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P Mandel

Publications and source records attributed to P Mandel.

At least 19 recordsLinked to original sources
PubMed1992

Poly(ADPR)polymerase expression and activity during proliferation and differentiation of rat astrocyte and neuronal cultures.

Poly(ADPR)polymerase (poly(ADPR)P) mRNA and enzymatic activity levels were investigated in primary cultures of rat astrocytes and neurons in the absence or presence of basic fibroblast growth factor (bFGF) and nerve growth factor (NGF), respectively. In cultured rat astrocytes, a biphasic increase in poly(ADPR)P mRNA, associated with enhanced nuclear poly(ADPR)P enzymatic activity, were observed. The first rise in poly(ADPR)P mRNA and enzymatic activity is at the beginning of cell proliferation and the second with the occurrence of cell differentiation. In the presence of bFGF (5 ng/ml) the mRNA peaks and the differentiation-associated poly(ADPR)P enzymatic activity undergoes a 2-fold increase. In neuronal cultures an initial high level of poly(ADPR)P mRNA is followed by a decrease while differentiation is progressively achieved. A limited increase of poly(ADPR)P activity is observed during this phase. In the presence of NGF (50 ng/ml), similar poly(ADPR)P mRNA expression and enzymatic activity patterns are observed. The results suggest that poly(ADPR)P is involved at the onset of nerve-cell proliferation and differentiation.

Animals↗
PubMed1992

GABAA sodium independent receptor sites in a strain of rats presenting generalized non-convulsive seizures.

The role of gamma-aminobutyric acid (GABA), a major inhibitor neurotransmitter in the central nervous system (CNS), is well established in the genesis and the control of epilepsies. The purpose of this work was to study the binding parameters of the Na(+)-independent GABA receptors in the brain of a strain of rats presenting spontaneous generalized non-convulsive seizures. The high- and low-affinity binding sites were evaluated in cerebral cortex, cerebellum, and hippocampus using [3H]muscimol. No significant modification was observed for the Bmax and the Kd of high-affinity binding sites, although a slight decrease of Bmax was noted in the three brain areas in rats with seizures. Concerning the low-affinity binding sites, significant decreases were observed in the values of Bmax in the cortex, cerebellum, and hippocampus of animals with spontaneous seizures, without modification of Kd values. Such changes could be considered to be involved in some of the physiological and behaviour activities observed in this strain of rats.

Animals↗
PubMed1992

Involvement of synaptosomal neurotransmitter amino acids in audiogenic seizure-susceptibility and -severity of Rb mice.

The involvement of synaptosomal neurotransmitter amino-acids in seizure susceptibility and seizure severity was explored. The amino-acid contents of brain synaptosomes were determined in three sublines of Rb mice differing in their response to an acoustic stimulus: Rb1, clonic-tonic seizure-prone, Rb2, clonic seizure-prone, and Rb3, seizure-resistant. Synaptosomes were prepared from 6 brain areas considered to be involved in seizure activity: olfactory bulbs, amygdala, inferior colliculus, hippocampus, cerebellum, pons-medulla. The steady-state levels of GABA and glycine (Gly), inhibitory amino-acids, of taurine (Tau), an inhibitory neurotransmitter of neuromodulator, of aspartate (Asp) and glutamate (Glu), excitatory amino-acids, as well as of serine (Ser) and glutamine (Gln), two precursors of neurotransmitter amino-acids, were determined by HPLC. Low levels of Tau, GABA, and Ser in hippocampus, Gly in amygdala, Glu in hippocampus, inferior colliculus and pons, Gln and Asp in inferior colliculus appeared to correlate with seizure-susceptibility. GABA and Asp in olfactory bulb, Gln in amygdala, hippocampus and pons, ser in olfactory bulb and pons, appeared to be associated either with seizure-severity or -diversity. A strong involvement of hippocampus (Tau, GABA, Ser, Glu, and Gln) and inferior colliculus (Asp, Glu, Gln) in audiogenic seizure-susceptibility, and of olfactory bulb (GABA, Asp) in seizure-severity and/or -diversity is suggested.

Acoustic Stimulation↗
PubMed1979

Effect of cyclic nucleotides on high affinity uptake of L-glutamate and taurine in glial and neuroblastoma cells.

Cultured glial cells (clones NN and I6) and neuroblastoma cells (clones M1 and M1NN) were used to study the effect of cyclic nucleotides on high affinity uptake of L-glutamate and taurine. Treatment of NN cells with a mixture of dBcAMP and BrcGMP for one or two days resulted in a more than 3-fold increase in the Vmax of L-glutamate high affinity uptake. Similar but smaller change was observed in a related glial clone (I6). Effects of cyclic nucleotide derivatives on high affinity uptake of L-glutamate by neuroblastoma cells (clones M1 and M1NN) or of taurine by both glial or neuroblastoma cells were either smaller or absent. Some differences were found in kinetic parameters of uptake of L-glutamate and taurine by original and re-isolated cellls, respectively. It is possible that these differences resulted from co-cultivation of glial and neuronal cells. However, since some values reported in this paper differ to some extent from those published previously, some other factors, such as subcloning, may have been responsible.

Animals↗
PubMed1979

Cholinergic involvement in ethanol intoxication and withdrawal-induced seizure susceptibility.

The enzymes of the cholinergic system have been investigated in discrete brain areas in alcohol-dependent rats, which were still intoxicated or were undergoing withdrawal. The ethanol intoxication resulted in a slight, but significant increase in choline acetyltransferase (CAT) activity in the caudate nucleus both 1 and 7 h after the last dose of ethanol. We also found a significant decrease in CAT activity in the temporal limbic cortex while rats were highly intoxicated. All other brain regions investigated, e.g., cerebellum, pons-medulla, frontoparietal cortex, hypothalamus and septum showed unchanged CAT activity. Rats were also analysed immediately following the onset of a withdrawal-induced audiogenic convulsive seizure where, in addition to the striatum, depressed CAT activity was observed in the hippocampus. In all the analysed situations acetylcholinesterase activity remained unchanged. These results show that ethanol intoxication leads to a perturbation in the synthetic capacity of acetylcholine in certain defined brain structures and that this may have some correlation to the observed behavioural impairments.

Acetylcholinesterase↗
PubMed1979

Effect of concanavalin A on the kinetics of ecto-5'-adenosine monophosphatase (5'-adenosine monophosphate phosphohydrolase) in the outer surface of intact neural cells in culture.

Oncogenic cultured rat C6 astroblastoma cells display strikingly high ecto-5'-adenosine monophosphatase (ecto-5'-AMPase) activity, 4.23 +/- 20 mumol of Pi liberated by intact cells from 3 mM extracellular 5'-AMP (mg of protein-1 h-1, as compared with 0.15 +/- 0.01 for nononcogenic cultured hamster astroblasts. A further rise in C6 cell ecto-5'-AMPase activity occurs with increase in cell density during growth. Less than 2 pg of the lectin, concanavalin A (Con A), bound per cell reversibly inhibits most of the cellular ecto-5'-AMPase activity. Inhibition by Con A binding is independent of cellular temperature. Con A binding suppresses phosphohydrolase activity of a pK=7.4 functional group on the cell surface. A direct proportionality is observed between quantity of Con A bound to the cell surface and simultaneous relative decreases both in Michaelis constant and maximum velocity of ecto-5'-AMPase in the intact cell. The findings suggest that a major consequence of the specific high affinity binding of Con A to the C6 cell surface is the inactivation of the enzyme--substrate complex of ecto-5'-AMPase.

Adenosine Monophosphate↗
PubMed1979

Demonstration of a specific localization of carbonic anhydrase C in the glial cells of rat CNS by an immunohistochemical method.

The localization of carbonic anhydrase C isoenzyme in the central nervous system (CNS) of the rat has been investigated using the indirect immunoperoxidase technique, at both optic and electron microscopic levels. Evidence is presented for a specific localization of the enzyme in the cytoplasm of the oligodendrocytes and astrocytes. Myelinated fibers show a weak staining. The positive reaction is restricted to the cytoplasmic areas of the myelin sheath and does not appear in the compact myelin. Neuronal cell bodies do not stain at all. A strong positive reaction to the antiserum was also observed in the choroid plexus.

Animals↗
PubMed1979

Similarities between cysteinesulphinate transaminase and aspartate aminotransferase.

A method for the purification of two cysteinesulphinate transaminases, A and B (EC 2.6.1), is described. These enzymes catalyse the conversion of cysteinesulphinic acid to beta-sulphinyl pyruvate. The final preparations are homogeneous by polyacrylamide gel electrophoresis, sodium dodecyl sulphate-polyacrylamide gel electrophoresis and isoelectrofocusing. The molecular weight of the subunits is 41 000 for cysteinesulphinate transaminase A and 43 400 for B. Both enzymes are unspecific, as L-asparate, L-glutamate and L-cysteic acid serve as substrates in addition to L-cysteinesulphinic acid. Cysteinesulphinate transaminase A has a Km of 9.8 mM for cysteinesulphinic acid and 0.25 mM for aspartic acid, whereas the B enzyme has a Km of 6.5 mM for cysteinesulphinic acid and 1.4 mM for aspartic acid. The Vmax values of the A and B enzymes are respectively 7.1 and 6.2 mmol h-1 mg-1 protein for aspartic acid and 45 and 9.3 mmol h-1 mg-1 protein for cysteinesulphinic acid. Both enzymes exhibit maximum activity at pH 8.6. A high specific activity is found in optimal conditions for these two transaminases, the pI values being 9.06 and 5.70 for cysteinesulphinate transaminase A and B respectively. These results have been compared with those already obtained for purified aspartate aminotransferase. Similarities in the pathways of taurine and gamma-aminobutyric acid (GABA) metabolism are discussed.

Aging↗
PubMed1979

Effects of amino acids on calcium uptake by glial and neuroblastoma cells.

The uptake of [45Ca] has been studied in clonal glial and neuronal cells. It was somewhat more efficient in the neuroblastoma clone M1 compared to glial clones. In all cases [45Ca] uptake was shown to depend on the phosphate concentration in the incubation medium. It was decreased by the ionophore A 23187 at 200 microM concentration in both neuronal and glial clones. The influence of amino acids some of which are putative neurotransmitters was investigated; the interactions between [45Ca] uptake and these amino acids were related to their concentration and the type of cells used (neuronal or glial). L-aspartate and taurine for example had two opposite effects on [45Ca] uptake by the glial clone NN at two different concentrations; they could therefore play a role in the control of calcium level in the synaptic cleft.

Amino Acids↗
PubMed1979

GABA transaminase inhibitors.

In summary, several branched-chain fatty acids appeared to be competitive inhibitors of GABA-T and non-competitive inhibitors of SSADH. These compounds produce an increase in brain GABA level, and for two of these it was shown that the increase differs among various brain areas. An increase of GABA cannot be obtained by inhibition of SSADH. The increase in brain GABA seems to correlate with the anticonvulsant activity of branched-chain fatty acids.

4-Aminobutyrate Transaminase↗
PubMed1979

GABA binding processes in rat brain and liver.

Although these studies have provided some further insight into GABA binding processes associated with transport and receptor-activation, such attempts remain limited due to the lack of specificity of the ligands used to displace these components. Thus, BMI appeared to interact with both transport and synaptic receptor sites for GABA. Perhaps certain GABA-agonists (e.g., muscimol, isoguvacine) will be shown to interact more specifically with synaptic GABA-receptors? So-called "specific" binding of GABA and its analogues, or antagonists might not be the issue to be kept in focus in this type of experiment, especially since it cannot be separated into presynaptic, postsynaptic and non-synaptic components. The specificity of an interaction of ligand with membrane site may be determined by other requirements of the particular system concerned. In any case, it seems essential to examine the binding sites, themselves, in order to define more clearly which of these are involved in receptor-activation and in uptake. An approach involving the isolation and purification of GABA-receptors should provide evidence for specific binding of GABA to its postsynaptic receptors.

Animals↗