g(m1)-ganglioside and Brain-Diseases

Multi-modal brain networks characterize the complex connectivities among different brain regions from structure and function aspects, which have been widely used in the analysis of brain diseases. Although many multi-modal brain network fusion methods have been proposed, most of them are unable to effectively extract the spatio-temporal topological characteristics of brain network while fusing different modalities. In this paper, we develop an adaptive multi-channel graph convolution network (GCN) fusion framework with graph contrast learning, which not only can effectively mine both the complementary and discriminative features of multi-modal brain networks, but also capture the dynamic characteristics and the topological structure of brain networks. Specifically, we first divide ROI-based series signals into multiple overlapping time windows, and construct the dynamic brain network representation based on these windows. Second, we adopt adaptive multi-channel GCN to extract the spatial features of the multi-modal brain networks with contrastive constraints, including multi-modal fusion InfoMax and inter-channel InfoMin. These two constraints are designed to extract the complementary information among modalities and specific information within a single modality. Moreover, two stacked long short-term memory units are utilized to capture the temporal information transferring across time windows. Finally, the extracted spatio-temporal features are fused, and multilayer perceptron (MLP) is used to realize multi-modal brain network prediction. The experiment on the epilepsy dataset shows that the proposed method outperforms several state-of-the-art methods in the diagnosis of brain diseases.

Topics: Brain; Brain Diseases; G(M1) Ganglioside; Humans; Learning

GM1 ganglioside (one week each at 10, 5, and 2.5 mg GM1/kg per day, ip) or gradual food restriction leading to a reduction in body weight to 75% of control were tested for their ability to block or reverse histopathologic and behavioral effects of trimethyltin (TMT) poisoning in rats. TMT (a single oral gavage of 6.0 mg TMT HCI/kg body weight) reduced hippocampal weight, decreased hippocampal cell counts, decreased autoshaped learning measures, and suppressed progressive fixed ratio (PFR) lever pressing without affecting stable lever pressing. Neither GM1 nor greater food restriction affected hippocampal weight. Greater food restriction prevented TMT's effects on autoshaping but not on PFR behavior, was without behavioral effects in animals not treated with TMT, and did not affect hippocampal histology. GM1 prevented certain TMT-induced decrements in autoshaping and PFR behavior but also suppressed autoshaping and stimulated stable fixed ratio behavior in animals not treated with TMT. GM1 also reduced hippocampal serotonin concentration, another "lesion-like" change. GM1 blocked TMT-induced hippocampal CA3b cell loss, but did not protect CA3c cells, the main locus of TMT hippocampal damage. The results support the idea that exogenous GM1 is a potent neuroactive agent with complex actions in intact organisms, potentially beneficial and potentially toxic. Like GM1, food restriction induces complex and potentially beneficial effects, but it lacked GM1's biochemical and behavioral "side effects" (i.e. toxicity) in these experiments.

Topics: Animals; Behavior, Animal; Brain Chemistry; Brain Diseases; Conditioning, Operant; Food Deprivation; G(M1) Ganglioside; Hippocampus; Male; Motor Activity; Rats; Reinforcement Schedule; Serotonin; Trimethyltin Compounds

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 micrograms/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 time-point 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 w

Topics: Animals; Brain Diseases; Cerebral Cortex; Choline O-Acetyltransferase; Cholinergic Fibers; Drug Synergism; G(M1) Ganglioside; Image Processing, Computer-Assisted; Male; Microscopy, Electron; Nerve Growth Factors; Presynaptic Terminals; Rats; Rats, Wistar; Receptors, Nerve Growth Factor; Synapses

Eight sooty mangabey monkeys were inoculated intravenously and intradermally with varying doses of Mycobacterium leprae from 4.8 x 10(7) to 4.8 x 10(10). Serum samples were obtained from the animals at intervals of about 3 months for 90 months, and were examined for IgM and IgG antibodies to nerve antigens, including ceramide, galactocerebroside (GC), and asialo-GM1 (AGM1), using an enzyme-linked immunosorbent assay (ELISA). The serological results were then compared with clinical findings, particularly nerve involvement. Of 8 mangabey monkeys inoculated with M. leprae, 7 animals had clinical leprosy; 6 of them had nerve damage, including neurologic deformities in 4 monkeys and nerve enlargement in 2. Median time for the initial signs of leprosy was 10 months postinoculation (p.i.), a range from 4 to 35 months. In contrast, nerve damage was noted rather late, about 35 to 86 months p.i. (median 54 months). The major immunoglobulin class to ceramide, GC, and AGM1 antigens was IgM, and the antibody responses to the nerve antigens appeared from 15 to 63 months p.i. (median 37 months). Antineural antibodies were thus detectable about 18 months (range -2 to 60 months) prior to observable nerve damage. In addition, elevation of antineural antibody levels were predictive of clinical exacerbation of the disease and neuritic damage. This study suggests that antineural antibodies are produced during the course of M. leprae infection and may be indicative of nerve damage, such as neurological deformities or nerve enlargement, in leprosy patients.

Topics: Animals; Autoantigens; Brain Diseases; Ceramides; Cercocebus atys; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Galactosylceramides; Immunoglobulin G; Immunoglobulin M; Leprosy, Lepromatous; Mycobacterium leprae; Nerve Tissue Proteins

Reconstitution of 3- to 4-week-old BALB/c nude (nu/nu) mice with 10(7) syngeneic splenocytes, 48 h before intracerebral inoculation with a temperature-sensitive (ts) mutant of VSV (tsG31 KS5), provided protection from the fatal consequences of clinical disease in 80-90% of the infected animals. Reconstitution of animals with 10(7) splenocytes, first depleted of natural killer (NK) cells with anti-asialo GM1 and complement, also afforded protection against the infectious disease. Depletion of T-lymphocytes with anti-thy-1.2 antibody and complement, however, provided little protection with approximately 40% of the animals succumbing to the virus infection within 30 days post-infection. A single intracerebroventricular injection with 14 pM of beta-endorphin, 24 h prior to viral infection, led to an increased fatality of mice previously reconstituted with T-lymphocytes but not in animals receiving only syngeneic NK cells. The increased fatality caused by the neuropeptide was antagonized by naloxone but not beta-endorphin-(1-27). Separation of splenocyte cell populations by buoyant density centrifugation demonstrated that small race lymphocytes, and not the large granular lymphocytes, were responsible for protection of nude mice from the central nervous system infection with ts-VSV. The beta-endorphin-responsive immune cells were shown to be a minor fraction of the small race T-lymphocyte population that bear the asialo-GM1 marker.

Topics: Animals; beta-Endorphin; Brain Diseases; G(M1) Ganglioside; Glycosphingolipids; Killer Cells, Natural; Mice; Mice, Inbred BALB C; Mice, Nude; T-Lymphocytes; Vesicular stomatitis Indiana virus; Virus Diseases

Monosialoganglioside GM1 prevents excitatory amino acid (EAA)-related neuronal death in cultured central nervous system (CNS) neurons and reduces the severity of acute brain damage in different experimental models of cerebral ischemia. Using a model of brain damage induced by intracerebroventricular administration of N-methyl-D-aspartate (NMDA) in neonate rats, we evaluated whether GM1 is capable of exerting antiexcitotoxic effects following its systemic administration in vivo. Newborn rats subjected to brain damage by NMDA and contemporaneously treated subcutaneously with GM1 showed significantly reduced (i) loss in hemispheric weight, (ii) loss in tissue choline acetyltransferase activity, and (iii) morphological damage in various brain areas. These results indicate that systemic GM1 treatment is efficacious in reducing EAA-related neuronal damage in vivo and suggest that such a phenomenon may underlie its capability to ameliorate neurological outcome following cerebral ischemia.

Topics: Animals; Animals, Newborn; Brain; Brain Diseases; Female; G(M1) Ganglioside; Male; N-Methylaspartate; Rats; Rats, Inbred Strains

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.

Topics: Animals; Brain Diseases; Catalepsy; Corpus Striatum; Dopamine; Dyskinesia, Drug-Induced; G(M1) Ganglioside; Haloperidol; Injections, Intravenous; Male; Mice; Motor Activity; Movement Disorders; MPTP Poisoning; Orientation; Receptors, Dopamine; Receptors, Dopamine D2; Up-Regulation

The administration of GM1 ganglioside, 30 mg/kg per day i.p., begun 3 days prior to an intrastriatal injection of the excitotoxic tryptophan metabolite quinolinic acid (QUIN) and continued for 8-16 days thereafter, significantly decreased QUIN-induced striatal damage, as evaluated by measuring the activity of the marker enzymes, choline acetyltransferase and L-glutamic acid decarboxylase. Since an increased production of QUIN has been demonstrated in Huntington's chorea patients it is possible that repeated GM1 administration could reduce the occurrence of progressive striatal neuronal loss in this neurological disorder.

Topics: Animals; Brain Diseases; Choline O-Acetyltransferase; Corpus Striatum; G(M1) Ganglioside; Glutamate Decarboxylase; Male; Pyridines; Quinolinic Acids; Rats; Rats, Inbred Strains

Mice injected intracerebrally with infectious influenza virus (60 hemagglutinin units) developed lethargy, seizures, comas, and died 2 to 5 days postinfection. As early as 6 h after infection, the cerebrospinal fluid (CSF) in these animals was infiltrated with polymorphonuclear cells, mononuclear leukocytes, and large granular lymphocytes. Potent natural killer (NK) cell activity was observed for both CSF and spleen cell populations over the same period. This NK cell activity correlated with interferon (IFN) levels in the CSF and serum. Treatment of lethally infected mice with either anti-IFN alpha-IFN beta or anti-ganglio-n-tetraoglyceramide antiserum ameliorated the disease, reduced mortality, and effected changes in the relative proportions of inflammatory cell populations infiltrating the CSF. The possible significance of IFN and NK cell activity in the development of this influenza virus-induced encephalopathy is discussed.

Topics: Animals; Brain Diseases; G(M1) Ganglioside; Glycosphingolipids; Immunologic Techniques; Influenza A virus; Interferons; Killer Cells, Natural; Kinetics; Male; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections

In rats with extensive unilateral cortical damage, retrograde effects upon the cholinergic cells of the basal nucleus were observed. Cells of the basal nucleus stained immunocytochemically for choline acetyltransferase were shrunken and choline acetyltransferase enzymatic activity in that region was reduced. Both these effects could be prevented by the administration of the ganglioside GM1.

Topics: Alzheimer Disease; Animals; Basal Ganglia; Brain Diseases; Cerebral Cortex; Choline O-Acetyltransferase; G(M1) Ganglioside; Male; Rats; Rats, Inbred Strains; Substantia Innominata

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.

Topics: Animals; Brain Diseases; Corpus Striatum; Dopamine; Electrophysiology; G(M1) Ganglioside; Gangliosides; Rats; Rats, Inbred Strains; Substantia Nigra; Synaptosomes; Tyrosine 3-Monooxygenase

Topics: Acetylglucosaminidase; Animals; beta-N-Acetylhexosaminidases; Brain; Brain Diseases; G(M1) Ganglioside; G(M2) Activator Protein; Glycoproteins; Glycoside Hydrolases; Glycosphingolipids; Hexosaminidases; Humans; Lysosomes; Proteins; Saposins; Sphingolipid Activator Proteins

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.

Topics: Adrenergic Fibers; Animals; Brain Diseases; Cerebral Cortex; G(M1) Ganglioside; Gangliosides; Hydroxydopamines; Male; Norepinephrine; Oxidopamine; Rats; Rats, Inbred Strains; Synapses

The effect of intramuscular administration of monosialoganglioside (GM1) on postlesion responses of choline acetyltransferase and acetylcholinesterase activity in partially deafferented rat hippocampus was studied at various survival times. Lesions partially destroying the medioventral, septal area, or lesions performed in supracallosal stria including corpus callosum and cingulum evoked cholinergic denervation of the hippocampus, while those made in entorhinal cortex resulted in partial glutamatergic deafferentation. GM1 treatment potentiates the responses of both cholinergic enzymes, independently of whether the partial deafferentation was homo- or heterotypical. These data indicate that GM1 may facilitate the regrowth of new cholinergic nerve terminals. However, an effect on other compensatory processes, especially in the first postoperative period, is also possible.

Topics: Acetylcholinesterase; Afferent Pathways; Animals; Brain Diseases; Choline O-Acetyltransferase; G(M1) Ganglioside; Gangliosides; Hippocampus; Limbic System; Male; Rats; Rats, Inbred Strains

It has been extensively reported that monocular exposure early in life leads to profound alterations in visual cortical areas, where the majority of cells become responsive only to the stimulation of the normal eye. We have investigated a possible effect of the monosialoganglioside internal ester, termed AGF2, on the neuronal cortical plasticity of the kitten's visual cortex following monocular deprivation. Results indicate that in monocularly deprived kittens treated with ganglioside the ocular dominance shift in favor of the normal eye is partially prevented.

Topics: Animals; Brain Diseases; Cats; Functional Laterality; G(M1) Ganglioside; Gangliosides; Sensory Deprivation; Vision, Ocular; Visual Cortex