ganglioside--gd1a and Demyelinating-Diseases

Remyelination failure by oligodendrocytes contributes to the functional impairment that characterizes the demyelinating disease multiple sclerosis (MS). Since incomplete remyelination will irreversibly damage axonal connections, treatments effectively promoting remyelination are pivotal in halting disease progression. Our previous findings suggest that fibronectin aggregates, as an environmental factor, contribute to remyelination failure by perturbing oligodendrocyte progenitor cell (OPC) maturation. Here, we aim at elucidating whether exogenously added gangliosides (i.e., cell surface lipids with a potential to modulate signaling pathways) could counteract fibronectin-mediated inhibition of OPC maturation. Exclusive exposure of rat oligodendrocytes to GD1a, but not other gangliosides, overcomes aggregated fibronectin-induced inhibition of myelin membrane formation,

Topics: Animals; Axons; Cells, Cultured; Cuprizone; Cyclic AMP Response Element-Binding Protein; Cyclic AMP-Dependent Protein Kinases; Demyelinating Diseases; Enzyme Activation; Fibronectins; Gangliosides; Male; Mice; Multiple Sclerosis; Myelin Sheath; Neural Stem Cells; Oligodendroglia; Rats; Signal Transduction

We report a patient with sensorimotor demyelinating neuropathy with high-titer IgM antibody against gangliosides GD1a, GT1b and GM3. The patient was a 65-year-old male who was hospitalized with chief complaints of muscular weakness of all limbs and numbness of the hands and feet. Nerve-conduction studies revealed reduced conduction velocities of the motor nerves with increased temporal dispersion and loss of sensory nerve action potentials. Treatment with steroids was ineffective. IgM antibody against GD1a, GT1b and GM3, which are known to be the ligands for myelin-associated glycoprotein (MAG), might have played a role in the demyelination in this patient by inhibiting adhesion between myelin and axonal membrane.

Topics: Aged; Antibodies; Demyelinating Diseases; G(M3) Ganglioside; Gangliosides; Humans; Immunoglobulin M; Male; Movement; Sensation

High titers of anti-GD1a antibodies have been found in patients with Guillain-Barre syndrome or motor neuropathy. To determine the possible diagnostic relevance of these antibodies, we measured serum anti-GD1a IgG and IgM antibodies by enzyme-linked immunosorbent assay in 195 patients with different motor syndromes and in 335 control subjects. Moderately high antibody titers (1/1,280-1/5,120) were occasionally found in patients with chronic inflammatory demyelinating polyneuropathy (5%), multifocal motor neuropathy (18%), lower motor neuron disease (3.8%), or amyotrophic lateral sclerosis (1.8%) and in immunological control subjects (1.2%), while titers of 1/20,480 or higher were only found in 2 patients with Guillain-Barre syndrome (IgG in both) and 2 with motor neuropathy and IgM lambda monoclonal gammopathy improving with immunotherapy. In both motor neuropathy patients and the Guillain-Barre syndrome patient who were retested during recovery, anti-GD1a titers decreased concomitantly with clinical improvement. High anti-GD1a antibody titers may be found in several motor syndromes but only markedly increased anti-GD1a titers are strictly associated with potentially treatable dysimmune neuropathies.

Topics: Aged; Antibodies; Chromatography, Thin Layer; Demyelinating Diseases; Enzyme-Linked Immunosorbent Assay; Female; Gangliosides; Humans; Immunoglobulin G; Immunoglobulin M; Middle Aged; Neuromuscular Diseases; Peripheral Nervous System Diseases; Polyradiculoneuropathy