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PubMed1996

Synergic action of gangliosides on alpha-MSH-induced cyclic AMP levels in rat brain slices.

Gangliosides are particularly enriched in neuron cell membranes and they were postulated to be involved in the modulation of membrane-mediated transduction of information. In this study we explore the possibility that the increase in cAMP tissular levels induced by alpha-MSH may be modulated by the action of exogenously added gangliosides. We measured the level of cAMP in both tissues and medium in response to the alpha-MSH in slices previously incubated with total bovine brain gangliosides (TBG). When slices were exposed to TBG, the effect of alpha-MSH on inducing an increase in the content of cAMP was practically twice compared to the changes induced by alpha-MSH or TBG alone. We conclude that the presence of gangliosides may facilitate the alpha-MSH interaction with its receptor, increasing the cAMP levels in slices containing the CP and Acc nuclei.

Animals↗
PubMed1992

Lasting effects of postnatal hypoxia and saline injection on the striatal dopamine transport and their modification by gangliosides.

Hypobaric hypoxia (10 h daily, pO2 10 kPa) and saline administration (2.5 microliters/g body wt) from the 2nd till the 11th day of life both induced a long-lasting increase of the low-affinity dopamine (DA) uptake capacity in S1-fractions of the rat striatum. Additionally, the potassium-stimulated DA release was enhanced in adult control rats postnatally injected with saline. The administration of a mixture of bovine brain gangliosides (30 micrograms/g body wt) was found to prevent these effects. However, the kinetic constants of the DA uptake of hypoxic rats treated with gangliosides were reduced in comparison to untreated controls. Thus, the effects of gangliosides appear to differ between hypoxic and control conditions. The modification of the dopaminergic activity during brain development is discussed as a possible mechanism of the preventive effects of gangliosides against long-term cerebral dysfunctions following hypoxia or stress.

Animals↗
PubMed1993

GD3/proteosome vaccines induce consistent IgM antibodies against the ganglioside GD3.

The gangliosides of melanoma and other tumours of neuroectodermal origin are suitable targets for immune intervention with tumour vaccines. The optimal vaccines in current use contain ganglioside plus bacillus Calmette-Guérin and induce considerable morbidity. We have screened a variety of new adjuvants in the mouse, and describe one antigen-delivery system, proteosomes, which is especially effective. Highly hydrophobic Neisserial outer membrane proteins (OMP) form multimolecular liposome-like vesicular structures termed proteosomes which can readily incorporate amphiphilic molecules such as GD3 ganglioside. The optimal GD3/proteosome vaccine formulation for induction of GD3 antibodies in the mouse is determined. Interestingly, the use of potent immunological adjuvants in addition to proteosomes augments the IgM and IgG antibody titres against OMP in these vaccines but GD3 antibody titres are unaffected. The application of proteosomes to enhance the immune response to GD3 extends the concept of the proteosome immunopotentiating system from lipopeptides to amphipathic carbohydrate epitopes such as cell-surface gangliosides. The demonstrated safety of meningococcal OMP in humans and the data in mice presented here suggest that proteosome vaccines have potential for augmenting the immunogenicity of amphipathic tumour antigens in humans.

Adjuvants, Immunologic↗
PubMed1986

Gangliosides in acute myeloid leukaemia (AML) and non-Hodgkin's lymphoma (NHL).

Gangliosides of human acute myelomonocytic leukaemia (AMMoL), acute monocytic leukaemia (AMoL) and lymphoblastoid (pre-B) lymphoma cells were analysed by overpressured thin-layer chromatography (OPTLC) followed by scanning densitometry. AMMoL cells were found to contain four gangliosides, viz. GM3 (47.2%), GM1 (31.8%), GD1a (7.5%) and an unidentified compound migrating between GM1 and GD1a (13.5%). In AMoL cells, six components were identified (GM3:51.3%, GM1:13.4%, GD3:7.8%, GD1a:4.7%, GD1b:6%, and an unidentified compound migrating between GM2 and GM1). The total gangliosides extracted from pre-B lymphoma cells of the hand-mirror variant were composed of 10 species (GM3:50.8%, GM2:11.2%, GM1:7.8%, GD3:2.3%, GD1a:1.1%, GD1b:2.2%, GT1:1.6%, and three unidentified components with chromatographic mobilities between GM2 and GD1a). Additional studies must still be performed to clarify the question as to whether ganglioside GD3 represent a qualitative glycolipid marker for AMoL and pre-B lymphoblastic lymphoma.

Chromatography, Thin Layer↗
PubMed1996

Vascular endothelial growth factor production is stimulated by gangliosides and TGF-beta isoforms in human glioma cells in vitro.

Vascular endothelial growth factor (VEGF) is an angiogenic factor which is known to be expressed in several malignancies including glioma. The effect of transforming growth factor-beta (TGF-beta) isoforms as well as gangliosides on VEGF production was investigated in human glioma cell lines. TGF-beta isoforms and gangliosides were found to differentially stimulate VEGF production by these cells. The ganglioside GD3 enhanced this release to the greatest extent and the stimulation was more marked in a glioblastoma cell line than in the two other anaplastic astrocytoma cell lines. These results suggest that both TGF-betas and gangliosides may act as indirect angiogenic factors by stimulating VEGF secretion.

Endothelial Growth Factors↗
PubMed1987

Ganglioside treatments reduce locomotor hyperactivity after bilateral lesions of the entorhinal cortex.

The present study evaluated the effects of exogenous gangliosides (membrane glycolipids) on open-field locomotor activity after bilateral lesions of the entorhinal cortex. Saline-treated rats showed a dramatic increase in activity followed by a time-dependent recovery (i.e. return toward control levels). Ganglioside-treated (50 mg/kg total gangliosides; i.m.) rats exhibited a similar pattern of changes in activity, except that their level of hyperactivity at 2-6 days postlesion was reduced. Thus, exogenous gangliosides lessened the severity of the lesion-induced hyperactivity, but did not enhance the total net recovery.

Animals↗
PubMed1990

Effects of dibutyryl cyclic adenosine monophosphate, ACTH(4-10) and gangliosides on nerve fiber regeneration after rat sciatic nerve tubulization.

Tubulization of sectioned rat sciatic nerves was used to evaluate the effect of dibutyryl cyclic adenosine monophosphate (db-cAMP), a fragment of the adrenocorticotrophic hormone (ACTH(4-10] and gangliosides on the regrowth of injured nerve processes. Four weeks post-operative, the number of myelinated fibers was counted at different levels of the lesioned sciatic nerves and the endoneurium surface of the bridging structure in the tube was measured. Animals treated with gangliosides and db-AMPc showed statistically significant differences compared to vehicle treated rats. The gangliosides have shown a beneficial effect but db-cAMP diminished the number of myelinated fibers. In this case, an implication of Schwann cell mitosis and migration is discussed. In spite of better results obtained in ACTH(4-10)-treated animals compared to controls, the differences did not attain a statistically significant level. These experiments confirm the beneficial effect of gangliosides on peripheral nerve regeneration and reveal a negative effect of db-cAMP in the regeneration chamber model.

Adrenocorticotropic Hormone↗
PubMed1994

Cell surface gangliosides are involved in the control of human glioma cell invasion in vitro.

The involvement of cell surface gangliosides in glioma cell invasion in vitro was examined using the ganglioside-specific antibody A2B5 and Matrigel-coated 8-microns porosity polycarbonate filters. Invasion of six cell lines derived from glial tumours of different histological grades was found to be markedly inhibited by A2B5 (50-96% inhibition) in a dose-dependent manner. Furthermore, exogenous gangliosides were found to prevent cell invasion when they were incubated with cells during the invasion assay. These results suggest that cell surface gangliosides are involved in glioma cell invasion in vitro, probably because of their adhesion-promoting action to basement membrane components.

Antibodies↗
PubMed1994

Gangliosides modulate the development of ethyl-nitrosourea induced brain tumors in rats.

The possible effect of gangliosides as biological modifiers of the ethyl-nitrosourea (ENU) model of neurocarcinogenesis in rats is studied. Wistar rats that were exposed to ENU during fetal life, were treated with gangliosides at a postnatal age corresponding to a stage of pretumor or microtumor development. The results obtained suggest that postnatal administration of gangliosides can influence the development of ENU-induced brain tumors, delaying the appearance of symptomatic neoplasms and improving survival with respect to controls. This finding suggests the potential usefulness of gangliosides in the control of neuroectodermal tumors.

Animals↗
PubMed1983

Decreased ganglioside neuraminidase activity in fibroblasts from mucopolysaccharidosis patients. Inhibition of the activity in vitro by sulfated glycosaminoglycans and other compounds.

The neuraminidase activities towards the ganglioside substrates GD1a, GD3 and GM3 were found to be markedly diminished in homogenates of fibroblasts cultured from patients with various genetic mucopolysaccharidoses. Mixing normal and patients' fibroblast homogenates revealed this effect to be due to the presence of diffusible inhibitors. The neuraminidase acting on the trisaccharide sialyllactose, on the other hand, showed normal activity in all the cell lines tested. Experiments in vitro revealed the sulfated glycosaminoglycans chondroitin 4-sulfate and heparin, the polysaccharide dextran sulfate, and the trypanocidal drug suramin to be strongly inhibitory on the ganglioside GD1a neuraminidase activity of normal fibroblast homogenates. Regarding chondroitin 4-sulfate, this inhibition was of the non-competitive type. A disulfated tetrasaccharide prepared from chondroitin 4-sulfate, on the other hand, was not at all inhibitory. These and additional findings led us to propose a model for the interaction between enzyme and inhibitor, involving a 'clamping' mechanism by the polysulfated compounds. We conclude that the decreased ganglioside neuraminidase activities of mucopolysaccharidosis fibroblasts are due to an inhibition by the accumulated sulfated glycosaminoglycans and that such inhibition is responsible for the storage of certain gangliosides in the tissues of the patients.

Gangliosides↗
PubMed1984

Structure related phylogenetic variations in brain gangliosides of vertebrates.

The concentration and composition of brain gangliosides from five brain structures of vertebrate species belonging to the classes of Chondrichthyes, Osteichthyes, Reptilia, Aves and Mammalia were investigated. The complexity of brain ganglioside composition is strikingly reduced over phyletic lines. In lower vertebrates there is only little variation in the ganglioside pattern between the different brain structures, whereas in higher vertebrates differences distinctly occurred. A similarity over phyletic lines of ganglioside pattern was only noted in phylogenetically old brain structures as for instance in the medulla oblongata and the brain stem.

Animals↗
PubMed1994

Phylogenetic conservation of ganglioside GD3 expression during early vertebrate ontogeny.

Gangliosides were investigated in adult brains and in 5-vesicle stage embryos of representatives belonging to the four vertebrate classes: Chondrichthyes, Amphibia, Aves and Mammalia. Considerable variability in brain ganglioside composition and concentration was observed among the adult vertebrates. The ganglioside patterns of the developmentally matched vertebrate embryos were similar in that each comprised GD3 as the predominant ganglioside. The phylogenetic conservation of abundant GD3 expression during early vertebrate ontogeny is interpreted as biochemical evidence consistent with von Baer's theory of increasing differentiation and suggests that GD3 is of critical importance for normal vertebrate development.

Animals↗
PubMed1983

Muscle reinnervation--III. Motoneuron sprouting capacity, enhancement by exogenous gangliosides.

Rat soleus muscle was partially denervated by resecting the L5 mixed nerve. Muscle reinnervation was monitored 10, 30 and 50 days after surgery. The extent of recovery was found to be dependent on the number of axons remaining in the muscle and appeared not to be influenced by the time allowed. If animals were treated daily with 5 mg/kg of gangliosides the enlargement of the motor units was further enforced. The index of sprouting (expressed as the ratio between the percentage of muscle reinnervation due to a certain number of motor neurons in reinnervation and in normal conditions) was increased in a significant way by gangliosides treatment, i.e. one motor unit can expand up to about 4.5-fold, but if the animal was treated with gangliosides the motor unit can expand up to about 6.3-fold. These results showed that motoneuron sprouting capacity is increased by treatment animals with gangliosides.

Animals↗
PubMed1995

Pyramidal neurons with ectopic dendrites in storage diseases exhibit increased GM2 ganglioside immunoreactivity.

Cortical pyramidal neurons in several types of neuronal storage diseases have been shown by Golgi staining to sprout axon hillock-associated dendritic processes. Based on the relative incidence of this ectopic dendritogenesis, and on quantitative analyses of gangliosides in these same tissues, it has been proposed that abnormal accumulation of a specific metabolic product, GM2 ganglioside, is the pivotal event leading to re-initiation of dendritic sprouting [Siegel D. A. Walkley S.U. (1994) J. Neurochem. 62, 1852-1862]. In the present study, a monoclonal antibody was used to determine the cellular location of this ganglioside within the cerebral cortex of animal models of storage diseases with and without ectopic dendrite growth. Diseases exhibiting ectopic dendritogenesis included inherited and swainsonine-induced (juvenile-onset) alpha-mannosidosis, mucopolysaccharidosis type I, Niemann-Pick disease type C, and GM1 and GM2 gangliosidosis. Conditions lacking ectopic dendrite growth included adult-onset swainsonine-induced alpha-mannosidosis, fucosidosis, neuronal ceroid lipofuscinosis (Batten disease) and normal, mature brain. Immunocytochemical staining for GM2 ganglioside indicated that diseases exhibiting new dendritic sprouting with the exception of GM1 gangliosidosis, exhibited abundant GM2-like immunoreactivity within the cortical pyramidal cell population, whereas diseases without dendritic sprouting had GM2-like immunoreactivity limited to glia and/or to non-pyramidal neurons. Cortical tissues from normal animals at comparable ages and processed by similar procedures exhibited occasional glial cell staining but little or no neuronal labelling. Mechanisms by which normal cortical pyramidal regulate dendritic initiation are poorly understood. However, it is known that this event is developmentally restricted, occurring only during early brain development.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of spontaneous bioelectric activity and gangliosides on cell survival in vitro.

Chronic suppression of spontaneous bioelectric activity in spinal cord explants in the presence of tetrodotoxin (TTX) during network formation caused a large reduction in cell number (lowered DNA levels). The addition of gangliosides failed to protect against this cell loss. Conversely, the omission of galactose from the growth medium had no effect on DNA levels. It was concluded that the presence or absence of afferent selectivity is unlikely to require the survival of a regionally specific subpopulation of preferred dorsal root ganglion target cells. Neocortical explants also showed a large reduction in DNA levels following chronic TTX treatment, and morphometric analysis confirmed that neuronal survival was affected to the same degree. Chronic ganglioside supplementation failed to influence DNA and cell counts in either control or TTX-treated explants, but one of the added gangliosides (GD1a) stimulated extensive neuritic outgrowth in electrically silenced cultures. Particular ganglioside species, therefore, may exert a growth stimulating influence that can partially compensate for the absence of bioelectric self-stimulation during early development.

Animals↗
PubMed1989

[Abnormal gangliosides in the plasma of alcoholics].

Gangliosides were isolated from plasma of alcoholics. The pattern of gangliosides was compared with that of healthy humans. Up to seven fractions of gangliosides could be detected. In healthy subjects the following pattern was found: GM3 38.2%, SPG 6.0%, GD3 30.2%, GD1a 10.6%, GD1b 4.8%, GT1b 7.9%, GQ1b 2.2%. In alcoholics, significant differences were observed in the main ganglioside fractions GM3 (52.6%) and GD3 (17.5%).

Adult↗
PubMed1994

Exogenous GM1 ganglioside effects on conductive and sensorineural hearing losses.

Both CBA/J mice with neonatal cochlea removals and CBA/J mice with neonatal atresias of the external auditory meatus have significantly smaller ventral cochlear nucleus is greater in the mice with cochlea removals, but the soma area reduction is greater in the mice with external auditory meatus atresias. GM1 gangliosides were subcutaneously injected daily into a group of CBA/J mice with conductive hearing loss caused by neonatal removals of their left external auditory meatus, and into a group of CBA/J mice unilaterally deafened by left cochlea removals. In the mice with conductive hearing loss, the ganglioside treatment significantly ameliorated the atrophy of spiral ganglion neurons, ventral cochlear nucleus neurons, and ventral cochlear nucleus volume. In unilaterally deafened mice, the ganglioside treatment had no measurable effect on the atrophy of ventral cochlear nucleus neurons or of ventral cochlear volume. It is suggested that GM1 ganglioside treatment potentiates growth factors which sustain spiral ganglion integrity and that this sustained activity of the spiral ganglion in turn maintains the integrity of the cochlear nuclei.

Animals↗
PubMed1995

Auditory brainstem responses of CBA/J mice with neonatal conductive hearing losses and treatment with GM1 ganglioside.

Exogenous administration of GM1 ganglioside to CBA/J mice with a neonatal conductive hearing loss ameliorates the atrophy of spiral ganglion neurons, ventral cochlear nucleus neurons, and ventral cochlear nucleus volume. The present investigation demonstrates the extent of a conductive loss caused by atresia and tests the hypothesis that GM1 ganglioside treatment will ameliorate the conductive hearing loss. Auditory brainstem responses were recorded from four groups of seven mice each: two groups received daily subcutaneous injections of saline (one group had normal hearing; the other had a conductive hearing loss); the other two groups received daily subcutaneous injections of GM1 ganglioside (one group had normal hearing; the other had a conductive hearing loss). In mice with a conductive loss, decreases in hearing sensitivity were greatest at high frequencies. The decreases were determined by comparing mean ABR thresholds of the conductive loss mice with those of normal hearing mice. The conductive hearing loss induced in the mice in this study was similar to that seen in humans with congenital aural atresias. GM1 ganglioside treatment had no significant effect on ABR wave I thresholds or latencies in either group.

Acoustic Stimulation↗