Effect of exogenous gangliosides on nerve cell regeneration?
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Biomedical subjects
Publications and source records attributed to H Rahmann.
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The effect of exogenous neuraminidase on spontaneous and evoked synaptic activity was investigated following injection of the enzyme into frog spinal cord and into cord and into the carp optic tectum. 1. Injection of enzyme into spinal cord segments caused a significant increase of motoneuron activity in the corresponding spinal nerve, which lasted for 7--31 min. 2. The amplitude of postsynaptic evoked potentials in the optic tectum was increased after neuraminidase injection up to 200% of control level for 20--40 min, whereas the amplitude of summed action potentials of retino-tectal afferents remained unchanged. 3. Similar effects were observed in single cell responses of the optic tectum with some differences in the degree of increase in activity, as well as latency and final depression of the stimulus response. 4. The extent of neuraminic acid liberation following neuraminidase treatment was determined biochemically. In both tissues investigated the amount of free neuraminic acid was increased significantly (4--5.5 fold) after enzyme treatment. Whereas after enzyme injection into spinal cord and optic tectum the percentage release of total glycoprotein- and glycolipidbound neuraminic acid was 12% and 15%, respectively, liberation from enzyme incubated tissue homogenates was somewhat higher (20.5% and 24%).
1. Brain ganglioside patterns of normothermic and hibernating golden hamsters (Mesocricetus auratus) and laboratory mice had been investigated. 2. The ganglioside pattern of normothermic golden hamsters in comparison to that of mice is characterized by an unusual high amount of the polar trisialoganglioside GT1. 3. In the hibernating golden hamster in contrast to normothermic counterparts the brain gangliosides are more polar (polysialization-effect). 4. The results are discussed with regard to the hypothesis that neuronal membranes provided with more polar gangliosides at lower environmental temperatures might be more efficient with respect to the high complexation ability of gangliosides with Ca2+-ions.
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The binding of d-tubocurarine by ganglioside mixtures from chicken and bovine brain as well as by the single gangliosides GGtet1-NeuAc, GGtet2aNeuAc and GGtet3aNeuAc was demonstrated by means of equilibrium gel filtration. The sialyl-oligosaccharide derivatives of GGtet1NeuAc and GGtet2aNeuAc, however, did not bind any d-tubocurarine. A lack of binding was also found for the gangliotetraosyl-ceramide GgOse4Cer, free NeuAc, mucin and sphingomyelin. Under saturation conditions, GGtet1NeuAc bound 0.58, GGtet2aNeuAc 0.92 and GGtet3a-NeuAc 1.23 mol d-tubocurarine per mol ganglioside. Half-maximal binding was achieved between 1 and 1.5 x 10(-5)M d-tubocurarine. Ca2 was found to inhibit the binding of d-tubocurarine to gangliosides (50% at 4 x 10(-4)M Ca2). Mg2 was about 4 times less effective. Acetylcholine caused a 40% inhibition at 4 x 10(-3)M, whereas K and Na had only slight effects even at 5 x 10(-2)M.
The binding of Ca2 to single ganglioside species (GGtet1NeuAc, GGtet2aNeuAc, GGtet 3aNeuAc), to their free, reducing sialyl-oligosaccharides and to ganglioside mixtures from chicken brain was investigated by means of ion-sensitive electrodes (potentiometry). Unlike the sialyl-oligosaccharides and free N-acetylneuraminic acid, gangliosides were found to possess two different modes of binding for Ca2, depending on the total concentration of Ca2. This was mainly indicated by a release of up to 75% of previously bound Ca2 after raising the total Ca2-concentration above a critical level of about 5--9 X 10(-5)M. Addition of acetylcholin (9mM), Li, K, and Na, respectively, caused a release of Ca2 from ganglioside-Ca2-complexes (0.1mM Ca2, 0.1mM ganglioside-NeuAc) in the sequence: acetylcholin : Li : K : Na = 4 : 3 : 1 : 1 composed on molar basis (9mM).
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Gangliosides, which are highly enriched in synaptic membranes, show great differences in concentration and pattern constellation as well during early ontogenetical development as on interspecies level in vertebrates. As, up to now, there is no reasonable explanation for these findings, and as it is assumed the synapse to be the primary site of thermal adaptation, the attempt was made to investigate whether there are any correlations between brain gangliosides and the thermal adaptation phenomenon. 1. While in the brains of adult homeothermic vertebrates (with thermo-regulation: mammals, birds) the di-sialoganglioside GD1a predominates, in the brain of poikilotherms (without thermo-regulation: e.g. amphibia, teleost fishes) more polar polysialogangliosides are present. 2. In homeotherms during their early perinatal phase (heterothermic phase: thermor-regulation being not yet developed) a temporary poly-sialisation of brain-gangliosides occurs. 3. In poikilotherms, during the process of thermal adaptation to lowered environmental temperatures, a poly-sialisation of brain gangliosides can be observed, as well during the phase of acclimatization (adaptation to seasonal changes in temperature) as also to acclimation (experimentally induced changes in the environmental temperature). 4. The phenomenon of poly-sialisation of brain gangliosides during adaptation to lowered environmental temperatures can be correlated with changes in some behavioral (e.g. motorical activity) and electrophysiological parameters. 5. On the background of a general hypothesis on the involvement of gangliosides in the process of transmission [23, 24], a functional model on the participation of gangliosides in the process of thermal adaptation is discussed with special regard to the formation of Ca++-ganglioside-complexes, which are highly sensitive to temperature changes.
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Unilateral stimulation of the lateral-line organ (LLO) of the teleost Scardinius erythrophthalmus by current water caused an increase in the afferent fibre activity in the stimulated organ of about 3.5 times as compared with the non-stimulated LLO. There was an increase of [3H] histidine incorporation as compared to controls following stimulation applied either at the beginning (1 h) or at the end (1.5-6 h) of various incorporation times. Following a 1 h stimulation period, the different areas of the LLO-system (lateral nerve, medulla oblongata, cerebellum and valvulae cerebelli), as well as the optic tectum, subtectum and spinal cord showed a significant increase of protein labelling; whereas after 12 h post-incorporation times only the lateral nerve showed highly significant differences as compared to controls. In animals stimulated at the end of a 12 h pre-incorporation period (1.5-6 h) there was a significant increase of protein labelling in all investigated structures of the brain as compared to controls.
The brain ganglioside pattern of taxonomically close and distant related fish living at different temperatures were compared with the mammalian pattern. Furthermore the goldfish brain pattern was investigated after adaption (acclimitization, acclimation) to different temperatures. The results demonstrate correlations between body temperature and brain gangliosides: the lower the body temperature of animals, the higher the relative proportion of multi-sialo-gangliosides. The results are discussed with respect to the possible functional role of Ca++-ganglioside-complexes for the process of synaptic transmission.
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By means of histochemical experiments the qualitative (microphotographs) and quantitative (cytophotometry) distribution of sialic acid containing compounds was investigated in the mesencephalon and cerebellum of Carassius carassius. 1. The perikarya of nerve cells are especially stained by means of Azur A. 2. Nerve fibres, on the other hand, showed positive reactions with colloidal ironhydroxyd (CIH). 3. In different structures of the CNS the intensity of CIH-staining is decreased up to about 55% following treatment with neuraminidase. 4. There are no differences in the reactions of 7 degrees C as compared to 20 degrees C adapted animals.
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