methimazole and Demyelinating-Diseases

Thyroid hormone (T3) deficiency impairs the development of the CNS, particularly myelination. We have previously described an increase in the frequency of morphological abnormalities in the central myelin sheath in a hypothyroidism model, which reinforced the hypothesis of a role for T3 in myelin compaction. However, there are no data concerning the cellular distribution of myelin proteins in hypothyroid animals. In the present work, we describe the distribution of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), myelin basic protein (MBP) and proteolipid protein (PLP) throughout the central myelin sheath of a hypothyroidism model. We used euthyroid and hypothyroid adult rats at 90 days of age. In order to induce hypothyroid status, animals received 0.02% methimazol from the 19th gestation day onwards. After perfusion with a fixative mixture, small pieces of corpus callosum were obtained, dehydrated and embedded in LR White resin. Ultrathin sections were immunoreacted, using specific antibodies revealed by a secondary antibody coupled to colloidal gold particles of 10nm. Gold particle density per region of myelin sheath for each one of these proteins was obtained. In normal animals, CNPase, PLP and MBP were identified in sites that had already been described in previous studies. In hypothyroid animals, CNPase was identified in the region corresponding to compact lamellae, which normally does not contain this protein, while, in this same region, PLP and MBP immunolabeling were decreased. These results suggest that thyroid hormone deficiency impairs the distribution of the major oligodendrocyte/myelin markers. This effect may justify the reduction in myelin sheath compaction previously demonstrated in a similar model of hypothyroidism.

Topics: 2',3'-Cyclic-Nucleotide Phosphodiesterases; Animals; Antithyroid Agents; Biomarkers; Cell Membrane; Corpus Callosum; Demyelinating Diseases; Hypothyroidism; Methimazole; Microscopy, Immunoelectron; Myelin Basic Protein; Myelin Proteins; Myelin Proteolipid Protein; Myelin Sheath; Oligodendroglia; Rats; Rats, Wistar

We describe a case of concomitant Graves' disease and demyelination, with optic neuritis and cerebellar dysfunction, in an adolescent girl. Autoimmune thyroid disease with encephalopathy is the hallmark of Hashimoto's encephalopathy, linking thyroid and central nervous system dysfunction. However, to our knowledge, Graves' disease has not been previously reported in association with clinically isolated demyelinating disease in childhood.

Topics: Antithyroid Agents; Autoantigens; Brain; Child; Cluster Analysis; Demyelinating Diseases; Female; Graves Disease; Humans; Magnetic Resonance Imaging; Methimazole; Thyroid Gland