmol/mg protein). In the second series of experiments, three types of stress (limb restraint, non‐adaptation to the experimental situation, and moderate cutaneous electric shock) were induced separately in order to determine the influence of each on cortical levels of cyclic AMP. Control animals were highly adapted to the experimental situation, freely moving and not shocked. The samples from each of the stressed groups showed a statistically significant (P≤. 0.01) reduction in cyclic AMP in comparison with the level in the controls (control: 29.3 pmol/mg protein; restrained: 14.2pmol/mg protein; unadapted: 9.6pmol/mg protein; shocked: 7.1 pmol/mg protein). Thus, psychological and physical stress reduced cyclic AMP content in parietal cortex.

Results from the second series of experiments suggest that the significantly higher mean and larger standard deviation of the cryoplate group in the first series are due to less psychological and physical stress being evoked by our method; different types of stress appear to account for the two different lower levels found in the immersion and decapitation groups. We believe that our method of cryogenic tissue fixation offers an improved approach to study of the neurochemical correlates of behavioral and neuroelectric events in the conscious animal.
EFFECT OF TRANSIENT ISCHEMIA ON MONOAMINE LEVELS IN THE CEREBRAL CORTEX OF GERBILS1,2
Authors: Gaudet Robert , Welch K. M. A. , Chabi Eva , Wang Tseng‐Pu
Published: October 2006

Abstract— Cortical monoamine changes during ischemic episodes of varied duration and their sequence of changes following cerebral reperfusion were studied in the gerbil. Forty‐one percent of 280 animals exhibited signs of cerebral hemispheric ischemia (stroke) after unilateral common carotid artery occlusion. Norepinephrine (NE) levels decreased after 60 min in the occluded hemisphere of stroked animals but dopamine (DA) levels were unaltered. S‐Hydroxytryptamine (5‐HT) levels became bilaterally reduced in both stroked and non‐stroked animals as soon as S min after occlusion.

Upon reperfusion after periods of 30 or 60 min of occlusion there was a bilateral rebound increase of cortical NE and DA levels to well above control values in stroked and non‐stroked animals. 5‐HT levels remained reduced in both groups.

Results suggest disorder of monoamine metabolism in ischemic brain which persists during the early reperfusion period, perhaps contributing to deficits in neurological function.

Monoamine changes in contralateral non‐ischemic hemispheres both during the occlusion and reperfusion periods are thought further evidence of diaschisis.