Altered CD15 glycolipid expression in the developing rat cerebellum following treatment with antithyroid drug, propylthiouracil.
Thyroid hormone plays an important role during central nervous system (CNS) development. Experimentally-induced perinatal hypothyroid rats show abnormal cerebellar cytoarchitecture, but the underlying mechanism is not fully understood. Altered cell-cell interactions may contribute to such abnormalities, since the expression of NCAM is increased in hypothyroid animals. In the present study, we examined the expression of carbohydrate epitope 3-fucosyl-N-acetyl-lactosamine (CD15 antigen), that can be localized on both astrocytes and neurons in the developing brain, and is considered to play an important role in glial-neuronal interaction and cell migration. Newborn rats were treated with an antithyroid drug, propylthiouracil (PTU) and the CD15 glycolipid levels in the cerebellum were examined by enzyme-linked immunosolvent assay (ELISA) using 7A monoclonal antibody raised against rat forebrain antigen. A transient elevation of CD15 level was observed on postnatal day 10 in PTU-treated animals. Analysis of neutral glycolipids on high performance thin layer chromatography (HPTLC), revealed two distinct immunoreactive bands, corresponding to Fuc-nLc6 and Fuc-nLc4. The Fuc-nLc4 is preferentially increased in the PTU-treated group. These results suggest that a transient increase in CD15 glycoconjugates with isoform-specific manner induced by PTU may contribute to morphological abnormalities in hypothyroid rat cerebellum affecting granule cell migration.
Sajdel-Sulkowska
E M
EM
Department of Psychiatry, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
Koibuchi
N
N
D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D016256:Lewis X Antigen / Q000096:biosynthesis*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011441:Propylthiouracil / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D013956:Antithyroid Agents; D016256:Lewis X Antigen; D011441:Propylthiouracil