Search PubMed⌕ Search

Biomedical subjects

P Mandel

Publications and source records attributed to P Mandel.

At least 73 records · Page 4Linked to original sources

Long lasting effect of a single audiogenic seizure on GABA turnover rates and steady-state levels.

GABA turnover rates (TOR) and steady-state levels (SSL) were determined, 16-18 h after a single acoustic stimulation, in 15 brain areas of 3 mouse sublines. Each subline differs in its response to an acoustic stimulation (Rb1 mice are clonic-tonic seizure-prone, Rb2: clonic seizure-prone, Rb3: seizure-resistant). TOR and SSL were compared to those of unstimulated control mice and to those of repeatedly stimulated mice of the same subline. Following a single acoustic stimulation long-lasting alterations of GABA metabolism, mainly large alterations of GABA TOR, are observed. Most of the effects elicited after repeated stimulations, either on SSL or TOR, are not those of the last stimulation and repeated seizures (and/or stimulations) strengthen the effect of a single one. It appears that, for each of the Rb sublines, a specific and quite simple profile of the alterations of GABA metabolism in response to a single or repeated audiogenic seizures (and/or stimulations) can be given. The global analysis through the correlation of GABA TOR and SSL gives an indication that the alterations of the parameters of the correlation observed are to be allocated to the audiogenic seizures. Furthermore the tonic and clonic components of the audiogenic seizures can be distinguished.

Acoustic Stimulation↗

Alterations of serotonin neurotransmission and inhibition of mouse-killing behavior: III. Effects of minaprine, CM 30366 and SR 95191.

Three closely related aminopyridazine derivatives: minaprine [3-(2-morpholino-ethylamino)-4-methyl-6-phenyl pyridazine, dihydrochloride], CM 30366 [3-(2-morpholino-ethylamino)-4-methyl-6-(4-hydroxyphenyl) pyridazine, hydrobromide] and SR 95191 [3-(2-morpholino-ethylamino)-4-cyano-6-phenyl pyridazine] were examined for their inhibitory effects on mouse-killing behavior (MKB). Three groups of killer rats were used: spontaneous killer rats (K rats) and nonkillers which became killers following para-chlorophenylalanine (PCPA) treatment or electrolytical destruction of the dorsal and median raphe nuclei. When given intraperitoneally (IP), the three drugs inhibited MKB of K rats without sedation. When given orally, minaprine showed no antimuricidal effect in K rats. After chronic IP administration of minaprine, MKB inhibition in K rats decreased after 25 days of treatment, probably because serotonin receptors became subsensitive. Minaprine and SR 95191, a derivative of minaprine, are inhibitors of type A monoamine oxidase (MAO), whereas CM 30366, a metabolite of minaprine, has no effect on MAO activity. SR 95191 displayed a similar MKB inhibition in the three groups of killer rats, and in this respect, it behaved like other type A MAO inhibitors. Minaprine and CM 30366 were less efficient in their antimuricidal effect in PCPA-treated and raphe-lesioned killer rats as compared with spontaneous killer rats. Moreover, the time courses of MKB inhibition and MAO A inhibition by minaprine did not correlate. The effects of minaprine on MKB seemed not related in a simple way to an alteration of serotonin level through MAO A inhibition, and rise the question of an alternative mechanism of antimuricidal action, until now unknown.

Administration, Oral↗

Modulation of adenylate cyclase activity in bovine lens epithelial cells.

Adenylate cyclase activity of bovine lens epithelial cells is activated by guanine nucleotides or fluoride. Additional activation to that of guanylylimidodiphosphate [Gpp(NH)p] was induced by isoproterenol. Insulin was found to inhibit adenylate cyclase activity. Adenosine at low concentrations (5-50 nM) increased adenylate cyclase activity, while at high concentrations it lowered the activity of the enzyme. The occurrence of R and P adenosine sites in lens epithelial cells is suggested. Like other tissues, lens epithelial cells possess a transduction system (adenylate cyclase-G protein complex) for external messages.

Adenosine↗

Regulation of protein adenosine diphosphate ribosylation in bovine lens during aging.

Adenosine diphosphate-ribosyltransferase (ADPRT) and poly-ADP-ribose glycohydrolase (poly-ADPRG) activities were investigated in the different structures of bovine lenses. These activities and protein ADP ribosylation were detected only in the lens epithelium proliferative layer. The poly-ADPR glycohydrolase activity decreased, but the poly-ADPR polymerase activity increased during aging. In lens epithelial cells of older animals, the poly-ADP-ribose level and average chain length decreased but the chain number increased. Involvement of DNA break accumulation during aging in the increase of ADPRT activity of lens epithelial cells is discussed.

Aging↗

[Phosphorylation of cytoplasmic poly (ADP-ribose) polymerase linked to free ribonucleoprotein particles by an associated protein kinase C].

Considering the eventuality of an interaction between the two post-translational modifications, phosphorylation and ADP-ribosylation, we investigated the possibility of phosphorylation of the mRNP polyADPR polymerase by a protein kinase C associated to these particles. We demonstrated that cytoplasmic poly (ADP-ribose) polymerase associated with ribonucleoprotein particles containing silent mRNA is phosphorylated by a specifically activated endogenous protein kinase C which in turn induces an inhibition of the polymerase activity. In the absence of protein kinase C activators the mRNP polyADPR-P is also phosphorylated but without changes of its enzymatic activity.

Blotting, Western↗

An experimental study of fetal alcohol syndrome in the rat: biochemical modifications in brain and liver.

Maternal alcohol consumption produces various abnormalities in the offspring, termed fetal alcohol syndrome. We investigated various biochemical modifications occurring in the brain and the liver of pups born to alcohol-consuming rats. The parameters analysed were: superoxide dismutase, a protector against free radicals injury, enolase isoenzymes as markers of nerve cell maturation, glutamine synthetase involved in ammonia detoxification, alcohol and aldehyde deshydrogenases in order to evaluate the contribution of acetaldehyde teratogenicity and ATPase activities involved in ion and neurotransmitter transport. Activities of all these enzymes were decreased in the brain even when alcohol was withdrawn from the mother diet either during pregnancy or lactation. Activities were also decreased in the liver, except enolase and alcohol deshydrogenase activities, which were increased, suggesting possible adaptative events in the presence of alcohol. It seems likely that the multiple alterations observed in experimental fetal alcohol syndrome may be caused by free radicals following decreased superoxide dismutase activity in addition to the toxicity of alcohol and its metabolites.

Adenosine Triphosphatases↗

Genetically-determined responses of central cholinergic markers: the effects of ethanol on inbred strains of mice.

The present study investigated differences in cholinergic function which might contribute to genetic differences in the effects of ethanol on inbred mice. Choline acetyltransferase (ChAT), acetylcholinesterase (AChE) activity and [3H]-quinuclidinyl benzilate (QNB) binding were assessed in several brain areas after administration of ethanol (4.6 g/Kg). ChAT in striatum and septum of C57BL/6 mouse strain exhibit greater sensitivity to ethanol as compared to BALB/c mouse strain. While BALB/c limbic system and related structures showed greater sensitivity to ethanol as compared to C57BL/6 strain. Our previous studies indicated that acute ethanol administration in C57BL/6 mice increased striatal ChAT activity (up to 22% with 60 min latency, Durkin et al., 1982). This augmentation in ChAT activity induced by ethanol was associated with non-synchronous decreases in kinetic characteristics of QNB binding in striatum. In contrast, no such changes were seen in BALB/c striatum (except we noted an increase in Kd up to 90 min after acute ethanol treatment). Similar significant increases in ChAT activity were also observed in C57BL/6 septum 165 min after ethanol administration. However, the septum in BALB/c mice did not exhibit comparable changes. Ethanol did increase ChAT activity in several brain areas of both strains. The areas included the hippocampus, temporal limbic cortex and piriform cortex or paleocortex. Interestingly, the latencies to increased ChAT activity in these areas were much shorter in BALB/c than in C57 mice. The kinetic characteristics of QNB binding sites (Bmax and Kd) and AChE activity were unchanged in all brain areas and did not differ by strain except as otherwise indicated. These data indicate that genetic differences in ethanol preference and sensitivity in these strains are accompanied by differential sensitivity of ChAT to acute ethanol. Genotypic variations in dopaminergiccholinergic interactions in striatum and hippocampus (Durkin et al., 1983), and septum (Kempf et al., 1985), temporal limbic and piriform cortex, could contribute to genetic differences in cholinergic sensitivity to ethanol. In addition, different blood-brain barrier and membrane properties might also contribute to genetic differences in the sensitivity of cholinergic function to ethanol. The differential effects on ChAT activity might participate in genetic differences in memory disorders (limbic system and related structures) and motor incoordination (basal ganglia) following high dose alcohol administration.

Acetylcholinesterase↗

Ethanolamine base exchange enzymatic activities in spontaneous transformed glial cell lines. Effect of dibutyryl cyclic AMP treatment.

Cultured astrocytes derived from neonatal rats (normal cells) displayed maximal ethanolamine base exchange enzymatic activity (EBEE) when cultures reached confluency and cells almost ceased to divide. At this stage, ethanolamine phosphotransferase (EPT) and choline base exchange enzyme (CBEE) activities reached a plateau. In spontaneously transformed glial cells, no differential activity variation either between EPT and CBEE, or between EPT and EBEE was observed. The EBEE activity was mainly localized in the microsomal fraction and was completely absent from plasma membranes. Dibutyryl cyclic AMP (db-cAMP) treatment of the transformed cells reversed the pattern of these activities to that of normal cells. Moreover, treatment of the transformed cells with medium conditioned by normal astroblasts markedly increased EBEE activity. This study demonstrates that (i) variation of EBEE activity during cell growth differs in normal and in transformed cultured glial cells. (ii) EBEE activity may be modulated via both db-cAMP and normal cell conditioned medium. Our findings suggest a possible implication of EBEE in the maturation and contact inhibition of cell growth.

Animals↗

Unexpected stimulation of mitochondrial ADP-ribosylation by cyanide.

Cyanide, the classical inhibitor of the mitochondrial respiratory chain at site III, stimulates ADP-ribosylation of a number of mitochondrial proteins, the major protein being the 50-55 kDa band. Sodium azide, sharing the same inhibitory site, does not have the same effect. Rotenone or antimycin A have no influence on mitochondrial ADP-ribosylation. Data suggest that no apparent correlation exists between oxidoreductase function and protein ADP-ribosylation. Purified nuclear poly(ADP-ribose) polymerase activity was not affected by cyanide. The cyanide effect on mitochondrial ADP-ribosylation seems intriguing and may be attributed to NAD+-CN complex formation, since NAD reacts with cyanide at pH greater than 8 with N-substituted nicotinamide which may prevent inhibition of ADP-ribosylation.

Adenosine Diphosphate Ribose↗

Studies on benzodiazepine receptor subtypes in a model of chronic spontaneous petit mal-like seizures.

Among the large variety of epilepsy models, differences in binding parameters on benzodiazepine (BZD) receptors could be demonstrated in some of them. A new model of petit mal-like seizures occurring spontaneously has been described in a strain of Wistar rats. The purpose of this study was to investigate the binding parameters on 'central' type and 'peripheral' type BZD receptor sites in epileptic and non-epileptic animals of this strain. Thus, using [3H]flunitrazepam as ligand, no modification was observed for 'central' type BZD sites in cortex, cerebellum and hippocampus. Nevertheless, using [3H]Ro 5-4864 as ligand, an important increase (125-150%) in the affinity constant on 'peripheral' type BZD sites was observed in epileptic rats, namely a lower affinity for the ligand on this receptor. Finally, no change occurred in the ratio between 'central' and 'peripheral' BZD receptor site apparent numbers.

Animals↗

Cytoplasmic poly(ADP-ribose) polymerase and poly(ADP-ribose) glycohydrolase in AEV-transformed chicken erythroblasts.

Poly(ADP-ribose) polymerase and poly(ADP-ribose) glycohydrolase activities were both investigated in chicken erythroblasts transformed by Avian Erythroblastosis Virus. Respectively 21% and 58% of these activities were found to be present in the post-mitochondrial supernatant (PMS). Fractionation of the PMS on sucrose gradients and poly(A+) mRNA detection by hybridization to [3H] poly(U) show that cytoplasmic poly(ADP-ribose) polymerase is exclusively localized in free mRNP. The glycohydrolase activity sedimented mostly in the 6 S region but 1/3 of the activity was in the free mRNP zone. Seven poly(ADP-ribose) protein acceptors were identified in the PMS in the Mr 21,000-120,000 range. The Mr 120,000 protein corresponds to automodified poly(ADP-ribose) polymerase. A Mr 21,000 protein acceptor is abundant in PMS and a Mr 34,000 is exclusively associated with ribosomes and ribosomal subunits. The existence of both poly(ADP-ribose) polymerase and glycohydrolase activities in free mRNP argues in favour of a role of poly(ADP-ribosylation) in mRNP metabolism. A possible involvement of this post translational modification in the mechanisms of repression-derepression of mRNA is discussed.

Animals↗

Concentrations of physiologically important metal ions in glial cells cultured from chick cerebral cortex.

Energy dispersive x-ray fluorescence and atomic absorption spectroscopy were used to determine the concentrations of Mg, Ca, Mn, Fe, Zn, and Cu in primary cultures of astroglial cells from chick embryo cortex in chemically defined serum-free growth medium. The intracellular volume of cultured glia was determined to be 8.34 microliter/mg protein. Intracellular Mn, Fe, Zn, and Cu in these cells were ca. 10-200 microM, or 20-200 times the concentrations in the growth medium. Mg2+ was 7 mM in glial cells, only four-fold higher than in growth medium. Glutamine synthetase (GS), compartmentalized in glia, catalyzes a key step in the metabolism of neurotransmitter L-glutamate as part of the glutamate/glutamine cycle between neurons and glia. Hormones (insulin, hydrocortisone, and cAMP) added to growth medium differentially altered the activity of GS and the intracellular level of Mn(II), but not Mg(II). These findings suggest the possibility that glutamine synthetase activity could be regulated in brain by the intracellular levels of Mn(II) or the ratio of Mn(II)/Mg(II), which may in turn be controlled indirectly by means of transport processes that respond to hormones or secondary metabolic signals.

Animals↗

Alterations of serotonin neurotransmission and inhibition of mouse killing behavior: II. Effects of selective and reversible monoamine oxidase inhibitors of type A.

Three groups of rats were tested for mouse killing behavior after IP injection of selective and reversible type A monoamine oxidase inhibitors. The rats were either spontaneous killers, or non-killers which acquired killing behavior following para-chlorophenylalanine treatment or electrolytical destruction of dorsal and median raphe nuclei. Moclobemide (para-chloro-N-(2-morpholinoethyl)-benzamide), cimoxatone (3-(4-(3-cyanophenyl-methoxy)phenyl)-5-(methoxy-methyl)-2-oxazo lid inone, MD 780515), toloxatone (5-(hydroxymethyl)-3-(3-methylphenyl)-2-oxazolidinone) and amiflamine ((+)-4-dimethylamino-2, alpha-dimethylphenethyl amine, FLA 336 (+)) were used as selective and reversible monoamine oxidase inhibitors of type A. Cimoxatone, toloxatone and amiflamine inhibited mouse killing behavior of spontaneous killer rats without apparent sedation, whereas moclobemide was not efficient at doses which did not decrease locomotor activity. A similar inhibition of mouse killing behavior was obtained in spontaneous and serotonin depleted killer rats. The results are discussed in relation to the behavioral expression of serotoninergic supersensitivity in the three groups of killer rats described earlier using serotonin agonist and uptake inhibitors.

Aggression↗

Cardiocirculatory, hormonal, and metabolic reactions to various forms of ergometric tests.

The sympathoadrenergic reaction is not only dependent on the duration and intensity of work but also on the body position and the involvement of small or large muscle masses. This observation made in field tests comparing different sports disciplines such as swimming, running, or diving encouraged us to investigate this topic under the following laboratory conditions. Twelve healthy sport students participated in ergometric tests on a bicycle ergometer in a horizontal and vertical body position as well as on a treadmill and a swim bench ergometer. The changes of plasma catecholamines (CA) obtained in the different ergometric tests were compared with those cardiocirculatory, metabolic, and hormonal parameters which can be influenced by the sympathoadrenergic stimulation. In the horizontal body position we found a smaller increase of norepinephrine at submaximal and maximal work loads combined with a similar reaction of renin, whereas the diastolic blood pressure and the mean arterial blood pressure increased more. The substrates of lipolysis and aerobic and anaerobic glycolysis did not show obvious differences depending on the body position. In the swim bench test, however, the lactate increase started earlier and was comparatively higher than in the other ergometric tests in which the maximal work load and VO2max were higher. Although a smaller muscle mass was used and a lower maximal oxygen uptake was reached, we did not find statistically different CA values during the swim bench ergometric test compared with the bicycle ergometric test in a horizontal body position. In our ergometric tests, the venous CA levels (especially norepinephrine) were predominantly influenced by the body position.

Adult↗

Cytoplasmic poly(ADP-ribose) polymerase associated with free messenger ribonucleoprotein particles in rat brain.

Poly(ADP-ribose) polymerase associated with free cytoplasmic messenger ribonucleoprotein particles (free mRNP particles) carrying messenger RNA has been characterized in rat brain. There were first-order kinetics for NAD with an apparent Km for NAD of 90.5 +/- 0.70 microM and Vmax of 19.7 +/- 2.8 pmol ADP-ribose incorporated min-1 mg protein-1. Five poly(ADP-ribose) protein acceptors were identified in the Mr 37,000-120,000 range. It is hypothesized that ADP-ribosylation of specific free mRNP proteins might play a role in the derepression and translation of the silent mRNAs of free mRNP particles.

Animals↗