bluuebunny/crossref_metadata_2025 huggingface dataset:
AXOPLASMIC TRANSPORT OF CHOLINE ACETYLTRANSFERASE ACTIVITY IN MICE: EFFECT OF AGE AND NEUROTOMY
Authors: Jablecki C. , Brimijoin S.
Published: October 2006

—We studied the axoplasmic transport of choline acetyltransferase (CAT) activity in sciatic nerves of normal mice of various ages. For at least 3 days after unilateral ligation of sciatic nerves of 6 and 30‐week‐old mice, the CAT activity in the ligated nerve increased as a linear function of time and the increase was confined to the 3 mm length of nerve immediately proximal to the ligature. The rate of increase of CAT activity in the ligated nerves of the 30‐week‐old mice was only 45 ± 6% that of the 6‐week‐old mice, whereas the CAT activity of non‐ligated sciatic nerves of the older mice was 87 ± 6% more than that of the younger mice (n = 18, P < 0·001). The average velocity of axoplasmic transport of CAT activity was five times greater in the younger mice (1·5 ± 0·2 mm/day vs 0·3 ± 0·1 mm/day, n = 6, P < 0·01). Even greater differences were observed between still younger and older animals: the av velocity of axoplasmic transport of 2‐week‐old mice (3·5 ± 0·2 mm/day) was 17·5 times greater than that of 36‐week‐old mice (0·2 ± 0·1 mm/day). We also studied the axoplasmic transport of CAT activity in 6‐week‐old mice after unilateral section of the sciatic nerve. For at least 3 months after the operation, there were no differences between the sectioned nerves and the intact contralateral nerves with respect to the increase in CAT activity immediately proximal to a ligature placed at various times after neurotomy and one day before sacrifice. On the other hand, there was a reduction in the CAT activity of more proximal segments of the sectioned nerves. The reduction of CAT activity was maximal (52 ± 3%) 3 weeks after the operation when the maximum increase (2·5‐fold) in the av velocity of axoplasmic transport of CAT activity was recorded (n = 6, P < 0·001). The inclusion of purified (100‐fold) mouse brain CAT activity in the assays for the CAT activity of nerve segments demonstrated that the differences in content and rate of transport were not due to the presence of activators or inhibitors of CAT activity. These differences probably reflect physiologic changes in the axoplasmic transport of cholinergic neurons during development and regeneration.
LONG‐TERM EFFECTS OF TEFLUTIXOL ON THE SYNTHESIS AND ENDOGENOUS LEVELS OF MOUSE BRAIN CATECHOLAMINES
Authors: Hyttel J.
Published: October 2006

—The long term effects on accumulation of 14C‐labelled dopamine and noradrenaline after [14C]tyrosine administration and on the endogenous levels of catecholamines in mouse brain were studied after treatment with a new potent thioxanthene neuroleptic, teflutixol. The drug was given as a single dose (5 mg/kg i.p.), as repeated daily doses (1·25 mg/kg p.o.), or as a single dose of the palmitic ester in Viscoleo® (20 mg/kg s.c). After a single dose, teflutixol increased catecholamine synthesis (100%). Noradrenaline synthesis rapidly returned to normal, whereas decreased dopamine synthesis was seen from the third to sixth day, after which it was normal. When the receptors were continuously exposed to teflutixol, either by daily dosage or by the depot preparation, catecholamine synthesis was increased for the first few days but then returned to normal, indicating development of tolerance. Endogenous concentrations of catecholamines were only decreased during the first few days, when the increase in synthesis was greatest. The findings are in accordance with results obtained by Møller Nielsen & Christensen (1975), who found that receptor blockade was followed by receptor supersensitivity after treatment with a neuroleptic compound. The receptor blockade may activate a feedback mechanism that induces increased nervous firing with increased amine synthesis as a consequence. The resulting supersensitivity, if sufficiently great, may lead to reduced nervous firing, followed by slowing of dopamine synthesis.
THE EXCHANGE OF PHOSPHATIDYLCHOLINE AND OF PHOSPHATIDYLINOSITOL IN SHEEP BRAIN
Authors: Brammer M. J. , Sheltawy A.
Published: October 2006

—The exchange of phospholipids between liposomes and brain mitochondria has been studied in the presence of pH 5·1 supernatant fluids derived from rat, guinea pig, sheep and ox brains. The exchange phenomenon was similar to that observed in liver and heart, but phosphatidylinositol and not phosphatidylcholine was the most rapidly exchanging phospholipid. The phosphatidylcholine exchange activity was purified 186‐fold from sheep brain and the protein fraction contained two major and several minor protein species. The phosphatidylcholine and phosphatidylinositol exchange activities have been shown to have very similar molecular weights and isoelectric points. However, their behaviour in response to changes in liposomal surface charge suggested that separate proteins might be involved in stimulating the exchange of the two phospholipid classes.
ORGANIC MERCURIAL ENCEPHALOPATHY: IN VIVO AND IN VITRO EFFECTS OF METHYL MERCURY ON SYNAPTOSOMAL RESPIRATION
Authors: Verity M. A. , Brown W. Jann , Cheung M.
Published: October 2006

—A reproducible model of subacute methyl mercury (MeHg) intoxication was developed in the adult rat following the daily intragastric administration of 10 mg methyl mercury/kg body wt. Synaptosomes isolated from animals during the latent phase of mercury neurotoxicity (6‐10 days) demonstrated no significant change in respiratory control, State 3, State 4, or 2,4‐dinitrophenol stimulated respiration with succinate, glutamate or pyruvate plus malate. During the neurotoxic phase, a significant decline in respiratory control was evident with all substrates. Cerebellar synaptosomes revealed qualitatively similar but quantitatively greater inhibition of 2,4‐dinitrophenol stimulated respiration during the latent and neurotoxic phases with glutamate.

In vitro studies of synaptosome respiration, oxidative phosphorylation and respiratory control with 5‐15 μm‐methyl mercury revealed a stimulation of initial State 4 respiration, loss of RCI, inhibition of State 3 but no change in the gramicidin or 2,4‐dinitrophenol uncoupled rate supported by pyruvate‐malate. Phosphate did not relieve the State 3 inhibition. At 25 μm‐methyl mercury and above, considerable inhibition of electron transfer occurred. At this concentration, cytochrome c oxidase was inhibited 50%. Isosmotic replacement of medium KC1 by mannitol reduced the MeHg stimulation of State 4 respiration but had no effect on MeHg inhibition of ADP stimulated respiration. Half‐maximal stimulation of State 4 respiration by MeHg occurred at [K]+⋍ 6 mm. These findings are compatible with an energy‐linked methyl mercury induced cation translocation across the synaptosome (mitochondrial) membrane.
THE REACTION OF CHOLINE AND 3,3‐DIMETHYL‐1‐BUTANOL WITH THE ACETYLENZYME FROM ACETYLCHOLINESTERASE
Authors: Dawson R. M.
Published: October 2006

—A comparison was made of the manner in which choline chloride and 3,3‐dimethyl‐1‐butanol react with the acetylenzyme formed during the hydrolysis of esters of acetic acid by acetylcholinesterase. Acetylcholine and acetylthiocholine were the substrates. The ratio of the formation of alkyl acetate to that of acetic acid increased linearly with the concentration of dimethylbutanol, but approached a limiting value as the concentration of choline was increased. Total enzymic activity was inhibited by choline and activated slightly by dimethylbutanol. The effects of varying ionic strength, pH and substrate concentration were examined. The effects of tetraethyl‐ and tetramethylammonium ions on the reaction of dimethylbutanol with the acetylenzyme were also studied. The results suggest that dimethylbutanol and choline bind to different regions of the active site. A mechanism for the reaction of choline and substrate with acetylcholinesterase is suggested.
SEQUENTIAL ANALYSIS: MANGANESE, CATECHOLAMINES AND l‐DOPA INDUCED DYSKINESIA
Authors: Papavasiliou P. S. , Miller S. T. , Cotzias G. C. , Kraner H. W. , Hsieh R. S.
Published: October 2006

Abstract— This paper specifies methodology for the sequential determination of manganese and catecholamines in selfsame brain samples and shows correlations between them. Small samples were obtained from five regions of brain of cats that had received either saline or levodopa. The doses of levodopa were varied so that although all animals reacted, some developed dyskinesia while others did not. Each sample was first analyzed nondestructively for manganese and then destructively for dopa and dopamine; thus errors inherent in analysing separate samples, due to the structural heterogeneity of the brain, were avoided. Statistically significant correlations were found (1) between levodopa‐induced dyskinesia and the concentrations of dopamine and manganese in some of the regions analysed, and (2) between the concentrations of dopamine and of manganese in the caudates of the cats receiving the highest doses of levodopa.
CHANGES IN GLYCOGEN PHOSPHORYLASE ACTIVITY AND GLYCOGEN LEVELS OF MOUSE CEREBRAL CORTEX DURING CONVULSIONS INDUCED BY HOMOCYSTEINE
Authors: Folbergrová J.
Published: October 2006

Abstract—

Glycogen phosphorylase activity and glycogen levels were investigated in the cerebral cortex of mice of two different strains under the influence of homocysteine. Control levels of glycogen and total phosphorylase activity (i. e. activity in the presence of 1 mM‐AMP) were higher in the inbred strain A, whereas a higher proportion of phosphorylase in its active form (activity without 5′‐AMP) was obtained in the ICR strain (probably due to slower fixation of brain in this strain). Changes occurring after the administration of homocysteine were similar in both strains. With the onset of first clonic seizures a marked increase of phosphorylase a occurred (increase 99 per cent in strain A and 46.5 per cent in ICR, respectively). During the latter phase of tonic seizures active phosphorylase a did not significantly differ from control values. Five minutes after the end of a tonic seizure, i. e. when partial recovery could already be observed, a marked decrease of active phosphorylase a in comparison with control values, was evident (decrease against control values of 45.5 per cent in strain A and 30.5 per cent in ICR, respectively). The total phosphorylase activity was not affected in strain A, whereas a slight increase during clonic seizures was seen in the ICR strain. In accordance with the enhanced activation of phosphorylase at the onset of clonic seizures, a marked decrease in glycogen levels (35‐50 per cent) was observed in both strains of mice. This decrease persisted even during the 5 min recovery period. When seizures were prevented by Na phenobarbital or glycine, the activation of phosphorylase was either completely prevented (by a non‐anaesthetic dose of phenobarbital) or reduced (by glycine). The present results have demonstrated that changes in glycogen metabolism occurring during homocysteine seizures differ distinctly from those previously found during seizures induced by methionine sulphoximine, a substance structurally related to homocysteine.
POLYUNSATURATED FATTY ACID METABOLISM IN NEUROBLASTOMA CELLS IN CULTURE1
Authors: Yavin E. , Yavin Ziva , Menkes J. H.
Published: October 2006

Abstract—

Neuroblastoma cell cultures took up linoleic and linolenic acids at approximately equal rates, and incorporated them into a variety of lipid fractions, principally cellular phospholipids. Linoleic acid was preferentially incorporated into choline phosphoglycerides, while most of the radioactivity derived from linolenic acid entered ethanolamine phosphoglycerides. There was no evidence for direct transfer of fatty acids between these two phosphoglyceride fractions. When, after the addition of cytosine arabinoside, cell division was arrested, the entry of labelled fatty acids into ethanolamine and serine phosphoglycerides was reduced, suggesting that these lipids are involved in the formation of new cell membranes.

In the ethanolamine phosphoglyceride fraction, phosphatidal ethanolamine (plasmalogen) was the principal acceptor for the higher polyunsaturated fatty acids of the φ 3 series. The ratio of labelled fatty acids entering ethanolamine plasmalogens to that entering ethanolamine phosphoglycerides increased following the addition of cytosine arabinoside, suggesting plasmalogens to be involved in formation of cell processes.

The first step in the metabolism of both linoleic and linolenic acid was the addition of a two‐carbon unit. Conversion of linoleic acid to higher polyunsaturated fatty acids was slower than the conversion of linolenic acid to its higher analogues. This contrasted with the behaviour of dissociated cultures of normal brain cells which were able to form higher analogues of linoleic and linolenic acids at nearly equal rates.
THE EFFECTS OF AGE AND ALCOHOL ON (Na++ K+)‐ATPASE ACTIVITY OF WHOLE HOMOGENATE AND SYNAPTOSOMES PREPARED FROM MOUSE AND HUMAN BRAIN
Authors: Sun A. Y. , Samorajski T.
Published: October 2006

Abstract—

Whole homogenates of mouse brain and nerve‐ending fractions of mouse and human brain were obtained at various age levels representative of maturity and old age. The mice were 3, 8 and 26–29 months old and the humans ranged in age from 19 to 84 y. Measurements of (Na++ K+)‐ATPase in whole brain homogenate of mouse did not reveal any significant differences in relation to age. However, the ability of ethanol at various concentrations to inhibit membrane‐bound synaptosomal (Na++ K+)‐ATPase was significantly greater in older mice and humans. The data are interpreted as indicating a change in the property of synaptic membranes as a consequence of advancing age.
SUPEROXIDE DISMUTASE OF MAMMALIAN NERVOUS SYSTEM
Authors: Fried R. , Mandel P.
Published: October 2006

Abstract—

Superoxide dismutase was assayed in portions of the nervous system (a) by inhibition of tetrazolium reduction by oxygen radicals, generated enzymically, and (b) by inhibition of tetrazolium reduction by oxygen radicals generated by oxidation of NADH in presence of phenazine methosulphate. Superoxide dismutase activity was found in beef brain, retina and adrenal medulla, as well as in brain, retina and lungs of adult and of newborn rats. Preliminary experiments with rats exposed to hyperbaric oxygen showed no alteration of enzyme activities in tissues of newborn and adult animals. The possible role of superoxide dismutase in the nervous system is discussed.
FUNCTIONAL COMPARTMENTS OF ADENINE NUCLEOTIDES SERVING AS PRECURSORS OF ADENOSINE 3′,5′‐MONOPHOSPHATE IN MOUSE CEREBRAL CORTEX
Authors: Skolnick P. , Daly J. W.
Published: October 2006

Abstract—

Cyclic AMP accumulates in cerebral cortical slices from the C57B1/6J mouse incubated with the following stimulatory agents: norepinephrine, adenosine, veratridine and adenosine‐biogenic amine combinations. The results with slices labelled with radioactive adenine or adenosine provide evidence for the existence of distinct functional compartments of adenine nuclcotides which serve as precursors of cyclic AMP on stimulation with specific agents. Thus, in slices labelled with [14C]adenine or [3H]adenosine the ratio of [14C] to [3H]cyclic AMP was dependent on the stimulatory agent; with veratridinc the ratio was 1.4 while with adenosine the ratio was 3.0. In addition, a greater than 2‐fold difference in the ratio of endogenous/radioactive cyclic AMP was observed in adenine or adenosine‐labelled slices after incubation with veratridine, norepinephrine, adenosine or adenosine‐amine combinations; the lowest ratios after stimulation with veratridine and the highest after adenosine or adenosine‐amine combinations. The high ratio observed with adenosine was in part due to a quite marked incorporation of the stimulant, adenosine, into the accumulating cyclic AMP. Such distinct functional compartments of cyclic AMP precursors may represent different cell types and/or morphological entities within one cell type.
GANGLIOSIDES OF THE BOVINE NEUROHYPOPHYSIS
Authors: Clarke J. T. R.
Published: October 2006

Abstract—

The gangliosides of the bovine neurohypophysis were isolated and partially characterized. In terms of lipid‐sialic acid, the concentration of gangliosides in the tissue was 1465 nmol/g wet wt. On the basis of chromatographic properties, sugar composition and the products of neuraminidase‐treatment, the principal ganglioside (approx. 51 per cent of the lipid‐sialic acid) was identified as N‐acetylneuraminylgalactosyl‐ N‐acetylgalactosaminyl‐(N‐acetylneuraminyl)‐galactosyl‐ glucosyl‐ceramide (GDta). The gland also contained galactosyl‐N‐acetylgalactosaminyl‐(N‐acetylneuraminyl‐ N‐acetylneuraminyl)‐galactosyl‐glucosyl‐ceramide (GDtb), and a mixture of N‐glycolyl‐neuraminic acid‐containing disialogangliosides with unknown structures, in addition to smaller quantities of galactosyl‐N‐acetylgalactosaminyl‐(N‐acetylneuraminyl)‐ galactosyl‐glucosyl‐ceramide (GM1) and two glucosamine‐containing monosialogangliosides. Stearic acid was the principal fatty acid in all the gangliosides.
THE STIMULATION OF ARGININE PHOSPHOKINASE IN LOBSTER AXONS BY GABA
Authors: Maki Y. , Cooper J. R.
Published: October 2006

Abstract—

GABA at physiological concentrations has been shown to stimulate the synthesis of arginine phosphate in lobster walking nerves. This effect can be observed both in intact axons and in axonal homogenates. The stimulatory activity of GABA on the synthesis of arginine phosphate appears to be on the Vmax of arginine phosphokinase whereas in the reverse reaction the effect is referable to the Km of ADP.
A COMPARISON OF THE EFFECTS OF SCORPION VENOM TITYUSTOXIN AND OUABAIN ON THE RELEASE OF ACETYLCHOLINE FROM INCUBATED SLICES OF RAT BRAIN1
Authors: Gomez M. V. , Diniz C. R. , Barbosa T. S.
Published: October 2006

Abstract—

The increase in the release of acetylcholine (ACh) from cortical slices of rat brain elicited by the depolarizing agents, ouabain and tityustoxin (TsTX) was compared in the presence of tetrodotoxin, an inhibitor of Na+ transport and of ethyleneglycol tetraacetic acid, a specific chelator of Ca2+. TsTX stimulated the release of ACh independently of K1 but required both Na+ and Ca2+. Unlike ouabain, TsTX failed to inhibit the Na+, K+ ‐ATPase of rat brain homogenates. The uptake of 24Na+ and of 45Ca2+ by the slices was significantly enhanced by TsTX over the entire incubation period during which this process was compared to TsTX‐free controls. A hypothesis of TsTX action is proposed which differs from that necessary to explain the ACh releasing effect of ouabain.
AMINO ACID TRANSPORT INTO THE CEREBROSPINAL FLUID OF THE RAT1
Authors: Franklin G. M. , Dudzinski D. S. , Cutler R. W. P.
Published: October 2006

Abstract—

The concentrations of glycine and 6 other amino acids have been assayed in the CSF and plasma of the rat, and regional heterogeneity of CSF amino acid concentration has been found. Steady state flux rates into the cranial and spinal fluid compartments were determined during perfusion with amino acid free medium. The transfer of glycine from blood into both the cranial and spinal subarachnoid fluids was saturable with only several‐fold elevations of plasma glycine. The results are discussed with regard to the putative neurotransmitter function of glycine in the spinal cord.
ON THE ACTIVATION OF PLASMA MEMBRANE ECTO‐ENZYMES BY TREATMENT WITH NEURAMINIDASE
Authors: Trams E. G. , Lauter C. J. , Banfield W. G.
Published: October 2006

It had been proposed that sialyl‐residues on the surface of the cell control the activity of certain plasma membrane ecto‐enzymes. We have tested the effects of several established (or presumptive) ecto‐enzymes in tissue cultures of CNS‐derived cells.

Application of neuraminidases to cultured mouse neuroblastoma (N‐18), neonatal Syrian hamster astrocytes (NN), human astrocytoma (Cox clone) and two lines of primary mouse astroblasts failed to change the activity of ecto‐ATPase and 5′‐nucleotidase. Only two of the seven neuraminidase preparations produced marked or moderate increases in inorganic pyrophosphatase, p‐nitrophenylphosphatase and cholinesterase. We have concluded that the stimulation of these enzymes was not due to removal of sialyl‐residues. We suggest that contaminants (haemolysins?) in neuraminidase preparations of Clostridium perfringens increased membrane permeability and facilitated substrate‐product translocation.
CHEMICAL COMPOSITIONS OF BRAIN AND MYELIN IN TWO PATIENTS WITH MULTIPLE SULPHATASE DEFICIENCY (A VARIANT FORM OF METACHROMATIC LEUKODYSTROPHY)1
Authors: Eto Y. , Meier C. , Herschkowitz N. N.
Published: October 2006

Abstract—

The lipid composition of the brain, including myelin, was studied in detail in two cases with a variant form of metachromatic leukodystrophy (multiple sulphatase deficiency type).

In the white matter, the sulphatide concentration was 3–4 times higher than the normal level in both cases. There was a significant accumulation of cholesterol sulphate in the brain, liver and kidney of both cases. The ganglioside pattern in the grey and white matter was abnormal, with a higher proportion of GM3, GM2 and GD3‐gangliosides. Non‐lipid hexosamine contents were increased 1.5‐2 times in brain, 8–10 times in liver and 2–3 times in kidney. Increased amounts of glucocerobroside, ceramide lactoside and ceramide trihexoside were present in grey and white matter of both cases.

Recovery of purified myelin from two patients’brains was much less than from control (1–20% in case 1 and 20–30% in case 2). The lipid composition of myelin was almost normal except for a higher proportion of sulphatide, with a decreased amount of cerebroside. The fatty acid compositions of myelin sulphatide and sphingomyelin were almost normal, while non‐hydroxy fatty acids of cerebroside contained less long‐chain fatty acids, as characterized by a significant increase of C16:0 and C18:0 fatty acids. The myelin polypeptide pattern by SDS‐disc gel electrophoresis showed a relative decrease of basic protein and of proteolipid protein.

A possible mechanism of myelin loss in MSD is discussed.
THE EFFECTS OF PHENYLKETONURIC AND OTHER METABOLITES ON SULFATED GALACTOCEREBROSIDE SYNTHESIS IN VIVO AND IN CULTURE
Authors: Sprinkle T. J. , Rennert O. M.
Published: October 2006

Abstract— Sulfated galactocerebroside synthesis was examined in vitro in mouse spinal cord cultures. This system permitted the study of the effects of phenylketonuric metabolites upon synthesis of a specific myelin component, sulfatide, formed early in postnatal development in mice. A significant reduction of Na235SO4 incorporation into myelin sulfatide was observed when spinal cord cultures were grown in the presence of 1000 μm‐l‐phenylalanine and 500 μm‐phenylpyruvate (51 and 700%, respectively). No reduction was observed with β‐phenyllactate (300 μm and) phenylacetate (250 μm). Light microscopy indicated that the phenylpyruvate and phenylalanine treated cultures were less extensively myelinated compared to control and β‐phenyllactate or phenylacetate treated cultures. The reduction of sulfatide synthesis by phenylpyruvate was shown to be reversible.

Intracerebral bilateral injections (8 μg) of l‐phenylalanine, phenylpyruvate, α‐ketobutyrate, α‐ketoisocaproate, α‐ketoisovalerate, β‐phenyllactate, and phenylacetate in mice 8–15 days old, followed by i.p. administration of radioactive sulfate, resulted in significantly reduced incorporation (all P < 0.05) of sulfate into brain sulfatides with all compounds tested with the exception of β‐phenyllactate and phenylacetate. In adult mouse, phenylpyruvate treatment also resulted in a significant decrease in labelling of brain sulfatide.

The effects of phenylpyruvate and other metabolites upon pyruvate oxidation in mouse brain homogenates were examined by measuring 14CO2 release from [1‐14C]pyruvate. Both phenylpyruvate and α‐ketoisocaproate at 1 × 10‐3 resulted in a decrease in 14CO2 produced, while phenylacetate and β‐phenyllactate had no effect.

Sulfate incorporation into sulfatide was reduced by α‐ketoisocaproate and phenylpyruvate, and to a lesser extent by phenylalanine, α‐ketobutyrate, and α‐ketoisovalerate. Phenyllactate and phenylacetate had no effect, either in vivo, or in culture. This order of effectiveness may be related in part to the effects of these compounds on pyruvate oxidation.
THE EFFECT OF DIABETES, INSULIN AND WALLERIAN DEGENERATION ON LEUCINE METABOLISM OF ISOLATED RAT SCIATIC NERVES
Authors: Buse Maria G. , Herlong H. Franklin , Weigand Dorothy A. , Spicer S. S.
Published: October 2006

Abstract– 14CO2 production and 14C incorporation into proteins was studied in isolated rat sciatic nerves during incubation with 0.1 mM‐[1‐14C]leucine. Rats were made diabetic with streptozotocin. Nerves from diabetic rats incubated with glucose oxidized more [14C]leucine than controls. This difference was abolished in the presence of insulin (1 mU/ml). The effects of diabetes and insulin on leucine oxidation could not be demonstrated in the absence of glucose. Insulin stimulated the incorporation of [14C] from leucine into proteins by nerves from controls and diabetic rats.

Nerves undergoing Wallerian degeneration showed a marked increase in DNA content and stimulated incorporation of [14C]leucine into proteins. 14CO2 production from leucine proceeded at 75% of the rate observed in intact nerves. Neither insulin nor diabetes affected leucine metabolism in degenerating nerves.

Neither the extracellular space nor the concentration of free amino acids were significantly different in nerves obtained from control and diabetic rats, except for lower glutamine content in the latter.

In vitro leucine metabolism of nerves is affected by diabetes, insulin and the integrity of the axon. The Schwann cell is suggested as a possible site of the observed changes in leucine metabolism.
PYRUVATE KINASE ISOZYMES IN NEURONS, GLIA, NEUROBLASTOMA, AND GLIOBLASTOMA
Authors: Tolle Susan Willis , Dyson R. D. , Newburgh R. W. , Cardenas Janet M.
Published: October 2006

Abstract– The distribution of pyruvate kinase isozymes (EC 2.7.1.40) was examined in cells and tissues from the central and peripheral nervous system of the rat. Most tissues contain significant quantities of both the K4 (fetal type) and M4 (skeletal muscle type) isozymes plus tetrameric hybrids comprised of various combination of the type M and type K subunits. Retina, for example, contains a five‐mem‐bered hybrid set weighted toward K4, while sciatic nerve and spinal cord have patterns very similar to that of adult brain, consisting predominantly of M4 with small amounts of K4 and K‐M hybrids. This adult pattern is achieved by a gradual shift from a hybrid set dominated by K4 in fetal life, to the pattern at birth at which time the two most prominent bands were M4 and K2M2, and finally to the adult pattern by about 28 days after birth.

Neurons and glial cells were isolated from rat and mouse brains at the various developmental levels. The pyruvate kinase isozyme patterns in the two cell types were similar to each other and to the patterns seen in whole brain homogenates at all ages, indicating similar rates of isozymic maturation in the two cell types.

The correlation of maturation with pyruvate kinase isozyme patterns was further tested in cultures of malignant cell lines. A K‐M hybrid set, weighted toward K4, was seen in two clonal lines of mouse neuroblastoma under normal culture conditions. However, lowering the serum concentration in the culture medium or adding bromodeoxyuridine caused a shift in the patterns toward type M as the cells differentiated, mimicking in part the in vivo maturation of normal cells. On the other hand, a rapidly growing and poorly differentiated line of rat glioblastoma had only K4 under all conditions examined.
EFFECTS OF LYSINE AND THREONINE FORTIFICATION OF BREAD DURING GESTATION AND LACTATION ON OFFSPRING BRAIN LIPID DEVELOPMENT
Authors: Chase H. P. , Welch N. Noreen , Ganong Joanna L. , Jansen G. R.
Published: October 2006

Abstract– Offspring brain lipid development has been studied following the amino acid fortification of wheat diet fed to pregnant and lactating rats. Comparisons are made with a 13% casein diet which contains a similar quantity of protein of known high quality, with a 26% casein diet, and with a standard laboratory diet. Increased maternal energy intake was found, particularly during lactation, with protein quality improvement. Offspring of mothers receiving the unsupplemented bread diet had lower total brain cholesterol, phospholipid, cerebroside‐sulfatide, and (for 4 of the 5 other diets) ganglioside‐NANA levels in comparison to offspring whose mothers received the other diets. Brain cerebroside‐sulfatide and cholesterol concentrations were also lower in the offspring whose mothers received the unsupplemented bread, suggesting impaired myelin formation. Phospholipid and ganglioside‐NANA concentrations were not lower. Fortification of the bread diet with lysine resulted in increases in both the total levels and concentrations of cerebroside‐sulfatide and cholesterol. When both lysine and threonine were added, the cerebroside‐sulfatide and cholesterol levels and concentrations were similar to or greater than values for the two casein diets and the standard laboratory diet. The 26% casein diet did not result in higher lipid values than obtained with the 13% casein diet. This study demonstrates the adequacy of amino acid supplementation of a maternal cereal protein diet in allowing normal offspring brain lipid development.
PROPERTIES OF RAT BRAIN HISTIDINE DECARBOXYLASE
Authors: Palacios J. M. , Mengod G. , Picatoste F. , Grau M. , Blanco I.
Published: October 2006

Abstract– The properties of histidine decarboxylase (l‐histidine carboxylyase EC 4.1,1.22) have been studied in a whole rat brain homogenate. Optimum pH depended upon substrate concentration; the variations of Km and Vmax were determined as a function of pH. pH values lower than 6.0 caused a loss of enzymic activity; activity was stable at pH values higher than 6.0. Enzyme activity was proportional to temperature in the range 30‐45°C; temperature characteristic (μ) and Q10 were determined and thermal inactivation was studied. Addition of pyridoxal 5′‐phosphate increased enzyme activity. Dialysis of homogenates against phosphate buffer caused a partial loss of enzyme activity which could be restored by addition of the coenzyme to the incubation mixture. Enzyme activity was inhibited by α‐methylhistidine and benzene and was unaffected by α‐methyl DOPA. The properties correspond to those of a ‘specific’ histidine decarboxylase. However, the brain enzyme differs from the corresponding enzyme in peripheral tissues in the inability to achieve a total inhibition of activity by dialysis.
THE INFLUENCE OF PRENATAL X‐IRRADIATION ON THE ACTIVITY OF sRNA‐AMTNOACYL SYNTHETASES IN THE DEVELOPING RABBIT BRAIN
Authors: Wender M. , Zgorzalewicz B.
Published: October 2006

—The activities of sRNA‐aminoacyl synthetases (EC 6.1.1) were investigated in the cerebral white and grey matter of rabbits subjected during their prenatal life to a single X‐ray dose of 150 rad. The results of investigations have shown that ionizing radiation acting during intrauterine development of the experimental animal brings about a distinct depression of all sRNA‐aminoacyl synthetase activities in the newborn irradiated litter. During the postnatal development of these animals the activities of some of the synthetases further decreased and even at adulthood, where they are normally very low, their activities were below the control values. The activities of some other synthetases, after the initial depression, showed no further decrease and at adulthood had values comparable to controls. Our results indicate clearly that prenatal exposure to ionizing radiation also affects the step of protein biosynthesis which depends on the activity of sRNA‐aminoacyl synthetases.
CELLS ISOLATED FROM TRYPSIN‐TREATED BRAIN CONTAIN TRYPSIN
Authors: Guarnieri M. , Cohen S. R. , Ginns E.
Published: October 2006

—Neuronal and oligodendroglial cell fractions isolated from trypsinized brain contain trypsin. Neuronal cell bodies contained approximately 5 μg of trypsin/mg of cell protein; oligodendroglial cells had approx 1 μg of enzyme activity. Studies with fluorescein‐conjugated trypsin suggested that least a portion of the fluorescent enzyme was internalized in neurons.
SYNTHESIS AND DEGRADATION OF PROTEIN OF VISUAL RECEPTOR MEMBRANES IN LATERAL EYES OF LIMULUS1
Authors: Krauhs J. M. , Mahler H. R. , Minkler G. , Moore W. J.
Published: October 2006

—The spatial and temporal distribution of labelled protein in lateral eyes of Limulus polyphemus has been followed after injection of l‐[3H]leucine into the pericardial sinus. Labelled protein in the eyes rises for 3 h, for the first hour more rapidly in the cytoplasm but thereafter preferentially in the rhabdomal membranes of the visual receptor cells. In light, the label in the membrane reaches a peak at 3 h whereas in dark the peak is at 6 h. The subsequent decrease in label in light has a half life of about 2 h, but in dark is biphasic with halflives of 2 h and 8 days. These results can be interpreted on the basis that the major labelled protein in the rhabdomal membrane is rhodopsin, the degradation rate of which is enhanced when the membranes are depolarized by light.
BRAIN‐SPECIFIC ANTIGENS IN THE QUAKING MOUSE DURING ONTOGENY
Authors: Jacque C. M. , Jørgensen O. S. , Baumann Nicole A. , Bock Elisabeth
Published: October 2006

Abstract— By means of crossed Immunoelectrophoresis the concentrations of 7 brain‐specific antigens have been investigated during the ontogenic development of normal and Quaking mice. Two proteins, the glial fibrillary acidic protein and the brain‐specific membrane protein D5 were found to be strongly increased in mutant brains. The synaptosomal antigen synaptin (Cl), the 14‐3‐2 protein of neuronal cytoplasm, and the neuronal membrane antigens D1, D2 and D3 were all present at normal levels in mutant brains.
SUB‐CELLULAR LOCALISATION OF ENHANCED LYSINE INCORPORATION INTO CEREBRAL CORTEX PROTEINS IN DARK‐REARED AND LIGHT‐EXPOSED RATS
Authors: Jones‐Lecointe Altheia , Rose S. P. R. , Sinha A. K.
Published: October 2006

Abstract—

Incorporation of lysine into acid‐insoluble material from subcellular fractions of rat cerebral cortex has been studied using double and single‐labelling techniques, in littermates reared for 50 days in the dark and then dark‐maintained or light‐exposed for 1 h. When light‐exposed animals were compared to dark controls the only subcellular fraction from the whole cortex in which lysine incorporation shows a significant elevation (168%, P < 0.05) was located in the ribosomal pellet of the cerebral cortex. A similar comparison of subcellular fractions from visual and motor cortices showed that the elevation was again in the ribosomes and confined to visual cortex only. Motor cortex of light‐exposed animals showed a small depression of incorporation in ribosomes as compared to dark controls. Sub‐fractionation of nuclei from whole cortex preparations showed varying, but non‐significant elevations in light‐exposed animals in all but the histone fraction in which there was negligible incorporation of precursor. It is concluded that enhancement of incorporation of precursor into proteins of the cerebral cortex, which accompanies first exposure to light, is a complex response. At exposure for 1 h it involves a number of particular protein species located in the visual cortex, a major proportion of which are ribosomally bound.
A STUDY OF THE MOLECULAR SIZES AND STABILITY OF CHOLINE ACETY LTRANSFER ASE
Authors: Banns Heather E.
Published: October 2006

Abstract—

Aggregation of the enzyme acetyl‐CoA: choline‐O‐acetyltransferase (ChAc, EC 2.3.1.6) which appears to be homogeneous has been observed. The molecular weight of the most abundant form of ChAc was estimated by gel filtration and sucrose gradient centrifugation to be in the range 58,000‐62,000. The most frequently encountered aggregates were much larger and eluted in the void volume from Sephadcx® G‐100 and G‐150 indicating molecular weights in excess of 400,000. In fact, they were subsequently found to be 1.2 × 106 and 1.9 × 106 by sucrose gradient centrifugation. The percentage of activity associated with high molecular weight ChAc increased with purification, but these aggregates disappeared after storage for 2‐3 weeks at −20°C. The loss occurred independently of any fall in enzymic activity in the preparations examined.
SITE OF BIOSYNTHESIS OF BRAIN‐SPECIFIC PROTEINS IN THE GIANT FIBRE SYSTEM OF THE SQUID
Authors: Alemà S. , Giuditta A.
Published: October 2006

Abstract—

The synthesis of brain‐specific proteins has been examined in perikaryal and axonal regions of the giant fibre system of the squid. After in vitro incubation of stellate ganglia, stellate nerves and isolated giant axons with radioactive amino acids, the labelled soluble proteins have been extracted from the giant fibre lobe, the axoplasm and the axonal sheath of the giant axon and have been separated by gel electrophoresis on a continuous system. In addition, they have been challenged with antisera prepared against the cephalopod brain‐specific proteins L1 and L2 and the resulting precipitate has been resolved by sodium dodecyl sulphate‐gel electrophoresis. Synthesis of these two proteins appears to be restricted to the giant fibre lobe, while an additional discrete protein band (L5) also becomes clearly labelled in the isolated giant axon. Radioactive components migrating in the region of the L1 and L2 proteins are synthesized in the isolated giant axon. They can be distinguished from tbese proteins on the basis of electrophoretic and immunochemical criteria.
THE ACETYLCHOLINESTERASE AND PSEUDO‐ CHOLINESTERASE CONTENTS OF HUMAN PLACENTA AT TERM
Authors: Ruch G. A. , Davis R. , Koelle G. B.
Published: October 2006

The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities of human term placentas have been studied. Perfusion of placentas indicated that most of the AChE and all the BuChE content of the human placenta are due to its blood content. By comparison, rabbit livers, studied similarly, retained most of their contents of both enzymes following perfusion. Histochemical examination or well‐perfused placentas suggests that trapped intact erythrocytes and the stroma of hemolyzed red cells are the probable source of ‘placental’ AChE reported previously.
REGULATION OF CYCLIC ADENOSINE 3′, 5′‐MONOPHOSPHATE CONCENTRATION IN CHICK CEREBRAL HEMISPHERES DURING DEVELOPMENT
Authors: Patton M. W. , Nahorski S. R. , Rogers K. J.
Published: October 2006

Abstract— Investigations have been carried out into developmental aspects of cyclic AMP metabolism and responsiveness to neurohormones in chick cerebral hemispheres. The in vivo cyclic AMP concentration, measured after freeze‐blowing, was found to be highest in the embryonic brain, and changes in the cyclic nucleotide content produced by ischaemia increased with age. The magnitude of the in vivo increases in cyclic AMP produced by isoprenaline and by histamine decreased throughout the first postnatal month. The onset of isoprenaline‐ and histamine‐induced cyclic AMP accumulation in brain slices occurred around 17 days embryonic age, reached a maximum at about 3 days post‐hatch and fell to approx 50% of this response at 28 days of age. Adenosine stimulated cyclic AMP formation to a similar extent at all ages studied.

The activities of adenylate cyclase and cyclic AMP phosphodiesterase of hemisphere homogenates were found to reach maximum near the time of hatching. Since the overall pattern of responsiveness of the cerebral cyclic AMP system to neurohormones does not correlate with these variations in enzyme activities, it is suggested that changes occurring at the synaptic receptor level may explain the developmental variations observed.
DEVELOPMENTAL EFFECTS ON PROTEIN SYNTHESIS RATES IN REGIONS OF THE CNS IN VIVO AND IN VITRO
Authors: Dunlop D. S. , Van Elden W. , Lajtha A.
Published: October 2006

Abstract— Protein synthesis rates have been determined quantitatively in several regions of the nervous system of rats of various ages. The developmental changes in these regions are generally similar with a high rate maintained from several days before birth to about 4 days of age (1.9–2.1% h−1). A decline in the rate ensues thereupon which continues till approx 30 days of age, whence the curve flattens though continuing slowly downward with increasing age. In the young three regions, cerebellum, pineal and pituitary, exhibit exceptionally higher rates (40–50%) than the cerebral hemispheres, pons‐medulla, mid brain or cord, which all display curves of similar magnitude and shape. While the rate in the cerebellum eventually declines with age to within 10% of the rate in cerebral hemisphere, rates in the pineal and pituitary though decreasing remain far above (100%) rates in cerebral hemisphere even in adults.

The rate in vitro for slices of cerebellum follows a pattern similar to that shown previously for cerebral hemispheres: in the very young rates are 70–80% of the in vivo value but decline much more rapidly with age and in adult represent only 10–15% of the rate in vivo.

A markedly different pattern is seen in whole (unsliced) pituitaries wherein in vitro rates parallel in vivo rates with increasing age at approx 70–80% of the in vivo rate. Pineals appear to follow a similar pattern.
THE EFFECTS OF REPEATED‐LYSERGIC ACID DIETHYLAMIDE INJECTIONS ON CATECHOLAMINE LEVELS AND TYROSINE HYDROXYLASE ACTIVITY IN RAT BRAIN REGIONS
Authors: Peters D. A. V. , Tang S.
Published: October 2006

Abstract—

Daily injections of 100 μg/kg of d‐lysergic acid diethylamide (LSD) for 14 days produced a significant decrease in the dopamine level in rat brain corpus striatum which was still apparent 15 days after the last LSD treatment. Further LSD injections did not change the amount of dopamine depletion. In cerebral cortex, 14 days of LSD injections produced a significant decrease in the norepinephrine level and a significant increase in tyrosine hydroxylase activity. The elevated tyrosine hydroxylase activity was still present 15 days after the final LSD injection but only in those animals receiving daily vehicle injections during this period. Pre‐treatment of rats with daily saline injections for 2 weeks before the 2 week period of LSD treatment prevented both the reduced norepinephrine content and elevated tyrosine hydroxylase activity usually found 24 h after the last LSD injection.
EFFECTS OF DIAMINOPROPIONATE, DEOXYADENOSINE, AND THEOPHYLLINE ON STIMULATED FORMATION OF CYCLIC AMP AND GMP BY DEPOLARIZING AGENTS IN SLICES OF GUINEA‐PIG CEREBRAL CORTEX
Authors: SHIMIZU H. , YAMAMURA Y.
Published: October 2006

Abstract—

In incubated slices of guinea‐pig cerebral cortex depolarizing agents such as veratridine and high potassium ions caused 50 to 80‐fold increases of adenosine 3', 5'‐cyclic monophosphate (cyclic AMP) levels and these responses were inhibited about 50% by 2, 3‐diaminopropionate and 2'‐deoxyadenosine: the former is a specific antagonist for glutamate‐elicited accumulation of cyclic AMP and the latter selectively for adenosine‐elicited accumulation. Methylxanthines were powerful ‘inhibitors’toward the responses not only to depolarizing agents but also to glutamate and adenosine. These findings are consistent with the hypothesis that releases of both glutamate and adenosine are involved in the depolarization‐elicited increases of cyclic AMP levels.

Guanosine 3', 5'‐cyclic monophosphate (cyclic GMP) levels in the slices were also elevated by veratridine as well as by glutamate, but always to a lesser extent (8 ∼ 12 times the control value) than cyclic AMP levels were. The responses for cyclic GMP both to veratridine and glutamate were ‘augmented’by methylxanthines and were not inhibited by 2, 3‐diaminopropionate. Thus, glutamate appears to cause the increase of cyclic GMP levels through a different mechanism or site of action from that for cyclic AMP.
THE DEVELOPMENT OF D‐AMINO ACID OXIDASE IN RAT CEREBELLUM
Authors: WEIMAR W. R. , NEIMS A. H.
Published: October 2006

Abstract—

D‐Amino acid oxidase (D‐amino acid: O2 oxidoreductase (deaminating), EC 1.4.3.3; D‐AAO) activity is biochemically undetected in rat brain stem, cerebellum and forebrain until 14 days after birth. Adult levels are attained by day 30 in the brain stem, and by day 36 in the cerebellum. At adulthood, forebrain D‐AAO activity per g wet weight of tissue is less than 2% that of the cerebellum. In contrast to the pattern in the CNS, substantial D‐AAO activity is present in both liver and kidney 2 days before birth and adult levels are approached within 2 weeks of birth. Nonetheless, D‐AAO activities in rat liver, kidney, brain stem and cerebellum are likely to be due to a single enzyme which has properties very similar to the purified hog D‐AAO. The late ontogenesis of D‐AAO activity in cerebellum and brain stem relative to that in liver and kidney parallels reported phylogenetic data.

Histochemical staining for D‐AAO in rat cerebellar cortex is absent until 15 days after birth when activity is first observed in some cells of the external germinal zone and adjacent molecular layer. These cells appear to migrate to a final destination around the Purkinje cell soma and leave processes at the pial surface. By 21 days of age an adult pattern of staining is manifest throughout the cerebellum but it is of weak intensity. The adult pattern includes some staining in the granular layer which seems to be associated with mossy fibers and certain cerebellar glomeruli, and strong staining at the pial surface, in the molecular layer, and in cells surrounding, but not within, the Purkinje cell soma. The data suggest that the biochemical appearance of D‐AAO in developing cerebellum derives from two sources: one associated with differentiation of one of the last cell types to form from the external germinal zone, and the other with maturation of mossy fibers and their synapses (cerebellar glomeruli).
THE EFFECT IN VITRO OF VOLATILE ANESTHETICS ON THE ACTIVITY OF CHOLINESTERASES1
Authors: BRASWELL L. M. , KITZ R. J.
Published: October 2006

Abstract—

Because the mechanism of anesthesia is unknown, the relationship between anesthetics and enzymes essential to brain function may be an important one. Therefore, the effect of 8 volatile anesthetics on the enzymatic activity of solubilized, purified dog brain and human erythrocyte acetylcholinesterase (AChE) and human serum cholinesterase (ChE) was studied in vitro. Serum ChE was found to be insensitive to saturated solutions of all the anesthetics studied. However, brain and erythrocyte AChE were reversibly inhibited in a dose‐dependent manner by all 8 anesthetics in concentrations exceeding those used in clinical practice. Kinetic analysis revealed a mixed (competitive, non‐competitive) type of inhibition with the exception of the ether‐crythrocyte AChE interaction which was characterized by competitive inhibition. Ether and methoxyflurane were found to depress the AChE activity the most and isoflurane and enflurane the least. The concentrations of anesthetic in the gas phase necessary for 50% inhibition of erythrocyte AChE activity (I50) were calculated for 5 anesthetics and found to correlate with their water‐gas partition coefficients. These data suggest that the effect in vitro of volatile anesthetics on the catalytic activity of cholinesterases is a variable one and may be unrelated to anesthetic potency in vivo. The implications of these data concerning anesthetic‐active site interactions are discussed.
EFFECTS OF EPILEPTIC SEIZURES ON BRAIN RIBOSOMES: MECHANISM AND RELATIONSHIP TO CEREBRAL ENERGY METABOLISM
Authors: WASTERLAIN C. G.
Published: October 2006

Abstract—

Epileptic seizures were induced electrically in rats paralyzed and ventilated with oxygen. Dissociation of brain polysomes and increase in ribosomal dimers were observed after multiple (25 or more) seizures, but were not seen after shorter treatments (up to 10 seizures). Polysomal dissociation and dimer formation occurred in vivo and were accompanied by decreased amino acid incorporation into brain proteins in cell‐free systems in vitro. These events paralleled changes in brain energy reserves rather than changes in behavior.