bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biosynthesis of 5‐Aminopentanoic Acid and 2‐Piperidone from Cadaverine and 1‐Piperideine in Mouse
Authors: Callery Patrick S. , Geelhaar Linda A. 
Published: October 2006

Abstract1‐Piperideine, 5‐aminopentanoic acid, and its lactam, 2‐piperidone, were identified as metabolites of cadaverine in 10,000 g mouse liver supernatants to which diamine oxidase had been added. Both metabolites were also found when the cadaverine metabolite 1‐piperideine was incubated with the preparation which suggested that 1‐piperideine is an intermediate in the formation of 5‐ammopentanoic acid and 2‐piperidone. Identification of the metabolites was based on gas chromatography‐mass spectrometric analysis in comparison to authentic standards. Mouse brain homogenates converted 1‐piperideine to 5‐aminopentanoic acid. The results suggest that the metabolic fate of cadaverine may provide precursors of pharmacologically active analogues of GABA.
Measurement of Prostaglandins in the Cerebrospinal Fluid in Cat, Dog, and Man
Authors: Romero Silvia Divinetz , Chyatte Douglas , Byer David E. , Romero J. Carlos , Yaksh Tony L. 
Published: October 2006

AbstractProstaglandins are involved in the modulation of various central functions (neurotransmitters and hypothalamic hormone release, thermoregulation, cerebro‐vascular tone) and their levels increase in pathological situations [subarachnoid hemorrhage (SAH), stroke, convulsive disorders, etc.]. This study, using sensitive and specific antibodies, examined levels of four eicosanoids, Prostaglandins E2 and F2α(PGE2, PGF2α); and the metabolites of PGI2, 6‐keto‐prostaglandin F1α (6‐keto‐PGF1α) and of thromboxane A2, thromboxane B2 (TxB2), in the cerebrospinal fluid (CSF) obtained atraumatically from three species (human, canine, and feline). An assessment of the methodologic procedures (extraction and radioimmunoassay) was carried out. Human lumbar cerebrospinal fluid was shown to contain PGF2α (15–44 pg/ml), 6‐keto‐PGF1α (undetectable to 39 pg/ml), and TxB2 (un‐detectable to 28 pg/ml), whereas PGE2 was undetectable (>18 pg) in all cases. In both animals species the eico‐sanoid concentrations were 3‐to 30‐fold higher than humans for every prostaglandin examined. Although the prostaglandin profile for a given species remained constant (cat, PGE2:6‐keto‐PGF1α:TxB2:PGF2α; dog, TxB2:PGE2:6‐keto‐PGF1α:PGF2α), the absolute levels were found to be lower in the pentobarbital‐anesthetized animals than in conscious cats. The correspondence of the prostaglandin profiles found in cerebrospinal fluid with the profiles reported in the literature in brain homogenates for the same species supports the hypothesis that cerebrospinal fluid levels of prostaglandins reflect the relative rates of synthesis in neural tissue.
Effect of the Jimpy Mutation on Expression of Myelin Proteins in Heterozygous and Hemizygous Mouse Brain
Authors: Kerner Ann‐Louise , Carson John H. 
Published: October 2006

AbstractThe levels of myelin basic protein, proteolipid protein, and 2′,3′‐cyclic nucleotide 3′‐phosphohydrolase (EC 3.1.4.37) in cerebral hemispheres of wild‐type, heterozygous jp/+, and hemizygous jp/Y mice of different ages were determined by radioimmunoassay and immunoblotting. ln jp/Y brain the level of myelin basic protein was 8% that of wild‐type at all ages. All forms of the protein were reduced although the 21.5K Mr form was relatively spared at early ages compared to the 18.5K, 17K, and 14K Mr forms. The level of 2′,3′‐cyclic nucleotide 3′‐phosphohydrolase was. 8% that of wild‐type at all ages, and proteolipid protein was undetectable at any age. These results are consistent with the hypothesis that the jimpy mutation blocks myelin morphogenesis subsequent to incorporation of 21.5K Mr myelin basic protein but prior to incorporation of proteolipid protein. ln jp/+ brain the levels of the three proteins were reduced commensurately to 60–70% those of wild‐type. The deficit was apparent as early as 1.0 days after birth and remained proportionately constant throughout development. These results suggest that in jp/+ mice, X‐chromosome inactivation produces a mosaic population of functionally wild‐type and functionally jimpy oligodendrocytes. The former elaborate normal amounts of myelin but do not completely compensate for the myelin deficit due to the latter.
Experimental Methyl Mercury Neurotoxicity: Locus of Mercurial Inhibition of Brain Protein Synthesis In Vivo and In Vitro
Authors: Cheung Marshall K. , Verity M. Anthony 
Published: October 2006

Abstract:Brain cell‐free protein synthesis is inhibited by methyl mercury chloride (MeHg) following in vivo or in vitro administration. In this report, we have identified the locus of mercurial inhibition of translation. Intraperitoneal injection of MeHg (40 nmol/g body wt) induced variable inhibition of amino acid incorporation into the postmitochondrial supernatant (PMS) harvested from the brain of young (10‐20‐day‐old) rats. No mercurial‐induced disaggregation of brain polyribosomes nor change in the proportion of 80S monoribosomes was detected on sucrose density gradients. No difference in total RNA was found in the PMS. Initiation complex formation was stimulated by MeHg, as detected by radiolabelled methionine binding to 80S monoribosomes following continuous sucrose density gradient centrifugation. After micrococcal nuclease digestion of endogenous mRNA, both in vivo and in vitro MeHg inhibited polyuridylic acid‐directed incorporation of [3H]phenylalanine. However, the in vivo inhibition was no longer observed when [3H]phenylalanyl‐tRNAPhe replaced free [3H]phenylalanine in the incorporation assay. The formation of peptidyl[3H]puromycin revealed no difference from controls. There was significant mercurial inhibition of phenylalanyl‐tRNAPhe synthetase activity in pH 5 enzyme fractions derived from brain PMS of MeHg‐poisoned rats. These experiments revealed that the apparent MeHg inhibition of brain translation in vivo and in vitro is due primarily to perturbation in the aminoacylation of tRNA and is not associated with defective initiation, elongation, or ribosomal function.
Inhibition of Tyrosine Hydroxylase Activity by Serotonin in Explants of Newborn Rat Locus Ceruleus
Authors: Devau G. , Multon M. F. , Pujol J. F. , Buda M. 
Published: October 2006

Abstract: The long‐term regulation of tyrosine hydroxylase (TH) by serotonin has been studied with cultures of newborn rat locus ceruleus explants. The presence of serotonin in the culture medium for a 24‐h period was followed by an inhibition of TH activity in the explants. This effect lasted several days, with a maximal effect 2 days after treatment. Moreover, the decrease was reversible and dependent on the concentration of serotonin used (from 1 μMto 1 mM).The mechanisms of this regulation have been studied using drugs such as those known to act specifically on serotoninergic receptors and those known to interfere with protein synthesis. Thus, the action of serotonin (10−5M)on TH activity was suppressed with equimolar concentrations of serotoninergic antagonists such as metergoline or methiothepin.It was reproduced by quipazine, a drug capable of acting as a serotoninergic agonist. Inhibitors of protein synthesis acting either at the transcriptional or the translational levels can reproduce the inhibition of TH activity by serotonin alone. Furthermore, the effects of one or the other of these compounds and that of serotonin were not additive. This study confirms the hypothesis of an inhibitory control by serotonin on TH activity in the noradrenergic neurons of the locus ceruleus. Serotonin could regulate the synthesis of the enzyme through specific serotoninergic receptors.
Cell Cycle‐Specific Requirement for Mevalonate, but Not for Cholesterol, for DNA Synthesis in Glial Primary Cultures
Authors: Langan Thomas J. , Volpe Joseph J. 
Published: October 2006

AbstractThe requirement for the sterol biosynthetic pathway for the occurrence of DNA synthesis in glial cells and, in particular, the relative roles of cholesterol and of mevalonate have been studied. Primary cultures of developing glial cells were synchronized by reducing the content of fetal calf serum (FCS) in the culture medium from 10% to 0.1% (vol/ vol) for 48 h between days 4 and 6 in culture. Reversal of the resulting quiescent state by the return of the cultures to 10% serum caused after 24 h a marked increase in DNA synthesis, and this increase was prevented by the simultaneous addition of mevinolin, a specific inhibitor of the sterol biosynthetic pathway at the 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase step, at the time of serum repletion. A dose‐dependent reversal of the mevinolin inhibition of DNA synthesis occurred with simultaneous addition of mevalonate to the culture medium. The induction of DNA synthesis by serum repletion, its inhibition by mevinolin, and the reversal of the inhibition by mevalonate were unaffected by a 95% reduction in exogenous cholesterol produced by utilization of lipoprotein‐poor serum (LPPS) rather than FCS. Similarly, return of quiescent cultures to 10% LPPS containing mevinolin and sufficient low‐density lipoprotein (LDL) to raise the cholesterol concentration 80‐fold failed to restore DNA synthesis. In addition, reversal of the mevinolin inhibition of DNA synthesis by mevalonate occurred despite the continuous presence of mevinolin if mevalonate was added as late as 12 h after serum repletion, but not if added after 16 h or more. This temporal aspect of the requirement for mevalonate was unaffected by the presence of a 90‐fold excess of cholesterol, provided as LDL. Thus, these data establish a requirement for mevalonate or for a presumably nonsterol derivative of mevalonate for the occurrence of DNA synthesis in synchronized glial primary cultures, and demonstrate that this requirement is expressed at a specific time in the cell cycle.
Feeding‐Related Circadian Variation in tele‐Methylhistamine Levels of Mouse and Rat Brains
Authors: Oishi Ryozo , Itoh Yoshinori , Nishibori Masahiro , Saeki Kiyomi 
Published: October 2006

AbstractCircadian changes in the brain histamine (HA) and tele‐methylhistamine (t‐MH) levels were studied in mice and rats after adaptation to an alternating 12‐h light/dark cycle (lights on at 0600). Although there was no significant circadian fluctuation of the brain HA levels, the levels of t‐MH, a major metabolite of brain HA, showed a marked circadian variation. In mice, the t‐MH levels were about 80 ng/g from 1200 to 1800 but about two times higher values were obtained from 2400 to 0600 of the next morning. In rats, the t‐MH levels ranged from 24 to 28 ng/g at 0600 and 1200, slightly increased at 1800, and reached at 2400 a peak twice as high as the levels seen during the light period. The t‐MH levels again rapidly decreased during the subsequent 3 h. In mice fasted from 1200, the t‐MH levels did not increase during the period of darkness. When mice were fed at 1200 after a 24‐h fast, a significant increase in the t‐MH levels was observed at 1800. There was no significant circadian variation of the HA and t‐MH levels in the plasma of mice and rats. These results suggest that circadian variation in brain t‐MH levels is related to feeding and possible subsequent changes in elimination of t‐MH from the brain and/or turnover of HA in the brain. This phenomenon should be given due attention when HA dynamics in the brain are being assessed.
Changes in Extracellular Amino Acids During Soman‐and Kainic Acid‐Induced Seizures
Authors: Wade John V. , Samson Fred E. , Nelson Stanley R. , Pazdernik Thomas L. 
Published: October 2006

AbstractExtracellular amino acid levels in the rat piriform cortex, an area highly susceptible to seizure‐induced neuropathology, were determined by means of intracranial microdialysis. Seizures were induced by systemic administration of either soman (O‐1,2,2‐trimethylpropyl methylphosphonofluoridate), a potent inhibitor of acetylcholinesterase, or the excitotoxin kainic acid. Extracellular glutamate levels increased in animals with seizures shortly after administration of either convulsant, but this change was statistically significant only in the case of soman‐treated animals. Extracellular taurine levels increased markedly, reaching two‐and fourfold baseline levels during the second hour of soman‐and kainic acid‐induced seizures, respectively. Taurine levels did not increase in the subpopulation of soman‐treated animals without seizures, a finding indicating that elevation of extracellular taurine level is seizure related. Thus, we propose that taurine efflux may be a physiological cellular response to neuronal changes produced by excito‐toxic chemicals, either directly or as a consequence of seizures.
Delayed Cerebroventricular Metabolism of [125I]Angiotensins in the Spontaneously Hypertensive Rat
Authors: Wright John W. , Sullivan Margaret J. , Bredl Charles R. , Hanesworth Jodie M. , Cushing Laurie L. , Harding Joseph W. 
Published: October 2006

AbstractThis study was designed to evaluate the hypothesis that impaired brain angiotensin signal termination contributes to the sustained blood pressure elevations noted in the genetically hypertensive rat model of human essential hypertension. A technique that combined the intracerebroventricular injection of [125I]angiotensins, followed by focused microwave fixation to stop all peptidase activity and subsequent HPLC analyses, was used for determining half‐lives of [I25I]angiotensin II and [125I]angiotensin III in the ventricular space. The results indicate that the spontaneously hypertensive rat evidenced significantly longer half‐lives for intracerebroventricularly injected [125I]angiotensin II over those measured for the Wistar‐Kyoto and Sprague‐Dawley normotensive rat strains: 45.0, 27.2, and 25.0 s, respectively. This was also true for intracerebroventricularly administered [125I]angiotensin III: 19.5, 11.4, and 9.0 s, respectively. These results support the notion that a dysfunction in central aminopeptidase activity in the spontaneously hypertensive rat may result in prolonged half‐lives of endogenously synthesized angiotensins II and III, which are known to serve as ligands at central angiotensin receptors responsible for the control of cardiovascular function. The extended half‐lives of these ligands may contribute to the sustained elevations in blood pressure observed in this animal model.
Choline Acetyltransferase Activity in the Rat Brain Cortex Homogenate, Synaptosomes, and Capillaries After Lesioning the Nucleus Basalis Magnocellularis
Authors: Santos‐Benito F. F. , González J. L. , de La Torre F. 
Published: October 2006

AbstractStereotaxic lesions of the nucleus basalis magnocellularis were made unilaterally in male Wistar rats with either kainic or ibotenic acid, using the contralateral side as control. Differences in behavior, body weight, and survival were observed between the kainic and ibotenic acid‐treated rats. One week after surgery, the rats were sacrificed and the effect of the lesions on choline acetyltransferase activity was measured in brain cortex homogenate, synaptosomes, and capillaries. In kainic acid‐lesioned rats, choline acetyltransferase activity decreased in homogenate and synaptosomes of the ipsilateral side with respect to that of the contralateral side; but the ibotenic acid lesion, which also reduced the ipsilateral choline acetyltransferase activity in homogenate, showed a rather different effect on the enzymatic activity of the synaptosomes. There were also differences between the effect of kainic and ibotenic acid lesions on choline acetyltransferase activity in the capillaries of the ipsilateral side with respect to that of the contralateral one. However, capillary choline acetyltransferase activity of the treated rats was in both sides three times higher than that of unoperated rats.
Energy Metabolism and Quantal Acetylcholine Release: Effects of Botulinum Toxin, l‐Fluoro‐2,4‐Dinitrobenzene, and Diamide in the Torpedo Electric Organ
Authors: Dunant Yves , Loctin Francoise , Marsal Jordi , Muller Dominique , Parducz Arpad , Rabasseda Xavier 
Published: October 2006

AbstractIn the Torpedo electric organ, a modified nervemuscle system, type A botulinum toxin blocked the release of acetylcholine (ACh) quanta, both neurally evoked and spontaneous. At the same time, the toxin increased the release of a class of small miniature potentials (the subminiature potentials), reduced the ATP and more the creatine phosphate content of the tissue, and impaired the activity of creatine kinase (CK). Thus, we compared this pattern of changes with those provoked by l‐fluoro‐2,4‐dinitrobenzene (FDNB), an efficient inhibitor of CK. As expected, FDNB rapidly inactivated CK, which resulted in a profound depletion of ATP whereas the stores of creatine phosphate were preserved. In addition, FDNB caused conspicuous morphological alterations of nerve endings and ACh depletion. This agent also suppressed evoked and spontaneous quantal release whereas the occurrence of subminiature potentials was markedly increased. Diamide, a penetrating thiol oxidizing substance, provoked first a transient rise in quantal ACh release and then blockade of transmission with, again, production of a large number of subminiature potentials. Creatine phosphate was depleted in the tissue by diamide, the ATP content reduced, and CK activity partly inhibited. The morphology of nerve terminals did not show obvious changes with either diamide or botulinum toxin at the stage of transmission failure. Although the three poisons acted by different mechanisms, this resulted in a rather similar pattern of physiological changes: failure of quantal release and enhancement of subquantal release. These results and experiments on synaptosomes indicated that CK inhibition was probably a crucial mechanism for FDNB but not for diamide or botulinum intoxication. On the other hand, similarities between the effect of the clostridial toxin and those of diamide may suggest that the effects of botulinum toxin in nerve terminals result from a general oxidation of thiols. in parallel damaging energy‐providing enzymes (including creatine kinase) and components responsible for the quantal mode of ACh release.
Synthesis and Transport of Cerebrosides and Sulfatides in Rat Brain During Development
Authors: Koul Omanand , Singh Indrapal , Jungalwala Firoze B. 
Published: October 2006

AbstractSynthesis and transport of nonhydroxy fatty acid (NFA)‐ and hydroxy fatty acid (HFA)‐containing ceramides, cerebrosides, and sulfatides were studied in vivo in rat brain during development. After an intracerebral injection of [3H]serine, incorporation into these lipids of microsomal and myelin membranes was analyzed after HPLC. Distribution of amounts and incorporation of radioactivity were also determined in individual molecular species of these lipids. The results showed that HFA‐ceramides and long‐chain NFA‐ceramides have small pool sizes and rapid turnover rates in the microsomal membranes and are preferentially utilized for the synthesis of long‐chain (≥20:0) HFA‐and NFA‐galactocerebrosides of both microsomal and myelin membranes. Glucocerebrosides are not expressed in myelin and their synthesis in microsomal membranes is predominant before the onset of myelination. With development, synthesis and accumulation of HFA‐cerebrosides increase over NFA‐cerebrosides in both microsomal and myelin membranes. In myelin, incorporation of radioactivity into HFA‐cerebrosides is even higher than that expected by transport alone from microsomal membranes and it is possible that part of the HFA‐cerebrosides in myelin could be due to de novo synthesis by myelin itself. The amount of NFA‐ and HFA‐sulfatides is about equal, both in myelin and microsomal membranes, and this relative proportion does not change with development. Similar relative rates of incorporation of radioactivity into sulfatides of microsomal and myelin membranes are consistent with the notion that both NFA and HFA sulfatides are synthesized in the microsomal (Golgi) membranes and are transported to myelin. In vitro kinetic analysis of both myelin and microsomal galactosyltransferase with different HFA‐ceramide species showed an apparent Km of about 0.12 mM, whereas the Vmax was highest for h24:1 ceramide followed by that for h18:0 and h24:0 ceramides.
Evidence of Glutamatergic Denervation and Possible Abnormal Metabolism in Alzheimer's Disease
Authors: Procter A. W. , Palmer A. M. , Francis P. T. , Lowe S. L. , Neary D. , Murphy E. , Doshi R. , Bowen D. M. 
Published: October 2006

AbstractExcitatory dicarboxylic amino acids previously have been ascribed several functions in the brain. Here their total concentration and proposed neurochemical markers of neurotransmitter function have been measured in brain from patients with Alzheimer's disease (AD) and controls. Specimens were obtained antemortem (biopsy) approximately 3 years after emergence of symptoms and promptly (<3 h) postmortem some 10 years after onset. Early in the disease a slight elevation in aspartic acid concentration of cerebral cortex was observed in the patients with AD. A reduction in glutamic acid concentration of a similar magnitude was found. It is argued that this, together with a decrease in CSF glutamine content and lack of change in the phosphate‐activated brain glutaminase activity of tissue, reflects an early metabolic abnormality. Later in the disease evidence of glutamatergic neurone loss is provided by the finding that in many regions of the cerebral cortex the Na+‐dependent uptake of D‐[3H]aspartic acid was almost always lowest in AD subjects compared with control when assessed by a method designed to minimise artifacts and epiphenomena. Release of endogenous neuro‐transmitters from human brain tissue postmortem did not appear to have the characteristics of that from human tissue antemortem and rat brain.
Lithium Selectively Inhibits Muscarinic Receptor‐Stimulated Inositol Tetrakisphosphate Accumulation in Mouse Cerebral Cortex Slices
Authors: Whitworth P. , Kendall D. A. 
Published: October 2006

AbstractThe in vitro effects of Li on agonist‐ and depolarization‐stimulated accumulation of inositol phosphates were determined in mouse cerebral cortex slices. Of the agents examined, only the cholinergic agonist carbachol produced a significant accumulation of inositol tetrakisphosphate (InsP4) in the absence of Li. Lithium at 5 mM enhanced the accumulation of inositol monophosphate (InsP1) and inositol bisphosphate (InsP2) due to all the stimuli used and potentiated inositol trisphosphate (InsP3) accumulation due to histamine and noradrenaline, although at lower Li concentrations, carbachol‐stimulated InsP3 accumulation was reduced. Li also enhanced InsP4 accumulation in the presence of noradrenaline, histamine, and elevated KG level but, in marked contrast, reduced carbachol‐stimulated InsP4 accumulation with an IC50 of 100 μM. There was a significant time delay between the initiation of carbachol stimulation and the beginning of the InsP4 inhibition due to Li. The phorbol ester 4β‐phorbol 12β‐myristate 13α‐acetate did not mimic the effects of Li. The results suggest that muscarinic receptor‐mediated InsP4 production might be one of the targets for the therapeutic action of Li.