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At least 1,621 records · Page 90Linked to original sources
PubMed1989

Continued administration of GM1 ganglioside is required to maintain recovery from neuroleptic-induced sensorimotor deficits in MPTP-treated mice.

Injection of a dose of haloperidol that has no obvious behavioral effects in normal mice, produces akinesia, catalepsy, and sensory neglect in MPTP-treated mice. Chronic GM1 ganglioside administration improves the behavioral impairments, partially restores striatal dopamine (DA) content and prevents DA D-2 receptor up-regulation. Discontinuation of GM1 ganglioside treatment results in a time-dependent decline of striatal DA content to pretreatment pathological levels, return of haloperidol-induced sensorimotor deficits and a rise of DA D-2 receptor density in the striatum. Apparently, continuous administration of GM1 ganglioside is necessary to maintain the biochemical and behavioral recovery in the MPTP-treated mouse. These observations may provide useful cues for understanding the mechanism of action of GM1 ganglioside.

Animals↗
PubMed1992

Ganglioside therapy of type I diabetes: enhancement of hyperglycemia in the low dose streptozotocin model.

The therapeutic potential of bovine brain gangliosides on the development of insulin deficient diabetes was analysed. Daily ganglioside administration (50 mg/kg body weight) caused a more pronounced rise of blood glucose levels (p less than 0.05) in low dose streptozotocin treated mice, a model of human type I diabetes. Hyperglycemia induced by the injection of a single high dose of streptozotocin was slightly increased by ganglioside administration (not significant). The previously reported protective effect of bovine brain gangliosides on the development of diabetes in NOD mice was thus not found in a second mouse model.

Animals↗
PubMed1993

Effect of gangliosides on Trypanosoma cruzi infection in mice.

Albino Swiss male mice were inoculated with Trypanosoma cruzi, Tulahuen strain trypomastigotes, and separated into three groups: control, without treatment; control, treated with Nifurtimox 25 mg/day; and experimental, treated with total brain gangliosides 1 mg/day, intramuscular. The treatment was started immediately after infection and maintained for 4 weeks. Parasitemia was determined twice a week and histopathological analyses of hearts were performed. The parasitemia was significantly lowered by the ganglioside treatment. All untreated mice died by day 14 post infection. Survival at day 30 was 96% for mice in the experimental group. Hearts from untreated animals showed acute chagasic myocarditis, while those from mice treated with gangliosides presented only minor mononuclear infiltration. The effect of gangliosides is probably due to interference of parasite penetration into the host cells.

Animals↗
PubMedDate not supplied

The effect of exogenous GM1 ganglioside on kindled-amygdaloid seizures.

The effects of 12 daily doses of 30 mg/kg GM1 ganglioside i.p. on the acquisition of kindled-amygdaloid seizures in the rat was studied. No modification in the rate of kindling or the expression of the elicited seizures was noted during the acquisition phase. Further studies with additional fully amygdaloid kindled rats failed to show significant modification of suprathreshold or threshold elicited seizures after single 30-60 mg/kg i.p. doses of GM1 ganglioside. Despite previous studies which have shown antibodies to GM1 ganglioside to be convulsive, no anticonvulsant activity was demonstrated in this study with exogenous GM1 ganglioside using a battery of kindled-amygdaloid seizure tests in the rat.

Amygdala↗
PubMed1988

Lesioning and recovery of the serotoninergic hippocampal afferents: differential effects of GM1 ganglioside.

The effects of administration of GM1 ganglioside on the content of 5-HT and of 5-HIAA in the hippocampus after two different types of lesions of the serotoninergic afferents to the hippocampus were studied. The first type of lesion consisted in severing the dorsal hippocampal afferents. This caused a monolateral decrease of the content of 5-HT and of 5-HIAA in the hippocampal by 60 and 38%, respectively. Since a partial spontaneous recovery occurred after 40-60 days, this model has been used in the past to study sprouting phenomena in the 5-HT system. Daily intraperitoneal administration of GM1 ganglioside (30 mg/kg), for up to 60 days, did not modify this partial recovery. The second lesion consisted of electrolytic damage to a mesencephalic area, where scattered 5-HT cells projecting to the hippocampus are known to be located. The content of 5-HT and 5-HIAA in the hippocampus, ipsilateral to this lesion, decreased by 37 and by 26%, respectively. Administration of GM1 ganglioside (30 mg/kg/day for 6-14 days) partially antagonized the decrease of both 5-HT and 5-HIAA induced by the lesion. These data are in agreement with the view that gangliosides may reduce neuronal injury after mechanical lesions, with a mechanism which is probably not related to neuronal sprouting.

Afferent Pathways↗
PubMed1989

Gangliosides mediate inhibitory effects of tetanus and botulinum A neurotoxins on exocytosis in chromaffin cells.

Bovine chromaffin cells in monolayer culture were preloaded with 3H-NA (noradrenaline) and subsequently stimulated with carbachol. Botulinum A neurotoxin partially inhibited the evoked release of 3H-NA and the basal efflux of the hormone. The inhibition of evoked release did not exceed 40%, although the cells were exposed to 10 micrograms/ml of toxin for 6 days. The inhibitory effect of botulinum A neurotoxin was neutralized by its antibodies. In contrast to botulinum A neurotoxin, tetanus toxin at even higher concentrations did not influence evoked release. This difference in sensitivity could be explained by the ganglioside pattern of chromaffin cells. Ganglioside GD1a, a putative receptor for botulinum A neurotoxin, could be identified in lipophilic extracts, whereas the tetanus toxin binding gangliosides GT1b and GD1b could not be detected by means of thin-layer chromatography. Treatment of the cells with neuraminidase abolished both, GD1a and the inhibitory effect of botulinum A neurotoxin. Incubation of chromaffin cells with a mixture of gangliosides (21% GM1, 44% GD1a, 15% GD1b, 20% GT1b) not only increased the efficacy of botulinum A neurotoxin but also made the cells sensitive towards tetanus toxin. The concentration-response curve of botulinum A neurotoxin was shifted to the left about five-fold and the maximum inhibition of evoked release was increased up to 60%, even though the cells were exposed to the toxin for 3 days only. In contrast, the maximum inhibition that could be achieved by tetanus toxin was 40%. The results indicate that polysialogangliosides are important for the intracellular accumulation of these clostridial neurotoxins.

Adrenal Medulla↗
PubMed1989

Differences in susceptibility of rat liver and brain sialidases to ethanol and gangliosides.

Based on reports that ethanol can decrease the level of sialic acid (SA) (neuraminic acid) in several tissues, we tested the hypothesis that ethanol promotes SA cleavage by enhancing the activity of sialidases (neuraminidases). We also investigated whether brain and liver sialidases have the same response to ethanol and gangliosides, especially since our prior studies have demonstrated that gangliosides could antagonize ethanol-induced behavior. Experiments were conducted on homogenates of brain and liver and of liver slices of adult rats. In liver slices, cleavage of SA did not fall in proportion to the ethanol-induced inhibition of sialidase; in fact, at 0.1 M ethanol, free SA increased, even though sialidase was inhibited. Brain sialidase activity on endogenous sialoglycoconjugates was much more resistant to ethanol than liver sialidase and was fully active even in concentrations as high as 1 M. When gangliosides were incubated with liver slices in the absence of ethanol, sialidase was markedly stimulated. The ethanol-induced inhibition of sialdase in liver slices was mimicked by sorbitol, suggesting that the inhibition may be caused by a shift in redox state as a result of increased NADH. The ethanol metabolite, acetaldehyde, does not seem to be a factor, because sialidase inhibition still occurred when slices were incubated with ethanol containing pyrazole. The results indicate that ethanol promotes the accumulation of free SA in liver without stimulating sialdase; our other work suggests that the cause is an increase in accessibility to sialoglycoconjugates rather than decreased utilization of SA. Brain and liver sialidases clearly respond differently to both ethanol and gangliosides.

Animals↗
PubMed1985

Ganglioside modulation of lipopolysaccharide-initiated complement activation.

Highly purified preparations of mouse gangliosides have been demonstrated to bind to purified preparations of lipopolysaccharide (LPS). In some instances, the binding has been demonstrated to be dependent upon the presence of sialic acid in the ganglioside preparation. The binding of gangliosides to LPS from the deep rough Salmonella minnesota Re mutant has suggested that the interaction involves the lipid A-2-keto-3-deoxyoctulosanate region of the LPS macromolecule. The interaction between gangliosides and LPS has been demonstrated to result in an abrogation of lipid A dependent activation of the classical pathway of serum complement by Re LPS. Surprisingly, however, the presence of sialic acid containing glycolipids has been shown to enhance significantly the capacity of LPS to initiate activation of the alternative pathway of complement. These data suggest that sialic acid can enhance as well as inhibit the formation of a stable alternative-pathway C3 convertase.

Animals↗
PubMed1985

Brain gangliosides in birds with different types of postnatal development (nidifugous and nidicolous type).

Developmental profiles of 14 different brain gangliosides were followed from the first day after hatching to the adult stage in two bird species representing different strategies of posthatch development: the nidifugous type (leaving the nest directly post-hatch, e.g. quail) and the nidicolous type (remaining for longer period in the nest, e.g. finch). In the zebra finch, parallel with a striking increase in ganglioside concentration, two main postnatal changes in the ganglioside composition occurred: after hatching, concomittantly to an increased outgrowth of nerve fibers and synaptogenesis, the polysialogangliosides GQ1b and GP decreased in favour of the less polar fractions GD1b, GD1a and GT1b. The second period of changes started with the onset of myelination and was characterized by an increase of GM1 and GM1'. The results obtained for quails were in close agreement with those of chicken, showing only slight postnatal changes due to the nearly completed morphological differentiation. These data show that gangliosides are useful biochemical markers for brain development, indicating successive periods of brain maturation by means of preferential biosynthesis of specific fractions regardless of the type of development.

Age Factors↗
PubMed1990

Differential recognition of a set of O-acetylated gangliosides by monoclonal antibodies RB13-2, D1.1, and JONES during rat brain development.

Monoclonal antibodies (Mab) RB13-2, JONES, and D1.1 all recognize gangliosides expressed on the surface of prenatal rat brain cells. As shown by high-performance thin-layer chromatography (HPTLC) immunoblotting of enriched rat brain gangliosides from different stages of development, all these Mabs bind to O-acetylated GD3 and (weakly) to an as yet unidentified double-band. Both Mab RB13-2 and Mab D1.1 recognize two additional minor gangliosides. Immunofluorescence analyses of frozen serial sections of prenatal rat brain show that, in addition to the cell subpopulations stained with all three antibodies, Mab RB13-2 and Mab D1.1 recognize further subpopulations of neural cells. These additional Mab JONES-negative cells apparently express minor ganglioside(s) identified in the immunoblots.

Acetylation↗
PubMed1992

Gangliosides prevent the inhibition by K-252a of NGF responses in PC12 cells.

K-252a, a general kinase inhibitor, selectively blocks the actions of nerve growth factor (NGF) in PC12 cells. Since gangliosides have been reported to modulate neuronal cell responsiveness to NGF and to regulate several protein kinases, the ability of these compounds to reverse the inhibition by K-252a was tested. Parameters at both short- and long-term times following treatment of PC12 cells with NGF were analyzed which are known to be either transcription-dependent or -independent events. Gangliosides were found to completely prevent the inhibition by K-252a of NGF-induced neurite regeneration and c-fos induction, and partially also that of protein kinase N activation. The ganglioside protective effects were concentration-dependent and required the intact molecule. These findings raise the possibility that gangliosides might affect a specific pathway of NGF responses sensitive to inhibition by K-252a.

Animals↗
PubMed1989

Schwann cells influence the expression of ganglioside GD3 by rat dorsal root ganglion neurons.

Cultured rat dorsal root ganglion neurons expressed ganglioside GD3 when grown in the absence of non-neuronal cells. Among the non-neuronal cells, fibroblasts, but not Schwann cells, also stained for ganglioside GD3 during the first few days in culture. When neurons were combined with non-neuronal cells the intensity of the GD3 immunoreactive neuronal processes was diminished at sites contacted by Schwann cells. This contact-mediated effect was specific for ganglioside GD3 since no difference was seen with A2B5 or JONES antibodies, which recognize different gangliosides.

Animals↗
PubMed1993

Gangliosides and bacterial toxins in Guillain-Barré syndrome.

Autoimmune factors are strongly favoured as mediating Guillain-Barré syndrome (GBS); however, the precise mechanisms by which this occurs remain unknown. Microbial infections in a susceptible host resulting in an idiosyncratic immune response which cross-reacts with nerve constituents still remains the most plausible working hypothesis on which much current research is based. Considerable recent evidence indicates that this humoral immune response is at least in part directed to gangliosides. Interestingly, many bacterial toxins, including botulinum and tetanus neurotoxins, also bind to gangliosides and induce diseases with some similarities to GBS. This article discusses the evidence in favour of a pathogenic role for anti-ganglioside antibodies in GBS in the context of our knowledge of the biology of gangliosides and the factors that determine their immunogenicity.

Antibodies, Bacterial↗
PubMed1994

T cell-dependent activity of ganglioside GM1-specific B cells in Guillain-Barré syndrome and multifocal motor neuropathy in vitro.

Synthesis of anti-ganglioside GM1 antibodies of the IgM class by peripheral blood mononuclear cells (PBMNC) from patients with immune-mediated neuropathies and motor neuron diseases and from normal controls was stimulated by Pokeweed mitogen (PWM) in vitro. In patients with acute Guillain-Barré syndrome or multifocal motor neuropathy and high serum titers of IgM anti-ganglioside GM1 antibodies this culture response was greatly enhanced as compared to controls and already detectable in unstimulated cultures. Limiting dilution analysis demonstrated high frequencies of GM1-specific B cells in these patients. Anti-ganglioside GM1 antibodies of the IgG and IgA class were only produced by PBMNC from patients with Guillain-Barré syndrome corresponding to serum titers. In cultures taken at intervals over 6 months in vitro B cell activity for IgM, IgG and IgA anti-ganglioside GM1 antibodies in two Guillain-Barré syndrome patients declined accompanied by clinical improvement and falling serum titers. We conclude that GM1-specific PWM-responsive B cells pre-exist in peripheral blood and respond to T cell-dependent stimulation in Guillain-Barré syndrome and multifocal motor neuropathy.

Adult↗
PubMed1994

Effect of pure bovine brain-derived gangliosides on normal human B cell proliferation in vitro.

Pure gangliosides obtained from bovine brain including GM1, GD1b, GT1b and asialo-GM1 (GA1) did not induce normal human B cell proliferation in vitro. No B cell proliferation was observed either when GM1 was tested in the presence of interleukin-2 (IL-2), IL-4 or IL-6. Furthermore, the proliferative responses of human B cells induced by Staphylococcus aureus Cowan I (SAC), a T cell-independent B cell mitogen, were inhibited by these gangliosides. The degree of inhibition was influenced by ganglioside-bound sialic acid, although sialic acid per se was not inhibitory. Strongest inhibition was observed in the presence of GT1b (EC50 8.8 microM/10(5) B cells) and lowest in the presence of GA1 (EC50 129.5 microM/10(5) B cells) with intermediate values for GM1 and GD1b. GM1 inhibition of SAC-induced B cell proliferation did not represent cytotoxic effects and was still evident when GM1 was added 24-48 h after the beginning of the cultures. GM1 inhibition of SAC-induced proliferation was not reversed by the addition of IL-2, IL-4, IL-6 or their combination. In addition, GM1 inhibited the ILs-driven proliferative responses of SAC-induced B cell blasts. However, no inhibition of Epstein-Barr virus-induced B cell proliferative responses was observed. In conclusion, these results show that bovine brain-derived gangliosides do not induce proliferative responses of normal human B cells but, on the contrary, inhibit B cell responses induced by SAC.

Animals↗
PubMed1993

Anti-ganglioside GD1a monoclonal antibody recognizes senile plaques in the brains of patients with Alzheimer-type dementia.

Immunohistochemical staining of brain tissues from patients with Alzheimer-type dementia (ATD) with an anti-GD1a ganglioside monoclonal antibody is described. This monoclonal antibody labeled some myelinated nerve fibers in brain tissue from a non-demented control subject, in which the staining was distributed preferentially in the cerebral white matter. In brain tissue from ATD patients, some senile plaques (SPs) were also immunostained, with the strongest staining in the hippocampal subiculum, where most of the SPs appeared as clusters of dots. When the immunohistochemical staining was compared with a methenamine silver stain (MS stain), these immunopositive dots were found to be argyrophilic dystrophic (or degenerating) neurites. No amyloid deposits, neurofibrillary tangles (NFTs) or neuropil threads were immunostained. In this study, we used sections cut from formaldehyde-fixed brain samples with a cryostat and pretreatment of the sections with chloroform was essential to obtain positive immunostaining. Gangliosides have been demonstrated to possess some neurotrophic activity and to be localized on cell surface membranes. The localization of the GD1a ganglioside observed in dystrophic neurites suggests that such neurites accumulate a membranous component. In addition, the accumulation of the GD1a ganglioside in SPs suggests it may contribute to SP formation.

Aged↗
PubMed1995

Neuronal expression of a minor monosialosyl ganglioside GM1b in rat brain: immunochemical characterization using a specific monoclonal antibody.

Monoclonal antibodies (mAbs) against GM1b ganglioside were raised by immunizing NZB/n mice with the antigen purified from bovine brains, and the details of binding specificity of the mAbs were characterized. Anti-GM1b mAb, termed NA-6, reacted specifically with GM1b (NeuAc) and GM1b(NeuGc). NA-6 antibody did not react with other structurally related gangliosides, indicating that the antibody recognizes NeuAc or NeuGc alpha 2-3Gal beta 1-4GalNAc beta 1-4Gal structure. Using NA-6 antibody, GM1b ganglioside in developing rat brain was investigated by TLC/enzyme-immunostaining and detected first on gestational day 16. The specific content of brain GM1b increased until postnatal day 10, and then gradually decreased in later stage of development. Immunohistochemically GM1b was found in proximal dendrites and cell bodies of neurons in extensive regions of adult rat brain. The immunoreactivity tended to be confined in patch-like clusters on cell membranes, as typically found in the hippocampus and neocortex. The GM1b synthase activity, when assayed in the cerebellar microsome proteins, was significantly reduced in lurcher mutant mouse that is devoid of both cerebellar granule and Purkinje cells. These findings demonstrate that GM1b ganglioside exists in neurons and is actively synthesized during the development in rat brain.

Animals↗
PubMed1989

Effect of gangliosides on diabetic peripheral neuropathy.

The effect of subcutaneously injected gangliosides on diabetic peripheral neuropathy was assessed in 26 diabetic patients with neuropathy, 20 of whom received 100 mg daily 5 days per week for 12 weeks in a randomised single-blind cross-over placebo-controlled study and six of whom, with painful neuropathy, received the same quantity of gangliosides for the same length of time but no placebo. Subjective symptoms of lower limb neuropathy improved on gangliosides but not on placebo (P = 0.01). The amplitude of the peroneal nerve muscle action potential increased on gangliosides and declined on placebo (P = 0.05), but no other significant changes were observed in nerve conduction or in any other measurable sign of lower limb somatic nerve function or of cardiovascular autonomic function.

Adult↗