i(3)so3-galactosylceramide and Amyotrophic-Lateral-Sclerosis

Our previous lipidomics studies demonstrated elevated sulfatides, plasmalogens, and N-acylphosphatidylserines in the frontal cortex of schizophrenia subjects. These data suggest that there may be an abnormal function of glycosynapses in schizophrenia. We further examined the disease and anatomical specificity of these observations.. We undertook a targeted lipidomics analysis of plasmalogens, sulfatides, and N-acyl-phosphatidylserines in the frontal cortex obtained from schizophrenia, bipolar, and ALS subjects and the cerebellum of schizophrenia subjects.. We demonstrate that sulfatides, plasmalogens, and N-acyl-phosphatidylserines are significantly elevated in the frontal cortex of patients suffering from schizophrenia and bipolar depression but not in ALS patients. These lipids were unchanged in the cerebellum of subjects with schizophrenia.. Our data suggest that dysfunction of oligodendrocyte glycosynapses may be specific to limbic circuits in schizophrenia and that this dysfunction is also detected in bipolar depression, suggesting that these disorders possess several common pathophysiological features.

Topics: Adult; Aged; Aged, 80 and over; Amyotrophic Lateral Sclerosis; Bipolar Disorder; Cerebellum; Female; Frontal Lobe; Humans; Male; Middle Aged; Oligodendroglia; Phosphatidylserines; Plasmalogens; Schizophrenia; Sulfoglycosphingolipids

It is well known that polyneuropathy is associated with monoclonal IgM kappa.. We report the case of a 79-year-old man with lymphoma and motor neuron disease at cervical level simulating amyotrophic lateral sclerosis (ALS). Neurological deficit with inflammatory process evolved within 4 months. Electrophysiological findings showed increased and enlarged muscular potentials with neurogenic patterns. Nerve conduction velocities were normal, with neither multifocal neuropathy nor persistent conduction blocks. Besides mixed cryoglobulinemia type II, antisulfatide antibodies issued from monoclonal IgM were found. They were directed against myelin glycosphingolipids. No antiganglioside GM1 antibodies could be detected. This not only evoked ALS but also proximal motor axonopathy related with monoclonal IgM.. This case suggests that antisulfatide antibodies often present in sensitive demyelinating polyneuropathy could also be involved in lower motor neuron syndrome.

Topics: Aged; Amyotrophic Lateral Sclerosis; Antibodies; Cryoglobulinemia; Diagnosis, Differential; Electromyography; Electrophysiology; Humans; Immunoglobulin kappa-Chains; Immunoglobulin M; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Motor Neuron Disease; Sulfoglycosphingolipids

Immunostaining of human, bovine and rodent unfixed nervous tissue sections was performed in order to characterize the structures recognized by anti-glycolipid antibodies. Four human sera from patients, two with M-IgM and motor neuron syndrome or motor neuropathy and two with motor neuropathy and polyclonal IgG antibody activity against gangliosides (GL; i.e. GM1, GD1b, GD1a), were utilized. Serum from a patient with sensory neuropathy and M-IgM immunoglobulins with antibody activity against sulfatide (SUL) was included in this series. This study shows that polyclonal and monoclonal anti-glycolipid antibodies give three different patterns of staining. The first is cholera toxin-like showing a more restricted neuronal pattern of staining. The second is peanut agglutinin-like, which includes the carbohydrate epitope shared by a group of glycoproteins in the gray and white matter. The third (anti-SUL) gives a preferential myelin staining. However, sera with anti-GM1 and anti-SUL antibodies recognize a number of closely situated determinants in the gray matter of the spinal cord and in the granule cells, while in peripheral nerves or in neuronal cells in culture their binding produces a different pattern (nodes of Ranvier for anti-GL; myelin for anti-SUL). These findings indicate that immunohistochemistry with anti-GL and anti-SUL antibodies may provide information regarding the glycolipid-bearing anatomical structures as target antigens and further substantiate the role of these molecules in the pathogenesis of autoimmune neurological disorders.

Topics: Amyotrophic Lateral Sclerosis; Animals; Antibodies, Monoclonal; Autoantigens; Carbohydrate Sequence; Cattle; Cells, Cultured; Epitopes; Gangliosides; Glycolipids; Humans; Immune Sera; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Motor Neuron Disease; Myelin Sheath; Nervous System; Neurons; Rabbits; Sulfoglycosphingolipids