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L Hertz

Publications and source records attributed to L Hertz.

At least 91 records · Page 5Linked to original sources
PubMed1992

Astrocyte maturation and susceptibility to ischaemia or substrate deprivation.

We demonstrate that immature astrocytes die much earlier than mature astrocytes when substrate is deprived in the presence of oxygen. In contrast, mature astrocytes die much earlier than immature astrocytes when substrate is deprived in the absence of oxygen. These observations correlate well with the recent findings that the newborn rodent brain is more susceptible to damage from lack of substrate than from lack of oxygen. The basis for this susceptibility of immature astrocytes to substrate deprivation in the presence of oxygen is not clear, but perhaps is related to the ability of the cell to scavenge free radicals.

Animals↗
PubMed1992

Ions, water, and energy in brain cells: a synopsis of interrelations.

A brief summary is given of some of the key points of the individual contributions at this International Brain Research Organization satellite meeting, presenting up-to-date, expert knowledge of energy metabolism, ionic turnover, and cell swelling at the cellular level of the mammalian central nervous system. On the basis of this material, we are also suggesting a unified concept of reciprocal interactions between metabolism, ion carriers, and ion channels, which are of crucial importance for the function of the central nervous system.

Animals↗
PubMed1992

Energy metabolism at the cellular level of the CNS.

Evidence is accumulating that interactions between different cell types are of paramount importance for CNS function, for example, release of the excitatory transmitter glutamate from neurons and its preferential uptake into astrocytes. Some information is also available about energy metabolism in different cell types, or more often in models of different cell types (e.g., synaptosomes, cultured neurons, cultured astrocytes). In this review an attempt is made not only to correlate information obtained with different cell models but also to integrate this information with in vivo data, with histochemical observations, and with results obtained using brain slices. The emerging patterns indicate that neurons, synaptosomes, and astrocytes are all capable of complete glycolysis and oxidation of glucose. Elevated extracellular concentrations of potassium, known to occur in vivo, enhance energy metabolism by mechanisms that differ between neurons and astrocytes and to a large extent serve to reaccumulate extracellular potassium ions into adjacent cells. Monoaminergic agonists also stimulate energy metabolism, but mainly or exclusively in astrocytes. Profound differences are found between the effects of excess potassium and of aminergic transmitters, suggesting that high potassium concentrations enhance neuronal-astrocytic interactions, whereas the monoamines may tend to dissociate metabolic events in neurons and in astrocytes.

Animals↗
PubMed1992

Use of cell cultures to differentiate among effects of various ischemia factors on astrocytic cell volume.

Mouse astrocytes were subjected to in vitro models of ischemia (hypoxia with or without substrate deprivation, excess potassium, or elevated glutamate). Three hours of hypoxia alone or with substrate deprivation had little effect upon the morphology of astrocytes but did cause disaggregation of polyribosomes. Excess (12-50 mM) potassium added (as KCl) to a normal isotonic medium also caused no swelling; it did, however, cause a shrinkage of cell volume. When 50 mM potassium was substituted for a similar amount of sodium, marked swelling occurred. Swelling of astrocytes was also seen after addition of glutamate (50 microM to 1 mM) to the culture medium. These results show that ischemia per se does not result in astrocytic swelling; rather, microenvironmental alterations such as rising glutamate levels and changes in the sodium/potassium ratios result in astrocytic swelling. We conclude that one can use astrocytes in culture to dissect out the mechanisms that cause postischemic alterations in astrocytes in vivo.

Animals↗
PubMed1992

Effect of vasopressin on brain swelling at the cellular level: do astrocytes exhibit a furosemide--vasopressin-sensitive mechanism for volume regulation?

Two sets of new observations are reported: (i) astrocytes in primary cultures show an increased potassium-induced swelling in the presence of 1-100 x 10(-12) M vasopressin, whereas no similar phenomenon is found in primary cultures of neurons, and (ii) the furosemide-sensitive cotransport system for uptake of K+, Na+, and Cl-, which is known to exist in astrocytes, is absent in neurons. On the basis of these findings and observations by other investigators on transport of ions and water in the brain in vivo, a novel mechanism is suggested, according to which all boundaries of brain parenchymal tissue (perivascular astrocytic end-feet, glia limitans, and ependyma) in the absence of vasopressin are capable of performing a net uptake of K+, Na+, and Cl- without uptake of water, and that the resulting hyperosmolarity in the presence of vasopressin leads to water uptake (cell swelling), which causes a reduction in the amount of water in the interstitial fluid and thus an increase in extracellular concentrations of ions.

Animals↗
PubMed1991

Differences in transmitter release, morphology, and ischemia-induced cell injury between cerebellar granule cell cultures developing in the presence and in the absence of a depolarizing potassium concentration.

Release of glutamate and aspartate was measured in mouse cerebellar granule cells in primary cultures grown for 4-16 days in serum-containing tissue culture medium with either a partially depolarizing (25 mM) or a physiological concentration of potassium (5.4 mM). The cells migrated to form aggregates connected by a network of processes during the first week in culture and both groups of cultures survived for at least 2 weeks. In cultures grown in the presence of 25 mM potassium for at least 8 days there was a large (approximately 10 nmol/min/mg protein), calcium-dependent glutamate release and a smaller aspartate release during superfusion with 50 mM potassium. This response was not present in cultures grown in the physiological medium. Nevertheless, exposure to an elevated potassium concentration caused a normal, or even enhanced calcium entry into the cells. Phase contrast microscopy showed a similar appearance of the cellular aggregates under each of the two conditions. Electron microscopy revealed that the aggregates consisted of a centrally located neuropil and peripherally located granule cell bodies. The morphology of the cell bodies and the neuropil in the cells grown at the high potassium concentration closely resembled that of cerebellar granule cells in vivo. In the cells grown at the low potassium concentration, cell bodies, axons and synaptic vesicles looked normal, but the remainder of the neuropil, especially dendrites, showed massive degeneration. Immunochemical measurements demonstrated similar amounts of synaptophysin under each of the two culturing conditions, thus confirming our impression that there were similar numbers of synaptic vesicles and hence presynaptic elements in the two types of cultures. Fluorescence microscopy, using fluorescein diacetate to stain living cells and propidium iodide to stain dead cells, indicated a much greater resistance to ischemic cell injury in the cells cultured at the low potassium concentration. Possible reasons for this difference are discussed.

Animals↗
PubMed1991

Stimulation of energy metabolism by alpha-adrenergic agonists in primary cultures of astrocytes.

Noradrenaline effects on glucose oxidation were studied in primary cultures of astrocytes. CO2 formation from labeled glucose was enhanced in the presence of noradrenaline. The stimulatory effect by noradrenaline was exerted both on lactate formation (approximately 20%) and on tricarboxylic acid activity (CO2 production from glutamate) (approximately 40%). The effect was, at least partly, exerted on the alpha-ketoglutarate dehydrogenase step. The EC50 value for noradrenaline on lactate formation was significantly lower (60 nM) than that on oxidative metabolism (1,900 nM). Studies with specific adrenergic agonists and antagonists showed that various receptor subtypes are involved. Thus, the effect on lactate formation was mediated exclusively by stimulation of an alpha 1 receptor whereas oxidative metabolism was enhanced by both alpha 1 and alpha 2 receptor stimulation. No effects were exerted by beta receptor agonists or antagonists.

Adrenergic alpha-Agonists↗
PubMed1991

Establishment of highly enriched type-2 astrocyte cultures and quantitative determination of intense glutamine synthetase activity in these cells.

We report procedures that allow one to develop and maintain cultures highly enriched in rat neopallial type-2 astrocytes. Even after four weeks such cultures consist of more than 90% type-2 astrocytes, approximately 5% O-2A progenitors and fewer than 2% type-1 astrocytes. Their survival for more than 5 days requires the addition of conditioned medium from type-1 astrocyte cultures. The type-2 astrocytes have an intense glutamine synthetase activity whose basal level is sevenfold higher than in type-1 astrocytes. The glutamine synthetase activities of both the type-2 and type-1 astrocytes are increased after exposure to cortisol. Thus, type-2 astrocytes express the two quint-essential astrocytic features: glial fibrillary acidic protein (previously reported by others) and glutamine synthetase.

Animals↗
PubMed1991

Utilization of alpha-ketoglutarate as a precursor for transmitter glutamate in cultured cerebellar granule cells.

Alpha-ketoglutarate together with an amino group donor (alanine) was shown to be able to serve as a precursor for the glutamate pool which is released by potassium-induced depolarization (i.e., transmitter glutamate) in cerebellar granule cells. However, these compounds could not be utilized as precursors for intracellular glutamate or for release of transmitter aspartate. The formation of transmitter glutamate was inhibited by the transamination inhibitor aminooxyacetic acid but not by phenylsuccinate, an inhibitor of the dicarboxylate carrier in the mitochondrial membrane. Both of these inhibitors have previously been found to inhibit synthesis of transmitter glutamate from glutamine. The results support the hypothesis that alpha-ketoglutarate and alanine undergo transmination in the cytosol to form pyruvate and glutamate, and that this glutamate pool is available for transmitter release of glutamate but does not constitute the major intracellular pool of glutamate.

Alanine↗
PubMed1991

Effects of potassium on the anion and cation contents of primary cultures of mouse astrocytes and neurons.

In astrocytes, as [K+]o was increased from 1.2 to 10 mM, [K+]i and [Cl-]i were increased, whereas [Na+]i was decreased. As [K+]o was increased from 10 to 60 mM, intracellular concentration of these three ions showed no significant change. When [K+]o was increased from 60 to 122 mM, an increase in [K+]i and [Cl-]i and a decrease in [Na+]i were observed. In neurons, as [K+]o was increased from 1.2 to 2.8 mM, [Na+]i and [Cl-]i were decreased, whereas [K+]i was increased. As [K+]o was increased from 2.8 to 30 mM, [K+]i, [Na+]i and [Cl-]i showed no significant change. When [K+]o was increased from 30 to 122 mM, [K+]i and [Cl-]i were increased, whereas [Na+]i was decreased. In astrocytes, pHi increased when [K+]o was increased. In neurons, there was a biphasic change in pHi. In lower [K+]o (1.2-2.8 mM) pHi decreased as [K+]o increased, whereas in higher [K+]o (2.8-122 mM) pHi was directly related to [K+]o. In both astrocytes and neurons, changes in [K+]o did not affect the extracellular water content, whereas the intracellular water content increased as the [K+]o increased. Transmembrane potential (Em) as measured with Tl-204 was inversely related to [K+]o between 1.2 and 90 mM, a ten-fold increase in [K+]o depolarized the astrocytes by about 56 mV and the neurons about 52 mV. The Em values measured with Tl-204 were close to the potassium equilibrium potential (Ek) except those in neurons at lower [K+]o. However, they were not equal to the chloride equilibrium potential (ECl) at [K+]o lower than 30 mM in both astrocytes and neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

In vitro models differentiating between direct and indirect effects of ischemia on astrocytes.

Mouse astrocytes in primary cultures were subjected to an in vitro model of ischemia (hypoxia combined with substrate deprivation, excess potassium, or elevated glutamate) and examined with the light (phase) and electron microscope. Three hours of hypoxia alone or in combination with the other insults had little effect upon the morphology of astrocytes but did cause disaggregation of polyribosomes. With reoxygenation, polyribosomes reformed and many mitochondria changed from the orthodox to the condensed configuration. Notably, there was little swelling. Excess (50 mM) potassium, added (as KCl) to a normal isotonic medium, also caused no swelling. However, when 50 mM potassium was substituted for a similar amount of sodium, marked astrocyte swelling did occur. A morphologically similar swelling was seen when glutamate (50 microM to 1 mM) was added to the culture medium, both with or without hypoxia with or without substrate deprivation. Potassium or glutamate-induced swelling was reversible with 1 h of recovery in normal medium. These results show that alterations in postischemic astrocytic morphology in vivo to a large extent can be reproduced in astrocytes in primary cultures. In addition, they suggest that postischemic astrocyte swelling is related to alterations in extracellular milieu, including accumulation of glutamate and/or alterations in the potassium/sodium ratios with increased potassium and decreased sodium. In contrast, morphologic alterations in polyribosomes and in mitochondria appear to be a direct response to ischemia itself.

Animals↗
PubMed1990

Effect of adrenergic agonists on glycogenolysis in primary cultures of astrocytes.

A stimulation of glycogenolysis in astrocytes by adrenergic agonists has repeatedly been demonstrated in the literature. However, some confusion exists regarding which type of adrenergic receptor subtype is involved, and little information is available about rates of glycogenolysis and potencies of adrenergic agonists. In the present study, we have investigated these parameters using primary cultures of mouse astrocytes which constitute a reliable model for their in vivo counterparts. Antagonists as well as agonist studies revealed that noradrenaline acts both on a beta- and on an alpha 2-receptor. Isoproterenol and clonidine, agonists acting relatively specifically on only one of these receptor subtypes could, on their own, stimulate glycogenolysis and the effect by noradrenaline could be inhibited by alprenolol (beta-adrenergic antagonist) and/or yohimbine (alpha 2-adrenergic antagonist) but not by prazosin (alpha 1-adrenergic antagonist). Excess potassium also stimulated glycogenolysis but this effect was not antagonized by adrenergic antagonists, alone or in combination. The involvement of an alpha 2-adrenergic receptor in a homogeneous culture of astrocytes provides proof that not all alpha 2-adrenergic receptors in brain are presynaptic. The maximum rate of stimulated glycogenolysis was calculated to be 3-7 nmol/min per mg protein. Computer analysis showed that the EC50 values for noradrenaline, isoproterenol and clonidine were 4.6 x 10(-8) M, 3.0 x 10(-7) M, and 6.5 x 10(-7) M, respectively.

Alprenolol↗
PubMed1990

Noradrenaline induced stimulation of oxidative metabolism in astrocytes but not in neurons in primary cultures.

Noradrenaline effects on oxidative metabolism (tricarboxylic acid cycle activity) were examined by measuring the formation of 14CO2 from labeled aspartate in primary cultures of cerebral astrocytes and neurons and of cerebellar granule cells. At all time periods studied, CO2 formation in astrocytes was significantly increased in the presence of noradrenaline. The EC50 value was calculated to be 5 x 10(-7) M. No corresponding stimulation of CO2 production in cerebellar or cortical neurons was observed, suggesting that the stimulation of energy metabolism by noradrenaline in vivo may be confined to astrocytes.

Animals↗