Effect Of Monosialoganglioside GM1 Research Articles

Effect of monosialoganglioside GM1 on cardiopulmonary bypass-induced inflammatory response in rats

Objective To investigate the effect of monosialoganglioside GM1 on cardiopulmonary bypass (CPB)-induced inflammatory response in rats.Methods Twenty-four adult male Sprague-Dawley rats,weighing 350-450 g,were randomly divided into 3 groups (n =8 each):sham operation group (group S),group CPB and CPB + GMi group (group G).GM1 20 mg/kg was added to the priming solution in group G.While the equal volume of normal saline was given in group CPB.Blood samples were collected from the jugular vein at 3 h after termination of CPB for determination of plasma concentrations of neuron-specific enolase (NSE) and S-100β protein (by ELISA) and tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) (by radioimmunoassay).The hippocampi were isolated to detect the expression of hippocampal matrix metalloproteinase-9 (MMP-9) and IL-10 and NF-κB activity in hippocampal tissues by Western blot.Results Compared with group S,the plasma concentrations of NSE,S-100β protein,TNF-α and IL-6 and NF-κB activity were significantly increased,the expression of MMP-9 was up-regulated,and the expression of IL-10 was down-regulated in groups CPB and G (P ＜ 0.05).Compared with group CPB,the plasma concentrations of NSE,S-100β protein,TNF-α and IL-6 and NF-κB activity were significantly decreased,the expression of MMP-9 was down-regulated,and the expression of IL-10 was upregulated in group G (P ＜ 0.05).Conclusion The mechanism by which GM1 reduces the CPB-induced brain damage may be related to reduction of the central and systemic inflammatory response in rats. Key words: G(M1) Ganglioside; Extracorporeal circulation ; Brain injuries; Systemic inflammatory response syndrome

Atomic Force Microscopy Study of Ganglioside GM1 Concentration Effect on Lateral Phase Separation of Sphingomyelin/Dioleoylphosphatidylcholine/Cholesterol Bilayers

The effect of monosialoganglioside GM1 (GM1) concentration on the lateral phase separation in the sphingomyelin/1,2-dioleoyl-sn-glycero-3-phosphocholine/cholesterol (SM/DOPC/Chol) bilayers was studied by using atomic force microscopy. The results show that, with the increase of GM1 mol fraction (x), the dominant composition of liquid-ordered (L(o)) domains changes from SM to SM/GM1 and finally to GM1. Meanwhile, the decrease of domain area (A) of the L(o) phase with the increase of x follows a scaling law of A ∼ x(-3/2), for x > 0.005, indicating that the domain growth is pinned with high GM1 concentration. Results of in situ experiments of GM1 insertion into SM/DOPC/cholesterol bilayers further supported our observations.

Effects of monosialoganglioside GM1 on scopolamine-induced amnesia.

Effects of monosialoganglioside GM1 on scopolamine-induced amnesia.

The Role of Striatal Glutamatergic System in Haloperidol-Induced Dopamine Receptor Supersensitivity and Effects of Monosialoganglioside GM1

The mechanism underlying the action of ganglioside GM1 on the increase of haloperidol-induced dopamine receptor supersensitivity was studied using the method of chemically stimulated ( 3H)-d-aspartate release in rat striatal slices. After a 3-week chronic haloperidol treatment the transmitter release was reduced by about 30%, with a further reduction to 40% when GM1 was applied chronically as well. This suggests that the downregulation of the glutamatergic system by chronic haloperidol treatment is potentiated by gangliosides. The acute effect of gangliosides on the stimulated ( 3H)-d-aspartate release from striatal slices was tested by adding GM1 to the superfusion medium. When given at a concentration of 10 24 M, GM1 did not alter the amino acid release itself. GM1 did, however, reduce the haloperidol-enhanced ( 3H)-d-aspartate release to control levels and elevated the glutamate-stimulated ( 3H)-d-aspartate release. Binding experiments indicate that gangliosides do not directly interact with glutamate or dopamine receptors. The data are discussed in view of earlier findings that GM1 potentiates the behavioral supersensitivity following chronic haloperidol treatment without directly altering dopamine receptor supersensitivity.

Potentiation of nerve growth factor-induced alterations in cholinergic fibre length and presynaptic terminal size in cortex of lesioned rats by the monosialoganglioside GM1

The effect of monosialoganglioside GM1 and/or nerve growth factor treatment on the cholinergic innervation of the rat cortex was studied using both light- and electron-microscopic techniques assisted by image analysis. Adult male Wistar rats were unilaterally decorticated and received continuous infusions, via minipump, of vehicle, GM1 (1.5 mg/day) and/or nerve growth factor (12 μg/day) into the cerebroventricular space. Treatments were initiated immediately post-lesion and ended after seven days. Thirty days post-lesion (i.e. 23 days after the end of drug administration) brains were processed for choline acetyltransferase immunocytochemistry for either light- or electron-microscopic analysis. At this timepoint choline acetyltransferase-immunoreactive neurons in the ipsilateral nucleus basalis magnocellularis were significantly reduced in size especially in the mid portion of this nucleus, in lesion vehicle-treated rats. Moreover, decreases in choline acetyltransferase immunoreactive fibre length (ranging from 31 to 50%) and varicosity number (ranging from 26 to 39%) occurred in all cortical layers within a portion of the remaining cortex of these animals. Monosialoganglioside GM1 or nerve growth factor treatment equally attenuated deficits in nucleus basalis magnocellularis cell size and cortical choline acetyltransferase immunoreactive fibre length. However, nerve growth factor, but not monosialoganglioside GM1 treatment also increased choline acetyltransferase-immunoreactive varicosity number above control levels. In lesioned rats which received both nerve growth factor and the monosialoganglioside GM1, the mean cross-sectional area of nucleus basalis magnocellularis cholinergic neurons did not differ significantly from control values. By contrast, cortical choline acetyltransferase-immunoreactive fibre length and varicosity number were significantly increased above control values and that induced by nerve growth factor treatment alone. Quantitative electron-microscopic analysis showed that cholinergic boutons in cortical layer V were considerably shrunken in lesioned vehicle-treated rats and that GM1 treatment failed to significantly attenuate this deficit. However, exogenous nerve growth factor provoked a significant increase (35% above control values) in cortical cholinergic presynaptic terminal size which was even further augmented by concurrent GM1 treatment (69% above control values). This trophic factor-induced increase in bouton size was confirmed using serial electron microscopy and computer-assisted three-dimen-sional reconstruction of the cholinergic varicosities. The number of synaptic contacts in cortical layer V was also found to be significantly reduced (45% of control values) in lesioned vehicle-treated rats but was maintained at control levels by exogenous GM1 treatment. In addition, a significant increase (95% above control levels) in the number of choline acetyltransferase-immunoreactive boutons with synaptic differentiations was noted in lesioned nerve growth factor-treated rats. Concurrent GM1 and nerve growth factor treatment did not cause a further increase in synaptic number. Cortical cholinergic innervation and the size of choline acetyltransferase-immunoreactive nucleus basalis magnocellularis neurons were not altered in unlesioned rats by GM1, nerve growth factor or nerve growth factor and GM1 treatment. These results demonstrate that GM1 can attenuate deficits in cortical cholinergic innervation following injury and can further augment nerve growth factor induced synaptic remodelling in the injured adult rat brain.

Inhibition of high affinity choline uptake in the rat brain by neurotoxins: Effect of monosialoganglioside GM1

Mustard derivatives of ethyl-choline and hemicholinium-3 have been suggested as possible specific cholinergic neurotoxins. In this study a structural analog of hemicholinium-3, a,a′-bis[di(2-chloroethyl)amino]-4,4′-2-biacetophenone (toxin 7), was added to synaptosomes prepared from the cortex, striatum or hippocampus of rat brain. Synaptosomal high affinity choline uptake (HACU) was significantly decreased in a dose-dependent manner by addition of toxin 7, while synaptosomal uptake of GABA or dopamine was not changed. Incubation of cortical synaptosomes with the monosialoganglioside GM1 prevented the decrease in HACU seen following administration of toxin 7. This preventative effect of GM1 was greater if GM1 was added prior to or concomitant with toxin 7, than if GM1 was added following toxin 7. Two newly synthesized hemicholinium-3 analogs, 4-[3′-di(2-chloroethyl)aminopropionyl] biphenyl (toxin 5) and 4-[3′-di(2-bromoethyl)aminopropionyl]biphenyl (toxin 6) caused a large decrease in HACU when added to cortical synaptosomes, this decrease was significantly greater than that seen with the same dose of toxin 7 or ethyl-choline aziridinium (AF64A). Ultrastructural changes in the synaptosomal membrane following incubation with toxin 7 or toxin 7 with GM1 were examined by electron microscopy. Development of a compound which is both a potent neurotoxin, and is specific for cholinergic neurons will allow new insights into the normal function of the cholinergic system in the CNS and provide animal models of disease states in which cholinergic degeneration is an important element.