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Biomedical subjects

P Mandel

Publications and source records attributed to P Mandel.

At least 181 records · Page 10Linked to original sources
PubMed1982

Glutamine and glutamate transport in cultured neuronal and glial cells.

The uptake of L-glutamine in neuronal and glial cultures derived from rat cerebral hemispheres was found to be mediated by a low affinity-high capacity mechanism which was concentrative in both cell types; the calculated Km and Vmax were twice as high in glial than in neuronal cultures. In contrast L-glutamate was taken up by a high affinity system which was particularly efficient and concentrative in the glial cells. Different transport mechanisms for L-glutamine appeared to operate in the two cell types: L-glutamine uptake in neurons was sodium-dependent, specifically inhibited by L-glutamine but not affected by high potassium concentrations in the external medium; on the other hand, glial glutamine transport was decreased when potassium concentration increased, was sodium-independent and significantly inhibited by 3 structurally related amino acids. No significant contribution of homoexchange could be detected in either cell type. After [14C]glutamine preincubation, the radioactivity released into the superfusion medium by neuronal cells was increased in the presence of a high potassium concentration; no such effect could be seen in the case of glial cultures. A regulatory mechanism is suggested where astrocyte depolarization and repolarization would channel a flux of glutamine toward the neurons, subsequent to a glutamate flux in the opposite direction.

Animals↗
PubMed1982

High affinity binding sites for gamma-hydroxybutyric acid in rat brain.

The existence of a specific synthesizing enzyme for gamma-hydroxybutyric acid in rat brain has recently been reported. Here, for the first time, we demonstrate the presence of a high affinity, apparently specific binding site for this compound in the same tissue. This binding does not require Na+ and takes place optimally at pH 5.5. The bound gamma-hydroxybutyric acid is not displacable by GABA or baclofen. We report here on some structurally related compounds of GHB with a similar or better binding capacity than GHB itself. The number of binding sites increases with age up to adulthood and differs depending on the brain region. In primary tissue cultures of pure chicken neurones and glia, gamma-hydroxybutyric acid binding occurs exclusively in the neuronal preparations.

Animals↗
PubMed1982

Circadian variations of noradrenaline, 5-hydroxytryptamine and dopamine in specific brain areas of C57Bl/6 and BALB/c mice.

Daily variations in noradrenaline, 5-hydroxytryptamine and dopamine turnover were evident in two strains of mice (C57Bl/6 and BALB/c) subjected to 12-12 h light-dark cycles. These fluctuations were also evident under continuous light (L-L) in C57Bl/6 mice only, a strain which is characterized by clear-cut circadian wheel running activity in the absence of external synchronizers.

Animals↗
PubMed1982

Modifications in energy metabolism during the development of chick glial cells and neurons in culture.

Developmental changes in lactate dehydrogenase (LDH), enolase, hexokinase (HK), malate dehydrogenase (MDH), and glutamate dehydrogenase (GDH) activities were measured in cultures of pure neurons and glial cells prepared from brains of chick embryos (8 day-old for neurons, 14 day-old for glial cells) as a function of cellular development with time in culture. The modifications observed in culture were compared to those measured in brain extracts during the development of the nervous tissue in the chick embryo and during the post-hatching period. A significant increase of MDH, GDH, LDH, and enolase activities are observed in neurons between 3 and 6 days of culture, whereas simultaneously a decrease of HK values occurs. In the embryonic brain between 11 and 14 days of incubation, which would correspond for the neuronal cultures to day 3 through 6, modifications of MDH, GDH, HK, and enolase levels are similar to those observed in neurons in culture. Only the increase of LDH activity is less pronounced in vivo than in cultivated cells. The evolution of the tested enzymatic activities in the brain of the chick during the period between 7 days before and 10 days after hatching is quite similar to that observed in cultivated glial cells (prepared from 14 day-old embryos) between 6 and 18 days of culture. All tested activities increased in comparable proportions. The modifications of the enzymatic profile indicate that some maturation phenomena affecting energy metabolism of neuronal and glial elements in culture, are quite similar to those occuring in the total nervous tissue. A relationship between the development of the energy metabolism of the brain and differentiation processes affecting neuroblasts and the glial-forming cells is discussed.

Animals↗
PubMed1982

Ontogeny and distribution of specific succinic semialdehyde reductase apoenzyme in the rat brain.

The ontogeny and distribution in rat brain of specific succinic semialdehyde reductase is described. This enzyme is probably responsible for the synthesis of gamma-hydroxybutyrate in brain. The highest activities and levels of apoenzyme are found in cerebellum, olfactory bulb, septum and median hypothalamus. During neonatal development, the enzyme activity remains stable at least until 63 days of age. As the levels of other enzymes of the GABA shunt pathway increase during this same period, this result indicates that there is a relative decrease in the reductive pathway of succinic semialdehyde catabolism during development leading to gamma-hydroxybutyrate synthesis, compared to the oxidative pathway leading to succinate.

Animals↗
PubMed1982

Effect of hydrocortisone and thyroxine on ATPase activities of neuronal and glial cell lines in culture.

The effect of hydrocortisone and thyroxine, on the activities of Ca2+- and Mg2+- ATPase was studied in cultured neuronal (clone M1) and glial (clones NN and C6) cell lines. For M1 and NN cells an increase in Ca2+- and Mg2+-ecto-ATPase activity was found when the cells were cultured during 4-6 days in presence of hydrocortisone or together with thyroxine. In the same conditions, a decrease in Ca2+- and Mg2+-ecto-ATPase activity was found for the C6 cells. In C6 cells the effect of hormones was more pronounced for the Mg2+- than for the Ca2+-ecto-ATPase activity. The observed decrease may be related to the tumoral origin of the C6 cells. The activity of (Na+, K+)-ATPase in all three cell lines increased in presence of hydrocortisone or together with thyroxine when the cells were cultured during 4-6 days, in presence of the hormones, whereas the total Mg2+- ATPase activity increased only after 6 days of treatment. Thyroxine alone has very few effect either on Ca2+- and Mg2+-ecto-ATPase, or on (Na+, K+)- and total Mg2+-ATPase activity. These observations are interpreted to indicate that hormones may modulate or induce enzymatic activities involved in active transport phenomena in nervous tissue.

Adenosine Triphosphatases↗
PubMed1982

Gangliosides in various brain areas of three inbred strains of mice.

The ganglioside patterns of cerebellum, cortex, pons-medulla, hypothalamus, hippocampus and caudate nucleus of three inbred strains of mice (C57BL/6J, DBA/2J and BALB/cJ) have been analysed. All brain areas contained both the simple and complex species of gangliosides. GD1a was the major ganglioside in cortex, hippocampus and caudate nucleus whereas GT1b was the major species in cerebellum, hypothalamus and pons-medulla. In hippocampus, the percentages of GT1b and GD1a were quite similar. Pons and medulla exhibited the highest levels of GM1 (which approaches the value of GT1b) and the lowest values of GD1a. A ganglioside, which was present in highest amounts in cerebellum disappeared after alkali treatment. Highly significant differences were observed in the amounts and patterns of gangliosides among brain areas of the three strains. Highly significant differences (p less than 0.001) were also found in the ganglioside distribution of various brain areas among the strains, especially for tri- and tetrasialogangliosides between Balb and DBA. A significant difference of GM1 was observed in the cerebellum when comparing DBA with the two other strains. It is likely that the differences might be related to their relative abundances in certain cell types and for defining synaptic circuits in brain areas of some strains.

Animals↗
PubMed1982

Anticonvulsant and antiaggressive properties of di-n-propyl acetate after repeated treatment.

Swiss albino mice were treated twice daily with 200 mg/kg (i.p.) di-n-propylacetate (DPA), for 14 days and sacrificed 15 hr after the last injection, with or without an additional injection of 400 mg/kg at 45 min before death. Without the additional injection, the brain distribution of GABA followed closely that of control mice; with the additional injection, the pattern of regional increase of brain GABA was very similar to that following an acute injection of DPA. The anticonvulsant and antiaggressive properties of DPA were similar in rodents treated acutely or additionally after repeated DPA treatment. Neither the anticonvulsant nor the antiaggressive properties could be observed 15 hr after the last of the repeated injections of DPA. A residual effect of DPA against seizures induced by pentetrazole was shown, i.e. a potentiation of the anticonvulsant properties of the second of two successive injections of DPA, the latter being given after the decrease of the GABA levels in whole brain to control values.

Acoustic Stimulation↗
PubMed1982

gamma-Aminobutyric acid in brain areas of isolated aggressive or non-aggressive inbred strains of mice.

In order to investigate the effects of social isolation on aggressive behavior and GABA levels in different brain areas, inbred mice of the C57 Bl/6 and the DBA/2 strains were housed individually over a period of 8 weeks. Social isolation induced a clear increase of aggressive responses only in the DBA/2 strain and a decrease of GABA levels in septum, striatum, olfactory bulb and posterior colliculus in both the C57Bl/6 and in the DBA/2 strains. An increase of neurotransmitter concentration was observed in amygdala of DBA mice. DBA mice when compared to C57 mice showed significantly lower levels of GABA in olfactory bulb and striatum. These results are discussed in light of several previous studies which have pointed out a correlation between a deficiency of GABA mediated inhibition in some brain areas and different kinds of aggressive behavior as well as the possibility of a blockade of aggressive behavior by potentiation of GABAergic mediated inhibition. A possible suggestion emerging from our results is that the aggressive responses exhibited by isolated DBA mice but not by isolated C57 mice may be related to lower levels of the inhibitory neurotransmitter in the olfactory bulb and striatum.

Aggression↗
PubMed1982

Effect of valproic acid on brain serotonin metabolism in isolated and grouped rats.

The effect of the GABA transaminase inhibitor valproic acid (DPA) on serotonin (5HT) metabolism of different brain regions were studied in both grouped and isolated rats. One hour after DPA injection 5HT levels in the amygdala were increased in grouped and isolated rats. In the hypothalamus of grouped rats, changes in 5HT metabolism were also found. The alteration in 5HT metabolism in grouped rats was reversed 150 min after injection of DPA. At this same time, a large and significant increase in 5HT turnover was observed in all brain areas examined in isolated rats. It can be concluded that prolonged isolation induces a differential sensitivity to the effects of DPA leading to differences in 5HT metabolism: the drug effect being more intense in isolated rats.

Animals↗
PubMed1982

Effects of opiate antagonists on social and aggressive behavior of isolated mice.

Opiate antagonists naloxone (1 and 1.5 mg/kg IP) and naltrexone (2.5 and 5 mg/kg IP) inhibit aggressive responses of DBA/2 isolated mice, while increasing the duration of some social activities such as sniff-body, sniff-nose and following. At the doses employed naloxone and naltrexone did not affect motor activity and self-grooming of paired mice. These findings are discussed in terms of the endogenous opioids system involvement in arousability, in the response of the organism to stressful events, in the motivational mechanisms which control social behavior and in the functioning of some neurotransmitter systems which are known to play an important role in the control of isolation-induced aggressive behavior.

Aggression↗
PubMed1982

Regional distribution of superoxide dismutase in rat brain during postnatal development.

Superoxide dismutase in nervous system protects readily oxidizable compounds such as catecholamines against toxic effects of oxygen. We investigated superoxide dismutase activity during development in 5 brain regions selected for a wide range of catecholamine concentration and turnover: cerebellum, neocortex, striatum, hypothalamus and medulla-pons. The cytosolic and the particulate enzyme were measured from birth to 6 months of age. In cerebellum the cytosolic enzyme shows considerable activity on the first postnatal days; the particulate enzyme is less active, both reach a maximum at 3 months. In cortex and striatum both activities were low during the postnatal days and reach a plateau at 3 months. In hypothalamus both activities are higher during the postnatal days and reach a maximum at 3 months. In medulla-pons the values are 2 times higher than in all other regions; the cytosolic enzyme reaches a maximum at 2 months whereas the particulate enzyme reaches a plateau at 3 months. Thus our results show an increase of superoxide dismutase activity during development in all brain regions; the highest activities were found in regions with high catecholamine content.

Aging↗
PubMed1982

Neuron-specific and non-neuronal enolase in developing chick brain and primary cultures of chick neurons.

Developmental changes of the neuron-specific enolase (NSE) and the non-neuronal enolase (NNE) were determined in pure neuronal, or mixed cultures of neuronal and glial cells, prepared from brains of 8-day-old chick embryos, as a function of cellular development with time in culture. The modifications observed in culture were compared to those measured in brain during the development of the nervous tissue in the embryo and during the post-hatching period. In the whole brain, the total enolase activity increases progressively until the adult level, the NSE appears only 4 days before hatching. The total enolase activity of pure neurons increases until 8 days of culture but the NSE never appears during this period. Mixed cultures of neurons and glial cells present an increase of total activity until 14 days of culture and neuron-specific form of the enzyme can be observed after 6 days of culture. Our results suggest that NSE appears only in the functional brain and is expressed in cultivated neurons only when glial cells are present simultaneously.

Animals↗
PubMed1982

Sodium valproate: kinetic profile and effects on GABA levels in various brain areas of the rat.

1. The kinetic profile of sodium valproate (VPA) and the GABA levels were studied in discrete brain areas of the rat after an i.p. injection of 200 mg/kg. The results were discussed comparatively with GABA-T and GAD activities reported in the literature. 2. VPA was rapidly distributed in brain areas; its concentrations, its kinetic parameters and the GABA levels after the drug administration were not uniform in the different brain areas studied. 3. The results showed a particular relation of the VPA to the olfactory bulbs; in this specific area the VPA effect on GABA level was stronger; the VPA apparent half life of elimination was longest; the VPA apparent disappearance rate constant was smallest; the initial GABA level was higher; the activities of GABA-T and GAD were higher than in other brain areas studied except the hypothalamus. 4. These data were correlated with the role of the olfactory bulbs in the behaviour of the rodents.

Animals↗