Harald Rösner

A functional model of sialo-glyco-macromolecules in synaptic transmission and memory formation.

A concept is presented of the molecular involvement of sialo-glyco-macromolecules in the processes of synaptic transmission and memory formation. The main point of the concept is the assumption that by complexation between lipid-bound negative charged sialic acid and Ca 2+ -ions the synaptic membrane is “closed”, while dissociation of these complexes will cause an “opening” of presynaptic regions. The synaptic zones of contact are assumed to become functionable during ontogenesis, only after the incorporation of sialyl residues into the carbohydrate coat of neuronal membrane. Additional accretion of sialo-glyco-macromolecules at the contact zones, could be the molecular basis for a facilitation of defined neural pathways, which might be the morphological correlate of an engram. Published experimental data are used as evidence for the validity of this concept.

Chapter 10 Ca2+-Ganglioside-interaction in neuronal differentiation and development

Publisher Summary On the basis of the well-known functional properties of calcium for cellular homeostasis and of the peculiar physico-chemical properties of gangliosides in general, this chapter reviews investigations of basic interactive properties of gangliosides with respect to calcium and with functional membrane-bound proteins as fundamentals for the understanding of the role of gangliosides in differentiation and development. In this regard, experimental data are presented in the chapter concerning (1) the ultrastructural localization of calcium, a calcium pump (high-affinity Ca 2+ -ATPase) and of gangliosides in nerve fiber terminals, (2) the effect of exogenous gangliosides on Ca 2+ -deprived cultured neurons, and (3) calcium–ganglioside–peptide interactions in artificial mono- and bilayer systems. The ultrastructural data concerning the localization of calcium, of a high-affinity calcium ATPase (calcium pump), and of poly-sialoganglioside epitopes in close vicinity of the very local zone of contact within synaptic terminals are in good agreement with the physico-chemical results and recent biochemical data dealing with activatory effects of neuronal protein phosphorylation and ATPases by exogenous gangliosides.

Brain gangliosides and temperature adaptation in eury- and stenothermic teleost fish (carp and rainbow trout)

1. 1.|The brain ganglioside pattern of eurythermic carp (Cyprinus carpio) and stenothermic rainbow trout (Salmo gairdneri) was investigated by means of biochemical methods under experimentally induced temperature changes (acclimination), and seasonal temperature fluctuations (acclimatization). 2. 2.|In both species during the process of thermal adaptation to lowered environmental temperatures, changes in the brain gangliosides could be registered resulting in a more polar pattern. 3. 3.|While in carp this “polysialization” was indicated by a decrease of all oligosialogangliosides in favour of more polar fractions; in rainbow trout a more differentiated change of the pattern occurred characterized by a significant decrease (∼ 60%) in the concentration of the monosialoganglioside GM3. 4. 4.|The results are discussed with respect to a possible involvement of neuronal gangliosides in the mechanism of thermal adaptation of poikilothermic animals to changes in the environmental temperatures.

Changes in the contents of gangliosides and glycoproteins and in the ganglioside pattern of the chicken brain

THE CONCENTRATION of N-acetylneuraminic acid (NeuNAc) was found to increase throughout development in the prenatal chicken brain (GRAY & IRWIN, 1973; SCHENGRUND & ROSENBERG, 1971) and the rat brain (HOLIAN et al., 1971; SUZUKI, 1965). In addition the ganglioside patterns of the rat and human brain (SUZUKI, 1965; VANLER et al., 1971) and the embryonic chicken brain (SCHENGRUND & ROSENBERG, 1971) were found to change during development. Corresponding data for the chicken brain, at the time immediately around the hatching and post-hatching stages are however still lacking. We therefore measured the content of gangliosideand glycoprotein-bound NeuNAc in different areas of the chicken brain during development and also determined the ganglioside pattern.

Chemotaxonomical investigations on the occurrence of sialic acids in protostomia and deuterostomia

Abstract Several tissues of different protostome species were tested in respect to the occurence of sialic acid. There is no sialic acid in the turbellarian Euplanaria gonocephala and the mollusc Helix pomatia . In contrast to other tissues the digestive gland of the decapod crustaceans Astacus leptodactylus and Uca tangeri contains 60–80 μg of sialic acid per gram wet weight. Radioactive tracer experiments showed that Astacus leptodactylus cannot synthesize sialic acid by using the specific precursor N -acetyl-mannosamine but obviously resorbs exogenous sialic acid taken up with the food and stores it in the digestive gland. It is suggested that protostomes in general are devoid of endogenous sialic acid whereas it is abundant in deuterostomes. Contradictory to existing results low amounts of a resorcinol positive substance, probably a sialic acid, were detected in the deuterostome tunicate Phallusia mammilata .

Possible involvement of polysialogangliosides in nerve sprouting and cell contact formation: an ultracytochemical in vitro study

Abstract: In Cichlid fish (Oreochromis mossambicus) primary cell cultures from whole brain and optic tectum, the differentiation‐dependent distribution of polysialogangliosides on the outer cell surface has been followed on an ultrastructural level. For this, a two‐step labeling technique with the monoclonal mouse antibody Q211, recognizing a polysialoganglioside‐associated epitope, followed by a secondary IgM antibody, coupled to colloidal gold sols as an electron‐dense marker, has been used. The gold grains are not uniformly distributed over the whole cell surface, but rather are clearly arranged clusters. In cells from freshly hatched larvae, both cell bodies and nerve fibers strongly exhibit the polysialoganglioside epitope on their surface. With progressing development, neuronal cell labeling is more and more restricted to nerve fibers and especially to cellular adhesion zones, including synaptic terminals, thus suggesting a functional involvement of polysialogangliosides in nerve sprouting and initiation of both cell‐to‐extracellular matrix and cell‐to‐cell contacts.

Phylogenetic recapitulation of brain ganglioside composition during ontogenetic development

Abstract 1. 1. Brain gangliosides of representatives belonging to four vertebrate classes (elasmobranch fish, reptile, bird and mammal) have been investigated with respect to a recapitulation of ganglioside biosynthesis during ontogenetical development in comparison to phylogeny. 2. 2. During phylogeny and early ontogeny of higher vertebrates the number of ganglioside fractions is reduced especially with regard to more polar ganglioside species. 3. 3. Arranging the different ganglioside fractions subsequent to their three pathways of biosynthesis, it becomes apparent that in elasmobranch fish and in embryonic chicken the third (“C”) pathway of ganglioside synthesis (G M3 , G D3 , G T3 , G T2 , G T1c , G Q1c , G P1 ) is used, whereas in the adult chicken there is a preponderance of the first and second (“A” and “B”) way (G M2 , G M1 , G D1a and G D2 , G D1b , G T1b , G Q1b ). 4. 4. The parallel reduction of the C-pathway for ganglioside biosynthesis during phylogeny from elasmobranch fish to birds and mammals respectively and during ontogeny in high vertebrates is taken as evidence for a further verification of the recapitulation principle according to Haeckels biogenetic rule.

Temperature effects on the incorporation of sialic acid into gangliosides and glycoproteins of fish brain

1. 1.|Temperature effects on the in vivo-incorporation of N-[3H] acetylmannosamine into brain gangliosides and sialoglycoproteins as well as of [3H] leucine into brain proteins were investigated in goldfish (Carassius auratus) under different incorporation- (Intracranial or intra-ocular injections) and acclimation-conditions. 2. 2.|The incorporation of [3H] leucine into proteins was slightly reduced at 7°C in comparison to 20°C-conditions. 3. 3.|The radioactive NeuAc-labelling of glyproteins was reduced to about one-half and that of gangliosides to as little as one-fifth at the lower temperature. Concommittantly, at 7°C higher amounts of non-incorporated low molecular label occurred compared with the amount found at 20°C. 4. 4.|Due to the decreased incorporation of label and an additional diminishing effect of the lowered temperature on the rapid axonal transport, the renewal of gangliosides in the nerve endings of the optic tract was negligible at 7°C. 5. 5.|Pattern analysis showed that the inhibitory effect of lowered environmental temperatures on the brain ganglioside metabolism was even more pronounced in the poly-sialogangliosides compared with their less sialisated homologues.

Effects of Neonatal 6-Hydroxydopamine Treatment on Cortical Development in Mice and Rats as Monitored by Developmental Changes of Gangliosides

In a comparative study newborn rats and mice received subcutaneous (s.c.) injections of 6-hydroxydopamine (6-OHDA: 100 mg/kg) on postnatal days (p.d.) 1-3. In rats the treatment permanently reduced synaptosomal 3H-noradrenaline (3H-NA) uptake in the cortex to about 50-60% of control values. Conversely, cortical 3H-NA uptake was only temporarily reduced in treated mice during the first week and central noradrenergic neurons completely recovered during the second and third week. The different response of mice and rats to 6-OHDA is suggested to be due to earlier maturation of the noradrenergic system in mice, making it less vulnerable to neonatal injections of the neurotoxin. To determine whether the development of the cortex would be altered after degeneration of its noradrenergic innervation, developmental changes of cortical ganglioside content and composition of 6-OHDA-treated animals were compared to that of littermate controls. In 18-day-old rats, where reduction of 3H-NA uptake had persisted, ganglioside content was reduced by 16.5%, indicating growth impairment of neuronal membrane structures. Cortical gangliosides of younger rats and all the stages studied in mice were not affected by 6-OHDA treatment.

Changes of brain gangliosides in chicken and mice during heterothermic development

Abstract Developmental profiles of brain gangliosides of chicken and mice were correlated to thermo-biological parameters. In parallel with an increasing body temperature and resistance to cold stress (within the first 11 postnatal days) the brain gangliosides change to a less polar pattern, indicated by a higher proportion of oligosialogangliosides.