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Autism spectrum disorder (ASD) is a neurodevelopmental disorder that cannot be cured. The ASD rat model was developed in this study to demonstrate the role and mechanism of ganglioside GM1 (GM1). Rats were given valproic acid (VPA) to create the ASD rat model. The rats' behaviors were assessed using the Y-maze test, open-field test, three-chamber social interaction test, and Morris water maze test. Relative levels of glutathione (GSH), malondialdehyde (MDA), catalase (CAT), reactive oxygen species (ROS), and superoxide dismutase (SOD) were quantitated using relative kits. Nissl, TUNEL, immunofluorescent, and immunohistochemistry staining techniques were used. GM1 treatment improved the ASD model rats' behavior disorders, including locomotor activity and exploratory behavior, social interaction, learning and memory capacity, and repetitive behavior. Following GM1 injection, striatal neurons grew and apoptosis decreased. GM1 reduced the excessively elevated α-Syn in ASD by encouraging autophagy. The behavior disorder of ASD model rats was exacerbated by autophagy inhibition, which also increased α-Syn levels. By increasing autophagy, GM1 reduced α-Syn levels and, ultimately, improved behavioral abnormalities in ASD model rats. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is slowly progressing neurodegenerative disorder that affects millions of patients worldwide. While effective symptomatic therapies for PD exist, there is no currently available disease modifying agent to slow or stop the progression of the disease. Many years of research from various laboratories around the world have provided evidence in favor of the potential ability of GM1 ganglioside to be a disease modifying agent for PD. In this paper, information supporting the use of GM1 as a disease modifying therapeutic for PD is reviewed along with information concerning the role that deficiencies in GM1 ganglioside (and potentially other important brain gangliosides) may play in the pathogenesis of PD. [ABSTRACT FROM AUTHOR]

Ketamine is a widely used analgesic and anesthetic in obstetrics and pediatrics. Ketamine is known to promote neuronal death and cognitive dysfunction in the brains of humans and animals during development. Monosialotetrahexosyl ganglioside (GM1), a promoter of brain development, exerts neuroprotective effects in many neurological disease models. Here, we investigated the neuroprotective effect of GM1 and its potential underlying mechanism against ketamine-induced apoptosis of rats. Seven-day-old Sprague Dawley (SD) rats were randomly divided into the following four groups: (1) group C (control group: normal saline was injected intraperitoneally); (2) group K (ketamine); (3) group GM1 (GM1 was given before normal saline injection); and (4) GM1+K group (received GM1 30 min before continuous exposure to ketamine). Each group contained 15 rats, received six doses of ketamine (20 mg/kg), and was injected with saline every 90 min. The Morris water maze (MWM) test, the number of cortical and hippocampal cells, apoptosis, and AKT/GSK3β pathway were analyzed. To determine whether GM1 exerted its effect via the PI3K/AKT/GSK3β pathway, PC12 cells were incubated with LY294002, a PI3K inhibitor. We found that GM1 protected against ketamine-induced apoptosis in the hippocampus and cortex by reducing the expression of Bcl-2 and Caspase-3, and by increasing the expression of Bax. GM1 treatment increased the expression of p-AKT and p-GSK3β. However, the anti-apoptotic effect of GM1 was eliminated after inhibiting the phosphorylation of AKT. We showed that GM1 lessens ketamine-induced apoptosis in the hippocampus and cortex of young rats by regulating the PI3K/AKT/GSK3β pathway. Taken together, GM1 may be a potential preventive treatment for the neurotoxicity caused by continuous exposure to ketamine. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the effect of Monosialoganglioside (GM1) on inflammation after spinal cord injury (SCI), and to explore the underlying mechanism. Thirty-six healthy adult Sprague Dawley (SD) rats were randomly allocated into three groups: sham group (n = 12), SCI group (n = 12), or SCI+GM1 group (n = 12). Protein expressions of inflammatory mediators including interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) and cyclooxygenase‑2 (COX-2) were determined by enzyme-linked immunosorbent assay (ELISA) assay. The expression of phospho-NF-κB p65 (p-p65), phospho-IκBα (p-IκBα), toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) were analyzed by western blot analysis. Hindlimbs motor function was assessed by Basso, Beattie, and Bresnahan (BBB) rating scale. It is shown that SCI induced the up-regulation of TLR4, NF-κB, and inflammatory cytokines in the injured rat spinal cord. Treatment of GM1 after SCI significantly suppressed SCI-induced inflammatory activity, iNOS and COX-2 protein expression, and attenuated the activation of NF-κB and TLR4 signaling. Administration of GM1 also significantly ameliorated SCI-induced hindlimb locomotion deficits. In conclusions, Post-SCI treatment of GM1 alleviates inflammation and improves motor function via inhibiting the TLR4/NF-κB pathway. [ABSTRACT FROM AUTHOR]

Developmental lead (Pb) exposure involves various serious consequences, especially leading to neurotoxicity. In this study, we examined the possible role of monosialoganglioside (GM1) in lead-induced nervous impairment in the developing rat. Newborn male Sprague-Dawley rat pups were exposed to lead from birth for 30 days and then subjected to GM1 administration (0.4, 2, or 10 mg/kg; i.p.) or 0.9% saline. The results showed that developmental lead exposure significantly impaired spatial learning and memory in the Morris water maze test, reduced GM1 content, induced oxidative stress, and weakened the antioxidative systems in the hippocampus. However, co-treatment with GM1 reversed these effects. Moreover, GM1 counteracted lead-induced apoptosis by decreasing the expression of Bax, cleaved caspase-3, and by increasing the level of Bcl-2 in a dose-dependent manner. Furthermore, we found that GM1 upregulated the expression of SIRT1, CREB phosphorylation, and BDNF, which underlie learning and memory in the lead-treated developing rat hippocampus. In conclusion, our study demonstrated that GM1 exerts a protective effect on lead-induced cognitive deficits via antioxidant activity, preventing apoptosis, and activating SIRT1/CREB/BDNF in the developing rat hippocampus, implying a novel potential assistant therapy for lead poisoning. [ABSTRACT FROM AUTHOR]

Understanding the role of neural membrane in translocation and action of neurohormone is of great importance. Luteinizing hormone-releasing hormone (LHRH) is a neuropeptide hormone and it acts as a final signaling molecule by stimulating the synthesis of LH and FSH to maintain reproduction in all vertebrates. The receptors of LHRH are found in breast tumors and pituitary gland in the brain. Moreover, neural plasma membrane is also found to contain specific binding site for LHRH. The mechanism by which LHRH binds to membrane before it binds to the receptors is a very critical step and can have a profound impact upon the translation of peptide across the membrane. A complex form of glycosphingolipids known as Ganglioside is an important component of plasma membrane of nerve cells and breast tumor tissues. They play an important role in various physiological membrane processes. Therefore, the interaction of ganglioside-containing membrane with LHRH might be crucial in aiding the LHRH to translate through the neural membrane and reach its receptor for binding and activation. Using CD, UV-Absorbance, and fluorescence spectroscopy, the effect of Ganglioside Monosialo 1(GM1)-induced conformational changes of LHRH in the presence of Cholesterol (CHOL)/Sphingomyelin (SM) and GM1/CHOL/SM vesicles was studied. The aforesaid spectroscopic studies show that LHRH is able to bind with both the vesicles, but GM1-containing vesicles interact more effectively than vesicles without GM1. CHOL/SM vesicles partially disturb the conformation of the peptide. Moreover, binding of LHRH to GM1/CHOL/SM vesicles induces loss of conformational rigidity and attainment of a random coil. [ABSTRACT FROM AUTHOR]

Fluorescence correlation spectroscopy (FCS) is a sensitive analytical tool for investigation of processes accompanied by changes in the mobility of molecules and complexes. In the present work, peak intensity analysis (PIA) in combination with the solution stirring using FCS setup was applied to explore the interaction between fluorescently labeled protein ligands and corresponding receptors located on membranes. In the system composed of biotinylated liposomes and fluorescently labeled streptavidin as a ligand, PIA allowed us to determine the optimum receptor concentration and demonstrate the essential dependence of the binding efficacy on the length of the linker between the biotin group and the polar head group of the lipid. The binding was dependent on the size of liposomes which was varied by lipid extrusion through filters of different pore diameters. The sensitivity of the method was higher with the liposomes of larger sizes. The PIA approach can be applied not only to liposomes but also to relatively large objects, e.g., erythrocytes or Sepharose beads derivatized with lactose as a receptor for the binding of viscumin and ricin. [ABSTRACT FROM AUTHOR]

Gangliosides (sialic acid-containing glycosphingolipids) are abundant in neurons of all animal species and play important roles in many cell physiological processes, including differentiation, memory control, cell signaling, neuronal protection, neuronal recovery, and apoptosis. Gangliosides also function as anchors or entry points for various toxins, bacteria, viruses, and autoantibodies. GM1, a ganglioside component of mammalian brains, is present mainly in neurons. GM1 is one of the best studied gangliosides, and our understanding of its properties is extensive. Simple and rapid procedures are available for preparation of GM1 as a natural compound on a large scale, or as a derivative containing an isotopic radionuclide or a specific probe. Great research interest in the properties of GM1 arose from the discovery in the early 1970s of its role as receptor for the bacterial toxin responsible for cholera pathogenesis. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder whose pathogenesis involves production and aggregation of amyloid-β peptide (Aβ). Aβ-induced toxicity is believed to involve alterations on as Na,K-ATPase and acetylcholinesterase (AChE) activities, prior to neuronal death. Drugs able to prevent or to reverse these biochemical changes promote neuroprotection. GM1 is a ganglioside proposed to have neuroprotective roles in AD models, through mechanisms not yet fully understood. Therefore, this study aimed to investigate the effect of Aβ1-42 infusion and GM1 treatment on recognition memory and on Na,K-ATPase and AChE activities, as well as, on antioxidant defense in the brain cortex and the hippocampus. For these purposes, Wistar rats received i.c.v. infusion of fibrilar Aβ1-42 (2 nmol) and/or GM1 (0.30 mg/kg). Behavioral and biochemical analyses were conducted 1 month after the infusion procedures. Our results showed that GM1 treatment prevented Aβ-induced cognitive deficit, corroborating its neuroprotective function. Aβ impaired Na,K-ATPase and increase AChE activities in hippocampus and cortex, respectively. GM1, in turn, has partially prevented Aβ-induced alteration on Na,K-ATPase, though with no impact on AChE activity. Aβ caused a decrease in antioxidant defense, specifically in hippocampus, an effect that was prevented by GM1 treatment. GM1, both in cortex and hippocampus, was able to increase antioxidant scavenge capacity. Our results suggest that Aβ-triggered cognitive deficit involves region-specific alterations on Na,K-ATPase and AChE activities, and that GM1 neuroprotection involves modulation of Na,K-ATPase, maybe by its antioxidant properties. Although extrapolation from animal findings is difficult, it is conceivable that GM1 could play an important role in AD treatment. [ABSTRACT FROM AUTHOR]

mong the many glycoconjugates contributing to the sugar code, gangliosides have drawn special attention owing to their predominance as the major sialoglycoconjugate category within the nervous system. However, their occurrence, albeit at lower levels, appears ubiquitous in vertebrate cells and even some invertebrate tissues. Now that over 100 gangliosides have been structurally characterized, their diverse physiological functions constitute a remaining enigma. This has been especially true of GM1, for which a surprising array of functions has already been revealed. Our current research has focused on two areas of GM1 function: (a) signaling induced in neural and immune cells by cross-linking of GM1 in the plasma membrane that leads to activation of TRPC5 (transient receptor potiential, canonical form 5) channels, a process important in neuritogenesis and autoimmune suppression; (b) activation by GM1 of a sodium-calcium exchanger (NCX) in the inner membrane of the nuclear envelope (NE) with resulting modulation of nuclear and cellular calcium. The latter has a role in maintaining neuronal viability, loss of which renders neurons vulnerable to Ca overload. Pathological manifestations in mutant mice and their cultured neurons lacking GM1 have shown dramatic rescue with a membrane permeable derivative of GM1 that enters the nucleus and restores NCX activity. Nuclear function of GM1 is related to the presence of neuraminidase in the NE, an enzyme that generates GM1 through hydrolysis of GD1a. A different isoform of this enzyme was found in each of the two membranes of the NE. [ABSTRACT FROM AUTHOR]

It is generally believed that molecular mimicry between bacterial lipooligosaccharide (LOS) and nerve glycolipids may play an important pathogenic role in immune-mediated peripheral neuropathy. One of the putative infectious agents is Campylobacter jejuni ( C. jejuni). To elucidate the structural basis for the molecular mimicry, we investigated the structure of the lipooligosaccharide (LOS) fraction of C. jejuni, strain HS19, and found that it includes at least two components, characterized as fast-and slow-moving bands (LF and LS) by thin-layer chromatography as revealed by cholera toxin B subunit (Ctxb) overlay. Structural analysis of the oligosaccharide portion of LS established that it had the following structure: Gal-GalNAc-(NeuAc)Gal-Hep-(Glc;PO3H)Hep-Kdo. The GM1-like epitope was validated by a terminal tetrasaccharide unit within this structure. On the other hand, analysis of LF revealed an entirely different structure: 1, 4′-bisphosphoryl glucosamine disaccharide N, N’-acylated by 3-(2-hydroxytetracosanoyloxy)octadecanoic acid at 2- and 2′-positions, which is consistent with that of lipid A. No GM1-like epitope was observed in LF. Both LS and LF interacted with Ctxb as demonstrated by TLC-overlay and sucrose density gradient centrifugation. Surprisingly, LF does not have the basic GM1 structure for interacting with Ctxb. Instead, the affinity of LF to Ctxb required that one or both of the phosphate groups be present in the glucosamine disaccharide residue because after alkaline phosphatase treatment the dephosphorylated LF was unable to bind to Ctxb. We conclude that LS is likely the component contributing to GM1-mimicry in autoimmune peripheral neuropathy and that the role of LF is not clear but may be associated with the initial activation of autoreactive T cells. [ABSTRACT FROM AUTHOR]

Gangliosides, a heterogeneous family of glycosphingolipids abundant in the brain, have been shown to affect neuronal plasticity during development, adulthood and aging. This review will examine old and recent evidence that exogenous gangliosides and in particular GM1, the prototype member of this family, exhibit multimodal neurotrophic effects. Since these compounds are a potential therapeutic tool for the treatment of various forms of acute or chronic neurodegenerative diseases, understanding the dynamic interplay of gangliosides and neuronal cells is essential in the effort to cure neurological disorders. Focus will be given to the novel and provocative hypothesis that gangliosides’ neuroprotective properties may derive from their ability to mimic endogenous neurotrophic factors. [ABSTRACT FROM AUTHOR]

Gangliosides protect cerebellar granule cells from excitotoxicity; however, their mechanism of action remains to be fully characterized. GM1 ganglioside has been shown to activate Trk, the tyrosine kinase receptor implicated in the neuroprotective properties of the neurotrophins. In these studies, we used primary cultures of cerebellar granule cells to determine whether gangliosides exert neuroprotective effect via the activation of Trk receptors. We first examined the relative potency of the neurotrophins, brain derived neurotrophic factor (BDNF), neurotrophin-3 and nerve growth factor to prevent glutamate-mediated apoptosis. BDNF was the only neurotrophin that elicited a complete neuronal protection against glutamate. GM1 and its semisynthetic compound LIGA20 also prevented glutamate toxicity, however, LIGA20 was more potent than GM1. Both LIGA20 and BDNF blocked glutamate-mediated activation of caspase-3 and consequently apoptosis; however, the anticaspase-3 activity was seen only when these compounds were added to the cultures several hours before glutamate, suggesting that LIGA20 and BDNF share an identical molecular mechanism. To test this hypothesis, we compared the ability of LIGA20 and BDNF to activate TrkB. Both compounds elicited a similar time-dependent increase in Trk tyrosine phosphorylation. Moreover, the neuroprotective effect of BDNF and LIGA20 was abolished in neurons exposed to the Trk tyrosine kinase inhibitor k252a, demonstrating a relationship between neuroprotection and activation of Trk receptors. Our data suggest that by activating the Trk neurotrophin receptors, gangliosides may be used as neuroprotective agents. [ABSTRACT FROM AUTHOR]

Haloperidol, a typical antipsychotic drug, causes an increase in the mean percentage of synapses within the striatum containing a discontinuous, or perforated, postsynaptic density (PSD) following 1 month of treatment (Meshul et al. 1994). This effect is not observed with the atypical antipsychotic drug, clozapine, following subchronic administration (Meshul et al. 1992a). This morphological change is also associated with an increase in the density of dopamine D receptors. The synapses containing the perforated PSD are asymmetrical and the nerve terminals contain the neurotransmitter, glutamate, as demonstrated by immunocytochemistry. We have also shown that subchronic treatment with haloperidol (0.5 mg/kg per day, 30 days) results in a decrease in the density of glutamate immunoreactivity within asymmetric nerve terminals associated with perforated and non-perforated PSDs (Meshul and Tan 1994). This could be due to an increase in glutamate release, perhaps due to activation of corticostriatal synapses. Agnati et al. (1983a) reported that administration of GM1 ganglioside blocks the increase in dopamine D receptors following haloperidol treatment. GM1 has also been shown to attenuate the release of glutamate (Nicoletti et al. 1989). In order to determine if similar treatment with ganglioside could block the haloperidol-induced ultrastructural changes noted above, rats were coadministered GM1 (10 mg/kg per day) and haloperidol (0.5 mg/kg per day) for 30 days. We report that GM1 blocked the haloperidol-induced increase in striatal asymmetric synapses containing a perforated PSD, but had no effect on the increase in dopamine D receptors or the decrease in nerve terminal glutamate immunoreactivity. GM1, either alone or co-administered with haloperidol, also caused a small, but significant, increase in the density of all asymmetric synapses within the striatum. It is possible that the effect of GM1 in attenuating the haloperidol-induced change in glutamate synapses with perforated PSDs is primarily postsynaptic, since GM1 did not block the change in density of glutamate immunoreactivity within asymmetric nerve terminals. [ABSTRACT FROM AUTHOR]

Groups of C57BL/6 mice were injected intraperitoneally with GM1 monosialoganglioside at different ages during development and subsequently tested for the retention of an inhibitory avoidance task 24 h after training. Results show improvements in inhibitory avoidance retention according to the age of the animals, the doses of GM1 used and the length of treatment. The effective doses ranged from 20 mg/kg for all age groups after 7 days treatment to 280 mg/kg for 6- and 7-week old animals after pre-trial treatment. Six- and 7-week-old mice are more sensitive to GM1 treatment than 5-week-old animals and, with decreasing lengths of treatment, increasing doses of GM1 are needed to improve the performance of the animals. These findings show that short treatment durations can be effective in improving inhibitory avoidance retention as long as the doses of GM1 administered are increased and that animals are more sensitive to the treatment when they are 6 or 7 weeks of age than when they are 5 weeks old. [ABSTRACT FROM AUTHOR]

To investigate the 3-dimensional outgrowth of ganglion cells of normal and regenerating goldfish retina, retinal explants were cultured in a serum free 3-D fibrin matrix. Daily applications of exogenous gangliosides (GM1), injected either intraocularly (i.o.) or intraperitoneally (i.p.) had no significant effect on the sprouting activity of retinal explants prepared from lesion-activated goldfish whose corresponding optic nerve had been transected. However, in normal, unlesioned animals, a local i.o. injection of GM1 or mixed gangliosides led to a significant enhancement of the basal retinal sprouting activity as compared to controls, which were injected with a 0.9% NaCl solution. This ganglioside related stimulation was maximal after i.o. injection of low concentrations (3 μg/eye), didn't occur at high concentration (30 μg/eye) and was similar to the response obtained after i.o. injection of NGF or insulin. I.o. injected phospholipids had no or a slightly inhibitory effect on the sprouting activity as compared to NaCl controls. Daily in vivo i.o. injections of the monoclonal antibody Q211, specifically recognizing c-pathway polysialogangliosides, led to a dose dependent inhibition of the in vitro sprouting of goldfish retina explants. In summary, these data suggest an involvement of gangliosides in the complex process of induction of neuronal sprouting. [ABSTRACT FROM AUTHOR]

Since exogenous gangliosides are known to promote neuritogenesis, the incorporation of exogenous GM1 into neuroblastoma membranes was examined. Neuro-2A cells, synchronized in the G1/G0 phase, were suspended in HEPES buffered saline containing 10 M [H]GM1, and membrane incorporation was measured as radioactivity remaining with the cell pellet following incubation with serum-containing medium and trypsin. Calcium ion (0.01 to 10 mM) reduced incorporation of exogenous GM1, due to its interaction with GM1 micelles in solution. When cells were treated with proteases prior to incubation with GM1, the inhibitory effect of Ca was lost and total incorporation into membranes was lowered by approximately one order of magnitude. Pretreatment of cells with 0.05% trypsin resulted in an inhibition of GM1 incorporation within 5 minutes. When trypsinized cells were resuspended in complete growth medium, the cells recovered the ability to incorporate GM1 with time, and this paralleled labeling of cellular protein with [H]leucine. The role of membrane protein in the incorporation of exogenous GM1 could not be explained by the lytic release of cytosolic transfer proteins nor the artifactual coating of the cell surface by serum proteins. These results suggest that the incorporation of exogenous gangliosides into cellular membrane lipid bilayers cannot be fully explained by considerations of lipophilicity alone, and leads us to propose that initial recognition by membrane protein(s) is necessary. [ABSTRACT FROM AUTHOR]

Effects of the mono- and tetra-sialogangliosides, GM1 and GQ1b, on long-term potentiation (LTP) were investigated in the CA1 neurons of guinea-pig hippocampal slices. The magnitude of LTP induced by a strong tetanus (100 Hz, 100 pulses) was not significantly affected by application of either ganglioside. In contrast, when LTP was induced by a weak tetanus (100 Hz, 4 pulses), a significantly greater LTP was induced in the presence of either ganglioside. Similarly, when slices were incubated in low-Ca2+ (1.0–1.1 mM) medium for more than 2 h, the LTP was usually small or absent, but showed a significant increase in amplitude of population spike (A-PS) when the slices were incubated with either GM1 or GQ1b (4–5 µg/ml). In addition, the application of GQ1b (4 µg/ml) reversed the blocking effect of an NMDA-receptor antagonist, APP-5 (10 µM), on the induction of LTP and resulted in forming LTP. Based on these findings, we conclude that GM1 and GQ1b exert positive modulatory effects on the induction of LTP in hippocampal CA1 neurons and suggest that GM1 and GQ1b may participate in the induction of LTP as donors of Ca2+ ions. [ABSTRACT FROM AUTHOR]

The effects of GM1 monosialoganglioside pretreatment on brain damage resulting from soman-induced seizure activity were examined in this study. Male Sprague-Dawley rats were infused with GM1 via an osmotic minipump connected through a permanent cannula implanted intracerebroventricularly and challenged with soman (83 μg/kg, i.e., 1.25 × LD50) 4 d after initiation of GM1 infusion. Electrocorticographic recordings were monitored via indwelling cortical electrodes. Twenty-seven hours after soman administration, anesthetized rats were euthanized via transcardial perfusion with buffered paraformaldehyde. Brains were processed for hematoxylin and eosin (H&E), cresyl violet (CV), and acetylcholinesterase (AChE) histochemistry, and glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2) immunohistochemistry. All soman-challenged rats not infused with GM1 ( n=14) developed status epilepticus (SE). GM1-infused, soman-challenged rats ( n=11) showed initial signs of seizures; however, only five developed SE. The remaining six recovered and had no brain damage. In addition, the latter group showed a significantly higher residual AChE reactivity in the basolateral amygdala compared to rats that developed SE. Quantitative image analysis of MAP2-immunostained brain sections from the five GM1-infused rats that developed SE showed a 85.9±14.1% reduction in cross-sectional area of necrosis in the piriform cortex when compared to the somanchallenged rats that were not infused with GM1. This was paralleled by a pronounced decrease in morphological evidence of damage on H&E and CV-stained serial sections. Considerable brain region/treatment group variability was seen with GFAP immunostaining. The present findings demonstrate that GM1 pretreatment interferes with the development of SE and significantly alleviates brain damage resulting from soman-induced seizures. [ABSTRACT FROM AUTHOR]

Several lines of evidence suggest that gangliosides may play a role in the regulation of growth in many cell types. Here we describe the effects on growth of two different cell lines by the addition of two different chemicals which have been reported to elevate the cellular ganglioside content through different mechanisms. Growth of neuroblastoma (Neuro 2a) cells in medium containing fetal bovine serum was inhibited in a dose-dependent fashion by both exogenous GM1 ganglioside and NeuAc2en, an inhibitor of sialidase activity. In contrast, growth of glioma cells (U-1242 MG) was not affected by exogenous GM1 or NeuAc2en in the presence of as little as 1% calf serum. However, NeuAc2en inhibited growth of U-1242 MG cells stimulated by platelet-derived growth factor in serum-free medium. These results demonstrate that the growth inhibitory effects of ganglioside on U-1242 MG but not Neuro 2a cells can be counteracted by serum, suggesting that the mechanisms through which gangliosides affect cell growth may be different for different growth factors and cell types. [ABSTRACT FROM AUTHOR]

The effects of basic fibroblast growth factor (bFGF) and ganglioside GM1 (GM1) were evaluated alone and simultaneously in two types of experiments. First, the neuronal survival of primary culture neurons from fetal rat brain was measured. Then, performance on radial maze task in adult male rats following bilateral partial Fimbria-Fornix transections (F-F lesion) was tested. In primary culture neurons, bFGF (1-10 ng/ml) supported the neuronal survival from three regions (hippocampus, cortex and septum) of embryonic rat brain. However, GM1 (0.1-10 μg/ml) did not support the neuronal survival from any regions. Survival of cultured neurons was not supported by addition of 0.1 ng/ml bFGF, but when bFGF (0.1 ng/ml) and GM1 (0.1, 1 μg/ml) were given to the cultured neurons simultaneously, the number of surviving neurons increased significantly. In the eight-arm radial maze task, where only the same four arms were baited, F-F lesion produced substantial memory impairment. In this task, administration of bFGF (10 μg/ml) or GMl (1 mg/ml) alone did not produce any effects. However, when they were given simultaneously, the number of working memory errors decreased significantly, in spite of no amelioration for hippocampal choline acetyl transferase (ChAT) depletion. These findings indicate that actions of bFGF may be potentiated by the addition of GM1 in both primary neuronal cultures and radial maze task performance. These results suggest that the combination of bFGF and GM1 may synergistically improve spatial memory deficits. [ABSTRACT FROM AUTHOR]