myelin-basic-protein and Seizures

The pathophysiology of unilateral cortical fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein (MOG)-associated encephalitis with seizures (FLAMES) is unclear. A 26-year-old man was referred because of a seizure. FLAIR showed an increased signal intensity and swelling of the right frontal cortex. His symptoms and imaging abnormalities were improved after intravenous methylprednisolone therapy. MOG antibody was detected both in serum and cerebrospinal fluid (CSF). Therefore, the patient was diagnosed with FLAMES. Myelin basic protein (MBP) was elevated in CSF. The high MBP value in the CSF in the present case suggested that demyelination as well as inflammation can occur in some FLAMES patients.

Topics: Autoantibodies; Encephalitis; Humans; Magnetic Resonance Imaging; Myelin Basic Protein; Myelin-Oligodendrocyte Glycoprotein; Myelitis; Seizures

Tuberous sclerosis is a developmental genetic disorder caused by mutations in TSC1, which results in epilepsy, autism, and intellectual disability. The cause of these neurological deficits remains unresolved. Imaging studies suggest that the thalamus may be affected in tuberous sclerosis patients, but this has not been experimentally interrogated. We hypothesized that thalamic deletion of Tsc1 at distinct stages of mouse brain development would produce differential phenotypes. We show that mosaic Tsc1 deletion within thalamic precursors at embryonic day (E) 12.5 disrupts thalamic circuitry and alters neuronal physiology. Tsc1 deletion at this early stage is unique in causing both seizures and compulsive grooming in adult mice. In contrast, only a subset of these phenotypes occurs when thalamic Tsc1 is deleted at a later embryonic stage. Our findings demonstrate that abnormalities in a discrete population of neurons can cause global brain dysfunction and that phenotype severity depends on developmental timing and degree of genetic mosaicism.

Topics: Animals; Animals, Newborn; Behavior, Animal; Biophysics; Brain Mapping; Cerebral Cortex; DNA-Binding Proteins; Electric Stimulation; Electron Transport Complex IV; Embryo, Mammalian; Female; Gene Expression Regulation, Developmental; Glial Fibrillary Acidic Protein; Green Fluorescent Proteins; Grooming; Hand Strength; Homeodomain Proteins; Hyperalgesia; In Vitro Techniques; Linear Models; Male; Membrane Potentials; Mice; Mice, Transgenic; Myelin Basic Protein; Neural Pathways; Neurons; Nuclear Proteins; Pain Measurement; Patch-Clamp Techniques; Phosphopyruvate Hydratase; Physical Stimulation; Pregnancy; Proteins; RNA, Untranslated; Seizures; Sequence Deletion; Tamoxifen; Thalamus; Tuberous Sclerosis Complex 1 Protein; Tumor Suppressor Proteins; Ubiquitin-Protein Ligases; Vibrissae

Hippocampus learning disturbance is a major symptom of patients with seizure, hence hippocampal dysfunction has essential role in worsening the disease. Hippocampal formation includes neurons and myelinated fibers that are necessary for acquisition and consolidation of memory, long-term potentiation and learning activity. The exact mechanism by which seizure can decrease memory and learning activity of hippocampus remains unknown. In the present study, electrical kindling-induced learning deficit in rats was evaluated by Morris water maze (MWM) test. The hippocampus was removed and changes in neurons and myelin sheaths around hippocampal fibers were investigated using histological and immunohistochemical methods. Demyelination was assessed by luxol fast blue staining, and immunohistological staining of myelin-binding protein (MBP). The TUNEL assay was used for evaluation of neuronal apoptosis and the glial fibriliary acetic protein (GFAP) was used for assessment of inflammatory reaction. The results indicated that electrical kindling of hippocampus could induce deficiency in spatial learning and memory as compared to control group. In addition, electrical kindling caused damage to the myelin sheath around hippocampal fibers and produced vast demyelination. Furthermore, an increase in the number of apoptotic cells in hippocampal slices was observed. In addition, inflammatory response was higher in kindled animals as compared to the control group. The results suggested that the decrease in learning and memory in kindled animals is likely due to demyelination and augmentation in apoptosis rate accompanied by inflammatory reaction in hippocampal neurons of kindled rats.

Topics: Animals; Apoptosis; Avoidance Learning; Demyelinating Diseases; Disease Models, Animal; Electron Transport Complex IV; Excitatory Amino Acid Antagonists; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Hippocampus; Indoles; Ketamine; Kindling, Neurologic; Learning Disabilities; Locomotion; Male; Maze Learning; Myelin Basic Protein; Rats; Rats, Wistar; Reaction Time; Seizures

Salla disease and infantile sialic acid storage disease are autosomal recessive lysosomal storage disorders caused by mutations in the gene encoding sialin, a membrane protein that transports free sialic acid out of the lysosome after it is cleaved from sialoglycoconjugates undergoing degradation. Accumulation of sialic acid in lysosomes defines these disorders, and the clinical phenotype is characterized by neurodevelopmental defects, including severe CNS hypomyelination. In this study, we used a sialin-deficient mouse to address how loss of sialin leads to the defect in myelination. Behavioral analysis of the sialin(-/-) mouse demonstrates poor coordination, seizures, and premature death. Analysis by histology, electron microscopy, and Western blotting reveals a decrease in myelination of the CNS but normal neuronal cytoarchitecture and normal myelination of the PNS. To investigate potential mechanisms underlying CNS hypomyelination, we studied myelination and oligodendrocyte development in optic nerves. We found reduced numbers of myelinated axons in optic nerves from sialin(-/-) mice, but the myelin that was present appeared grossly normal. Migration and density of oligodendrocyte precursor cells were normal; however, a marked decrease in the number of postmitotic oligodendrocytes and an associated increase in the number of apoptotic cells during the later stages of myelinogenesis were observed. These findings suggest that a defect in maturation of cells in the oligodendrocyte lineage leads to increased apoptosis and underlies the myelination defect associated with sialin loss.

Topics: Animals; Apoptosis; Axons; Brain; Cell Count; Cell Movement; Longevity; Mice; Mice, Knockout; Motor Activity; Myelin Basic Protein; Myelin Sheath; Nerve Tissue Proteins; Neurons; Oligodendroglia; Optic Nerve; Organic Anion Transporters; Peripheral Nervous System; Seizures; Spinal Cord; Stem Cells; Symporters; Transcription Factors

Selective depletion of central nervous system norepinephrine (NE) by the neurotoxin 6-hydroxydopamine (6-OHDA) in rats subsequently inoculated with myelin basic protein (MBP) and complete Freund's adjuvant (CFA) produced experimental autoimmune encephalomyelitis (EAE) without the usual expected degree of weakness. The preservation of strength occurred in spite of continued weight loss. Post-decapitation myoclonic convulsive kick latency and kick number, which are known to depend on spinal cord NE, agreed well with the degree of weakness through the clinical disease course. The only difference between EAE groups was that the stronger 6-OHDA pretreated EAE animals did not have an elevated pons-medulla NE compared to saline intracisternal-ventricular (i.c.v.) pretreated controls. We conclude that 6-OHDA can influence the clinical course of weakness by interfering with central noradrenergic activity independent of other features associated with disease in EAE. This effect of 6-OHDA may be exerted through alteration of the blood-spinal cord barrier function and/or central nervous system blood flow.

Topics: Animals; Body Weight; Brain; Catecholamines; Cerebral Ventricles; Cisterna Magna; Decerebrate State; Encephalomyelitis, Autoimmune, Experimental; Freund's Adjuvant; Hydroxydopamines; Injections, Intraventricular; Male; Myelin Basic Protein; Norepinephrine; Oxidopamine; Rats; Rats, Inbred Lew; Seizures

Topics: Animals; Axons; Central Nervous System; Gene Expression Regulation; Genotype; Mice; Mice, Neurologic Mutants; Mice, Transgenic; Myelin Basic Protein; Myelin Sheath; Oligodendroglia; Seizures