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Biomedical subjects

A Gorio

Publications and source records attributed to A Gorio.

At least 91 records · Page 5Linked to original sources
PubMed1984

GM1 micelles modify the transport properties of the ionophore gramicidin D in artificial planar bilayers.

We have analyzed the effects induced in different phospholipid planar bilayers by monosialoganglioside micelles containing the ionophore gramicidin D. The membrane conductance increases after the addition of GM1 micelles at various ionophore/ganglioside ratios. We believe this fact may be ascribed to gramicidin molecules that incorporate into the bilayer together with gangliosides. In the presence of micelles the mean lifetime and the amplitude of the gramicidin single channel did not present relevant modifications when dioleoylphosphatidylcholine or phosphatidylserine were used to form the bilayer. Calcium proved to trigger the interaction between phosphatidylethanolamine membranes and GM1 micelles containing gramicidin. In this case the ionic pore presents a longer lifetime and a lower amplitude with respect to pure gramicidin. We suggest that different properties developed by gramicidin may depend on structural organization of gangliosides when incorporated into the phospholipid bilayer.

Biophysical Phenomena↗
PubMed1984

Effects of GM1 ganglioside on developing and mature serotonin and noradrenaline neurons lesioned by selective neurotoxins.

The effect of exogenous GM1 ganglioside on selective neurotoxin-induced lesions of serotonin (5-HT) and noradrenaline (NA) neurons in both the central and peripheral nervous systems has been investigated in developing and adult rats and mice by employing neuro- and histochemical techniques. 5,7-Dihydroxytryptamine (5,7-HT) was used to lesion 5-HT neurons, and 6-hydroxydopamine (6-OH-DA) was used to lesion NA neurons. In most lesion models investigated the neurotoxin causes primarily an axonal nerve terminal damage without notably affecting the perikarya. There was no evidence indicating that GM1 interferes with the primary and direct neurodegenerative actions of 5,7-HT or 6-OH-DA on 5-HT and NA nerve terminals, respectively. In all lesion models GM1 had in the chronic stage a counteracting effect on the neurotoxin-induced nerve terminal lesion or enhanced regrowth. The present results are compatible with the view that GM1 has a regrowth-stimulating effect and/or protective actions against secondary retrograde degeneration following the initial nerve terminal lesion induced by the neurotoxin.

5,7-Dihydroxytryptamine↗
PubMed1984

Gangliosides' dual mode of action: a working hypothesis.

Using in vitro preparations, we have tested the hypothesis that gangliosides, and more specifically GM1, may prevent progressive neural damage following a trauma by means of complex intracellular mechanisms that might be triggered originally by ganglioside interaction with neuronal membranes. We have recently shown that 2-hr ganglioside incubation in vitro stimulates the membrane Na/K pump in neuromuscular preparations. However, 5-6-hr incubation or in vivo treatment for 3 days with a daily injection of gangliosides at a dose of 1 or 10 mg/kg prevents the depolarization that normally occurs after several hours of exposure to K+-free solutions. In such undepolarized muscles, the electrogenic Na+/K+ pump does not seem to be activated. Hippocampal slices subjected to hypoxia undergo depolarization, which is reversed after oxygen readmission. The recovery phase is characterized by a huge hyperpolarization, probably reflecting electrogenic pump activity. In control preparations the depolarization occurs after 3.15 +/- 0.4 min and has a value of 48.7 +/- 5.7 mV; GM1 treatment for at least 4-5 hr increases the latency to 7.3 +/- 2.3 min, and the depolarization is reduced to 31.8 +/- 4.5 mV. This protective effect is accompanied by a reduced hyperpolarization in treated preparations. The ionic studies performed on neuromuscular preparations indicate that the protective effect may not be solely dependent on K+ leakage; however, the experiments are not conclusive and must be repeated with more direct methods. The results obtained indicate a dual mode of action for gangliosides. The early one seems characterized by membrane-enzyme activation, perhaps in relationship to their incorporation in the membrane, which could be compatible with previously described effects, such as enhancement of neuronal sprouting and neuritogenesis. The late one, occurring 4-5 hr after ganglioside addition in vitro, might reflect intracellular events and be compatible with the protective action exhibited by gangliosides against neural damage.

Animals↗
PubMed1984

Ganglioside treatment of genetic and alloxan-induced diabetic neuropathy.

Peripheral neuropathy is a common complication of diabetes. Using the mutant diabetic mouse C57BL/ks (db/db) and alloxan-treated rats, 30 days after intoxication, we investigated development and treatment with gangliosides of such a disease. The db/db mouse develops a neuropathy characterized by a loss in conduction velocity shown as early as 80-90 days after birth and maintained throughout life. At later stages (5-6 months of age) there is a drop in slow transport and myelin particle density. These changes are correlated by a lack of response to insulin treatment, which, prior to this stage, is capable of improving nerve conduction velocity (NCV). On the other hand gangliosides became effective, improving NCV, myelin particle density and sensory perception (auditory deficit) at 5 months of age in the db/db mouse. We presume that this differential neuronal response to insulin and gangliosides indicates a change of the neuropathy from a metabolic stage to neuronal. Alloxan induced diabetic neuropathy is treatable with gangliosides even 30 days after intoxication.

Acetylcholinesterase↗
PubMed1984

Effect of GM1 ganglioside on neonatally neurotoxin induced degeneration of serotonin neurons in the rat brain.

The effect of exogenous GM1 ganglioside on the 5,7-dihydroxytryptamine (5,7-HT; a selective serotonin neurotoxin) induced alteration of the postnatal development of central 5-hydroxytryptamine (5-HT; serotonin) neurons has been investigated using neuro-chemical and immunocytochemical techniques. Neonatal 5,7-HT (50 mg/kg s.c.) treatment is known to lead to a marked and a permanent degeneration of distant 5-HT nerve terminal projections (e.g. in cerebral cortex, hippocampus and spinal cord), while projections close to the 5-HT perikarya in the mesencephalon and pons-medulla increase their nerve density. These regional alterations are reflected by decreases and increases, respectively, of endogenous 5-HT, [3H]5-HT uptake in vitro and number of 5-HT nerve terminals demonstrated by immunocytochemistry. Treatment of newborn rats with GM1 (4 X 30 mg/kg s.c.; 24 h interval) had no significant effect on the postnatal development of 5-HT neurons. GM1 administration had furthermore no effect on the 5,7-HT induced alteration of the regional 5-HT levels and [3H]5-HT uptake in the cerebral cortex acutely, indicating that GM1 did not significantly interfere with the primary neurodegenerative actions of 5,7-HT. At the age of 1 month a clear counteracting effect of GM1 was observed, in particular of the 5,7-HT induced 5-HT denervations. The 5-HT levels in the frontal and occipital cortex were reduced to 25 and 20% of control after 5,7-HT alone, while these values were 70 and 40%, respectively, after 5,7-HT and GM1 treatment. A similar antagonizing effect of GM1 was found in the frontal cortex when measuring [3H]5-HT uptake. GM1 treatment also caused a minor reduction of the 5,7-HT induced increase of the 5-HT levels in striatum and mesencephalon. Quantitation of 5-HT nerve terminal density in sections processed for 5-HT immunocytochemistry using an automatic image analysis system showed markedly more nerve terminals in the frontal and occipital cortex after 5,7-HT + GM1 compared to 5,7-HT treatment alone. Minor counteracting effects of GM1 were noted in the hippocampus and spinal cord (thoracic-lumbar) as evaluated by chemical 5-HT assay, although substantial counteracting effects were observed locally in these areas by quantitative immunocytochemistry.(ABSTRACT TRUNCATED AT 400 WORDS)

5,7-Dihydroxytryptamine↗
PubMed1984

GM1 ganglioside enhances regrowth of noradrenaline nerve terminals in rat cerebral cortex lesioned by the neurotoxin 6-hydroxydopamine.

The effect of exogenous GM1 ganglioside on selectively noradrenaline-denervated rat cerebral cortex was investigated by measuring the spatial distribution of endogenous noradrenaline levels and by fluorescence histochemical analysis. A local noradrenaline denervation was produced by intracortical infusion of the selective catecholamine neurotoxin 6-hydroxydopamine for 3 or 7 days. The neurotoxin infusion caused an almost complete noradrenaline denervation in a restricted area around the infusion point as reflected by an almost complete long-term disappearance of noradrenaline nerve terminals and reduction of noradrenaline levels. There was with time a slow recovery of the levels, most likely related to a spontaneous noradrenaline nerve terminal regeneration. Post-treatment for 1 week with GM1 had very small effects on the 6-hydroxydopamine-induced reduction of the noradrenaline levels, while pretreatment with GM1 for 3 days before the neurotoxin infusion and continuing the GM1 administration for another 7-14 days significantly enhanced noradrenaline recovery, as observed both bio- and histochemically. GM1 had no effect on the 6-hydroxydopamine-induced noradrenaline depletion acutely, indicating that GM1 does not interfere with the direct neurotoxic actions of 6-hydroxydopamine. The present results thus indicate that exogenous GM1 enhances regrowth of noradrenaline nerve terminals which may be due to a regrowth stimulatory effect (regeneration/collateral sprouting) and/or related to protective actions of GM1 against retrograde degeneration of noradrenaline axons following the neurotoxin-induced lesion.

Adrenergic Fibers↗
PubMed1984

Development of diabetic neuropathy in the C57BL/Ks (db/db) mouse and its treatment with gangliosides.

We studied the development of diabetic neuropathy and its treatment with gangliosides using the C57BL/Ks mouse. The results of axonal morphometry showed the presence of a progressive axonal atrophy which was maximal at 180 days of age. To 400 days of age there was no longer any significant difference, perhaps due to aging processes. Nerve conduction velocity changed significantly from the early days of life. Thirty-day treatment with gangliosides significantly improved nerve conduction velocity and axonal morphometry at 180 and 280 days of life. No effect was observed with treatments at 30 or 60 days. It was previously shown that the early phase of the C57BL/Ks mouse neuropathy was reversed by insulin, whereas the late phase (180 days) was not. We showed elsewhere that at 180 days of age in the C57BL/Ks mouse there was a drastic decrease in slow transport of AChE (G1 and G2 molecular forms) indicating a shift in neuronal metabolism and suggesting that the disease was then more intrinsically neuronal. Using the suggestion of Robertson and Sima (Diabetes 29: 60-67, 1980) we label the first phase of the neuropathy "metabolic" (treatable with insulin) and the second phase "neuronal" (treatable with gangliosides). This "neuronal" phase could be related to the degenerative stage of human diabetic neuropathy.

Animals↗
PubMed1984

Different populations of GABAergic neurons in the visual cortex and hippocampus of cat contain somatostatin- or cholecystokinin-immunoreactive material.

The coexistence of gamma-aminobutyric acid (GABA), glutamate decarboxylase (GAD), and cholecystokinin (CCK)- or somatostatin-immunoreactive material in the same neurons was studied in the hippocampus and visual cortex of the cat. One-micrometer-thick serial sections of the same neuron were reacted to reveal different antigens by the unlabeled antibody enzyme method. All CCK- and somatostatin-immunoreactive neurons in the cortex and all CCK-immunoreactive and the majority of somatostatin-immunoreactive neurons in the hippocampus that could be examined in serial sections were also immunoreactive for GABA. In neurons that were immunoreactive for GAD it was often possible to demonstrate immunoreactivity for one of the peptides as well as for GABA. GABA-immunoreactive neurons, as revealed by an antiserum to GABA, were present in all layers of the cortex and hippocampus, and their shape, size, and distribution were similar to GAD-immunoreactive neurons. All GAD-immunoreactive neurons were also positive for GABA, but the latter staining revealed additional neurons. CCK/GABA- and somatostatin/GABA-immunoreactive neurons were present mainly in layers II and upper III and in layers V and VI in the visual cortex. CCK/GABA-immunoreactive neurons were most frequently present in the strata oriens, pyramidale, and moleculare of the hippocampus and in the polymorph cell layer of the dentate gyrus. Somatostatin/GABA-immunoreactive neurons were localized mainly in the stratum oriens and in the hilus of the fascia dentata. The two peptides could not be found in the same neuron. The majority of neurons that were GABA immunoreactive did not stain for either peptide. The presence of CCK- and somatostatin-immunoreactive material in GABAergic cortical neurons raises the possibility that neuroactive peptides affect GABAergic neurotransmission.

Animals↗
PubMed1983

Capacitance--voltage relationship in phospholipid bilayers containing gangliosides.

Changes in the position of the minimum of the parabolic capacitance-voltage curve allow the measurement of the amount of ganglioside present in artificial bilayers made with phosphatidylcholine-ganglioside mixtures and asymmetrically shielded with Ca2+. The screening effect of the ionic solution must be considered. With ganglioside/phospholipid molar ratios of up to 15%, all glycolipids can be found at the membrane surfaces.

Gangliosides↗
PubMed1983

A new type of specific interneuron in the monkey hippocampus forming synapses exclusively with the axon initial segments of pyramidal cells.

By means of Golgi staining and gold-toning, we have found an interneuron in the pyramidal cell layer of the hippocampus which forms synapses exclusively on the axon initial segments of pyramidal neurons. An individual initial segment receives up to 30 symmetrical synapses from one axo-axonic cell. Each axo-axonic cell is in synaptic contact with the axon initial segments of several hundred pyramidal neurons. The interneuron is thus ideally situated to synchronize the output of a large population of pyramidal cells and so might be involved in the generation of rhythmic activity and in epileptogenesis.

Animals↗
PubMed1983

Functional and morphological abnormalities induced by ouabain intoxication of the rabbit retina.

Several researchers have recently used an intravitreal ouabain injection to induce a suitable model of experimental retinopathy and optic neuropathy in various animals. Ouabain administration into the vitreous body of rabbit causes an irreversible degeneration of the retinal layers and consequently of the optic nerve. The degeneration is proportional to the amount of injected drug. Electroretinographic recordings (ERG) show that these structural abnormalities are related to an inhibition of the electric retinal activity as the dose-dependent reduction of ERG waves amplitude has shown. Moreover, ERG and visual evoked responses (VER) measured at the same time evidence that the intravitreal injection of 1.7 nmol ouabain may block the impulse conduction along the optic nerve. This can be proved by the fact that 90 min after an ouabain injection VER disappears, while ERG is only partially reduced. These results are correlated with both morphological observation and autoradiographic studies on 3H-ouabain distribution in different retinal layers.

Animals↗
PubMed1983

Monosialoganglioside (GM1) treatment of ouabain-induced retinopathy in the rabbit.

The mammalian retina is markedly influenced by cardiac glycosides. When nanomolar concentrations of ouabain are intravitreously injected into the rabbit, the visually evoked response completely disappears within 90 min, while scotopic ERG recordings show a remarkably decreased amplitude of the principal waves. When 33 nmol/kg monosialoganglioside are injected intravenously 30 min before topical intoxication, this functional impairment is significantly reduced. The electroretinographic response shows a limited amplitude reduction, while the cortical potential never disappears completely. Histological observations of intoxicated retinas show that a degenerative process begins in photoreceptor outer segment 24 h after the intravitreal ouabain injection. Presently, this process involves both the outer and inner nuclear layers and, finally, the ganglion cell layer. Comparing the intoxicated treated and untreated retinas, no difference is found in the degenerative pattern of the two groups. Autoradiographic studies are also reported to correlate the protective effect of monoganglioside (GM1) on this toxic retinopathy with its preferential accumulation in different retinal tissues.

Animals↗
PubMed1983

Axonal transport of acetylcholinesterase in the diabetic mutant mouse.

During the development of diabetic neuropathy in the mouse C57BL/Ks (db/db), the axonal transport of AChE molecular forms was tested in the sciatic nerve, by measuring the accumulation of enzyme activity in front of a nerve transection. No alteration of the fast flow rate of G4 and A12 molecular forms was found until 220 days of age. On the other hand, a reduced flow rate of G1 and G2 molecular forms, probably conveyed by slow axoplasmic flow, was noticed in the late phase of diabetic neuropathy. This result is consistent with the view that axonal dwindling could be related to disturbances of slow axonal transport and that the reduction in conduction velocity, observed at an earlier stage, may be due to other causes.

Acetylcholinesterase↗
PubMed1983

Gangliosides enhance neurite outgrowth in PC12 cells.

Gangliosides are surface membrane components that have been suggested to play a significant role in the regulation of many cellular events including neuronal differentiation, growth and regeneration. We have chosen PC12 cell as a model system to study the influence of exogenously added glycosphyngolipids on in vitro differentiation and regeneration. A mixture of bovine brain gangliosides, (GM1 21%, GD1a 39.7%, GD1b 16% and GT 19%) or purified GM1 and GT respectively were added to culture media containing NGF on plating day and their effect was monitored on alternate days starting on day 5. The degree and rate of fiber outgrowth was significantly enhanced by media containing gangliosides at a concentration of 10(-6), 10(-7) M when serum was left out and 10(-3), 10(-4) M when serum was added to the culture medium. The stimulating ganglioside action required the presence of NGF to induce neurite outgrowth. However, binding studies indicated that exogenous gangliosides do not affect NGF binding to PC12 cells, therefore their stimulatory action may be separated from the interaction between NGF and its receptors. Subculturing of NGF-treated cells for 10 days demonstrated that gangliosides treatment also enhanced the NGF stimulated regeneration of neurites. Gangliosides may be incorporated at the level of cell surface, thereby affecting and facilitating membrane phenomena involved in neurite outgrowth.

Animals↗