The effect of the ganglioside GM1 on neuronal plasticity.
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Animals↗
Biomedical subjects
G Toffano
Publications and source records attributed to G Toffano.
Apomorphine-induced inhibition of histamine release in rat peritoneal mast cells.
The apomorphine-induced inhibition of histamine release in rat peritoneal mast cells was studied by means of secretagogues stimulating different pathways of mast cell activation. Apomorphine inhibited the mast cell response to all releasing agents (lysophosphatidylserine plus nerve growth factor, compound 48/80, substance P, ATP, tetradecanoylphorbolacetate, melittin). The IC50 ranged from 4 microM to 24 microM at concentrations of secretagogues releasing 30-50% of mast cell histamine. However, the potency of the drug decreased at higher secretagogue concentrations. Mast cells, pretreated with apomorphine and washed, released little histamine upon stimulation. The secretory response could be partially restored on increasing the concentration of secretagogues. The results suggest that apomorphine affects a regulatory step controlling the terminal sequence of mast cell secretory activity. As indicated by the reduced potency of the drug, the control by the apomorphine-sensitive reaction loses efficiency under conditions of massive histamine release.
Adenosine Triphosphate↗
A correlation analysis of the regional distribution of central enkephalin and beta-endorphin immunoreactive terminals and of opiate receptors in adult and old male rats. Evidence for the existence of two main types of communication in the central nervous system: the volume transmission and the wiring transmission.
By means of semiquantitative immunocytochemistry and quantitative receptor autoradiography a correlation analysis has been performed on the pre- and post-synaptic features of enkephalin and beta-endorphin immunoreactive neuron systems of the 3- and 24-month-old male rat. A parallel disappearance of enkephalin- and beta-endorphin-like immunoreactivity and of the density of mu and delta opiate receptors is shown during ageing. Furthermore, the lack of an overall correlation between the amount of pre- and post-synaptic components of the enkephalin and beta-endorphin synapses give evidence for the existence of a volume type of transmission in such systems in the telencephalic, diencephalic and mesencephalic areas analysed.
Age Factors↗
Complement-dependent immune damage to liposomes containing gangliosides.
Rabbit antiserum against mixed beef brain gangliosides served as an excellent source of antibodies to gangliosides GM1, GM3, GD1a, GD1b, and GT1b. Immune potency of antiserum was determined by complement-dependent damage to liposomes containing gangliosides as antigens. Antibody levels in antiserum to mixed gangliosides, when tested against individual gangliosides, were equivalent or superior to the levels obtained by immunization of rabbits with purified individual gangliosides. Naturally occurring antibodies to GM1, GD1b, and GM3 were observed in preimmunization sera. The levels of these natural antibodies, although easily high enough to serve as antiserum sources for liposome assay, were increased substantially following immunization. High titers of antibodies to GM1 and GD1b were observed in certain individual guinea pig sera, and selection of individual non-reacting guinea pig sera was necessary in order to obtain suitable complement sources when testing rabbit antibodies to liposomal GM1 and GD1b. The maximum plateau level of trapped glucose release from liposomes in the presence of saturating levels of antigen, antiserum, and complement was influenced strongly both by the method of removing untrapped glucose during liposome preparation and by the type of ganglioside incorporated into the lipid bilayer.
Animals↗
Molecular specificity of ganglioside effects on neurite regeneration of sensory neurons in vitro.
Highly purified preparations of individual gangliosides have been tested for their ability to modulate the survival and morphological differentiation of embryonic chick dorsal root ganglion neurons. When added at 48 h to established cultures of nerve growth factor (NGF)-dependent neurons, all ganglioside species tested increased the expression of neurofilament protein. Poly- and trisialogangliosides were more effective than di- or monosialogangliosides. In contrast, neither NGF nor an antiserum against NGF influenced neurofilament protein expression over this period of culture. In addition, ganglioside-induced expression of neurofilament protein was not inhibited by the anti-NGF serum.
Animals↗
Effects of neurotoxic and mechanical lesions of the mesostriatal dopamine pathway on striatal polyamine levels in the rat: modulation by chronic ganglioside GM1 treatment.
In male rats, partial hemitransections but not 6-hydroxydopamine (6-OHDA)-induced lesions of the mesostriatal dopamine (DA) pathway produce after 7 days a marked and a modest increase of striatal putrescine and spermidine levels, respectively, on the lesioned side. Following chronic ganglioside GM1 treatment of partially hemitransected rats, an increase of striatal polyamine levels was observed also on the intact side. It is suggested that retrograde cell body changes produced by hemitransection may induce striatal ornithine decarboxylase activity and in this way increase striatal putrescine levels, favoring regenerative mechanisms. The increase of striatal polyamine levels by GM1 treatment on the intact side of both 6-OHDA and mechanically lesioned rats compared with intact unoperated rats may also reflect an increased synthesis of striatal polyamines.
Animals↗
Effects of intracerebral injections of quinolinic acid on serotonergic neurons in the rat brain.
The effects of intrastriatal and intrahippocampal injections of the excitotoxic amino acid, quinolinic acid (QUIN), were examined in the rat using immunohistochemical and neurochemical techniques. Serotonin and 5-hydroxyindoleacetic acid measurements at 90 min, 6 h, 4 and 11 days following QUIN administration revealed highly elevated levels of the metabolite in the injected nuclei, with peak increases occurring after 4 days. Serotonin levels remained largely unchanged over the same time period. Direct visualization of hippocampal serotonergic fibers by immunohistochemistry demonstrated morphological changes (varicosities, swellings) in otherwise undamaged serotonin-positive afferents 4 days following a local QUIN injection. Hippocampal serotonin turnover was assessed at 4 days after an intrahippocampal QUIN-application: following inhibition of aromatic amino acid decarboxylase, the accumulation of 5-hydroxytryptophan was twice as rapid in QUIN-lesioned hippocampi as in controls. Dose-response relationships, examination of brain regions distant from the two injection sites and the temporal sequence of the changes described here suggest a close association between QUIN-induced neuronal degeneration and alterations in the serotonergic system.
Animals↗
Evidence for crossed catecholaminergic nigrostriatal projections by combining wheat germ agglutinin-horseradish peroxidase retrograde transport and tyrosine hydroxylase immunocytochemistry.
After unilateral injections of wheat germ agglutinin-horseradish peroxidase into the rat caudate-putamen, a few retrogradely labeled neurons were found in the contralateral pars compacta of the substantia nigra. These contralaterally projecting nigral cell bodies also immunoreacted positively to a specific tyrosine hydroxylase antiserum. We conclude that crossed catecholaminergic nigrostriatal projections may contribute to the reciprocal regulation exerted by the two nigrostriatal dopaminergic systems.
Animals↗
Synergism between lysophosphatidylserine and the phorbol ester tetradecanoylphorbolacetate in rat mast cells.
In rat peritoneal mast cells tetradecanoylphorbolacetate (TPA) induced a non cytotoxic histamine release in the absence of extracellular calcium. The addition of calcium prevented the TPA effect but micromolar concentrations of lysophosphatidylserine (lysoPS) converted the calcium-induced inhibition into a stimulation. Other lysophospholipids were inactive. In agreement with a mutual influence between lysoPS and TPA, minimal TPA concentrations enhanced the calcium-dependent histamine release induced by lysoPS in the presence of nerve-growth factor. It is proposed that the calcium-dependent pathway promoted by lysoPS and the activation of protein kinase C by TPA act synergically to induce histamine release from mast cells.
Animals↗
Effects of lesions and ganglioside GM1 treatment on striatal polyamine levels and nigral DA neurons. A role of putrescine in the neurotropic activity of gangliosides.
The effects of a partial hemitransection at the meso-diencephalic level, with or without chronic ganglioside GMI treatment, have been evaluated on striatal polyamine levels, 7, 14 and 21 days after lesion, as well as on the ability of the polyamine synthesis inhibitor alpha-difluoromethylornithine (alpha-DFMO) to modulate the protective effects of chronic ganglioside GMI treatment against retrograde degeneration of the nigral dopamine (DA) nerve cell bodies (14 day time interval). The striatal polyamine levels were measured by high pressure liquid chromatography after dansylation of the polyamines. The nigral DA nerve cells were studied by means of tyrosine hydroxylase (TH) immunocytochemistry using the indirect immunoperoxidase technique. Quantitation was performed by means of morphometrical evaluation of the TH immunoreactive area of the substantia nigra. Seven days after partial hemitransection there is a marked increase (above 350%) in striatal putrescine levels, which is not modulated by chronic GMI treatment. This marked increase could, to a large extent, be counteracted by simultaneous treatment with alpha-DFMO, which blocks mainly the synthesis of putrescine. Twenty-one days after lesion chronic GMI treatment could produce an increase in striatal putrescine levels on the intact side and also after this time-interval prevent the reduction of striatal spermine levels. It was also found that simultaneous treatment with alpha-DFMO prevents the development of the protective action of chronic ganglioside GMI treatment against retrograde degeneration of the nigral DA neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effects of ganglioside GM1 treatment on striatal glucose metabolism, blood flow, and protein phosphorylation of the rat.
Effects of ganglioside GM1 administration have been studied in unilaterally partially hemitransected rats on striatal energy metabolism, using the radioactive deoxyglucose (DG) technique, on striatal blood flow, using radiolabelled iodoantipyrine (IAP) as tracer, and on cyclic AMP (cAMP) and Ca2+ induced protein phosphorylation in striatal membranes (P2 fraction). Ganglioside GM1 treatment counteracted the imbalance in striatal energy metabolism, in striatal blood flow, as well as in protein phosphorylation found between the striata of the lesioned and unlesioned side, possibly due to excitatory effects on the lesioned side and inhibitory effects on the unlesioned side. In intact animals, GM1 treatment produced a reduction in cAMP and Ca2+ induced striatal protein phosphorylation. Facilitatory actions of the ganglioside GM1 dominate following a lesion, probably due to its possible function as a modulator of receptors for neuronotrophic factors, leading to restoration of metabolic rate and of cAMP and Ca2+ induced protein phosphorylation in the striatum of the lesioned side. The results emphasize that ganglioside GM1 treatment can restore the metabolism of a partially innervated striatum towards normal, as evaluated both at the level of the entire striatal structure by means of the DG and IAP techniques and at the molecular level by means of studies on the cAMP and Ca2+ induced protein phosphorylation.
Animals↗
Pharmacological effect of phosphatidylserine on age-dependent memory dysfunction.
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Aging↗
Serine phospholipids as endocoids.
Unusual phospholipid effects may occur when their distribution in the membrane is altered or when uncontrolled metabolic reactions yield elevated concentrations of their short lived derivatives. Serine phospholipids are normally buried in the internal side of plasma membrane. Upon exposure to the extracellular environment they elicit a response from selected cell populations. The interaction between these phospholipids and neuroactive compounds in rat peritoneal mast cells may indicate that serine phospholipids have a role in the nervous system during development.
Animals↗
Experimental models of aging and quinolinic acid.
The normal aging process results in many functional deficits in which the central nervous system (CNS) plays a primary role. However, the study of brain aging involves numerous difficulties, including not only the complex anatomical and functional organization of the brain itself, but also because the length of the experiments themselves and experimental costs are often crucial limitations. This highlights an ever increasing need for the development of alternative model systems capable of mimicking at least to some degree the main alterations observed during the normal aging process. A comparative study of electrophysiological and behavioural features in aged rats and in young rats following chronic administration of a naturally occurring brain metabolite, quinolinic acid (QUIN), recently demonstrated to increase in the cerebral cortex of rats as a function of age, is reported. In rats there occurs an age-dependent increase in the number of animals displaying spontaneous asymptomatic spike-wave discharges, associated with impaired performance in the passive avoidance test. Chronic oral administration of QUIN to young rats also results in cortical spiking activity, without any detectable neuronal cell damage at cortical or hippocampal levels, associated with behavioural deficits similar to those observed in old rats. The utilization of young, QUIN-treated animals may thus perhaps offer an alternative model system for the comprehension of the mechanisms involved in some age-related functional impairments.
Aging↗
Serine phospholipids and aging brain.
For many years phospholipids have been studied mainly for their possible use as membrane models or cell-like carriers. Recently, on the basis of the new knowledge on the phospholipid membrane structure and function, a novel interest has arisen on the pharmacological properties of these compounds particularly at cerebral level. In this context particular attention has been devoted to phosphatidylserine (BC-PS), an anionic phospholipid extracted and purified from bovine brain, which in young animals has been shown to modify a number of brain electrophysiological and biochemical parameters.
Aging↗
Chronic GM1 ganglioside treatment reduces dopamine cell body degeneration in the substantia nigra after unilateral hemitransection in rat.
The effect of GM1 ganglioside on the recovery of dopaminergic nigro-striatal neurons was studied in rats after unilateral hemitransection. GM1 treatment partially prevented the decrease of tyrosine hydroxylase (TH) activity caused by hemitransection in the substantia nigra ipsilateral to the lesion. Concomitantly a significant increase of TH-immunoreactivity in the substantia nigra was also detected. In particular, chronic treatment with GM1 prevented the disappearance of TH-positive cell bodies in the substantia nigra and induced the appearance of longer TH-positive dendrites with respect to the saline treatment. These data indicate that GM1 treatment maintains the number of dopaminergic cell bodies in the substantia nigra after hemitransection by protecting against retrograde neuronal degeneration.
Animals↗
Dorsal root ganglia and nerve growth factor: a model for understanding the mechanism of GM1 effects on neuronal repair.
The experimental strategy of adding monosialoganglioside GM1 to a culture medium of fetal chick dorsal root ganglia (DRG) was utilized as a model system in which to examine the potential role of GM1 in modulation of neuronal cell responsiveness to nerve growth factor (NGF). Data indicate that the addition of GM1 to DRG explants or to DRG dissociated neuronal cells in culture enhances NGF-induced neurite outgrowth, neurite complexity, and neuronal cell survival following NGF withdrawal. The GM1 molecule apparently facilitates the acquisition or maintenance of the NGF-induced specific neuronal properties. Results are consistent with the hypothesis that the presence of GM1 molecules on the neuronal cell surface, either endogenous or following stable insertion of exogenous molecules, plays a prominent role in the modulation of functional neuronal cell behavior in response to varying neuronotrophic signals. This may prove to be relevant for the comprehension of GM1 effects on the facilitation of central nervous system repair processes.
Animals↗
The functional recovery of damaged brain: the effect of GM1 monosialoganglioside.
In the present study the topology and the biochemical mechanisms underlying the functional recovery of the dopaminergic nigrostriatal system is further analyzed. Rats with unilateral hemitransection were treated with 30 mg/kg GM1 monosialoganglioside or with its internal ester derivative for different periods of time. GM1 enhances 3H-dopamine uptake in striatal synaptosomes of the lesioned side, and the enhancement of dopamine uptake precedes that of striatal tyrosine hydroxylase activity. The above biochemical effects are accompanied by changes in behavioral- and electrophysiological-related parameters. The effect of GM1 on striatal tyrosine hydroxylase of the lesioned side disappears when the ascending dopaminergic fibers are extensively lesioned. This suggests that the source of regrowing dopaminergic nerve terminals in the striatum of partially lesioned rats resides mainly in the intact axons remaining in the ipsilateral side. When GM1 is injected into partially lesioned rats kept in darkness, no effect on tyrosine hydroxylase activity is observed. This indicates that the mechanism through which GM1 acts involves a normal light-dark cycle.
Animals↗