Impact of thyroid hormone deficiency on the developing CNS: cerebellar glial and neuronal protein expression in rat neonates exposed to antithyroid drug propylthiouracil.
The developing rat cerebellum is vulnerable to thyroid hormone (TH) deficiency. The present study addresses the molecular mechanisms involved in this response. Specifically, the study focuses on the expression of selected cerebellar proteins that are known to be directly [protein expressing 3-fucosyl-N-acetyl-lactosamine antigen (CD15), neuronal cell adhesion molecule (L1)] or indirectly [glial fibrillary acidic protein (GFAP)], involved in glial-neuronal interactions and thus regulation of cell proliferation and granule cell migration. Cerebellar mass, structure, and protein expression in rat neonates exposed to antithyroid drug propylthiouracil (PTU) from the embryonic day (E) 16 to postnatal day (P) 21 were compared against rat neonates that received replacement of thyroxin (T4) starting on day P1 or untreated controls. Cerebellar proteins were analyzed by quantitative Western blots. PTU-treated rats lagged in growth and showed reduction in cerebellar mass and alterations in cerebellar structure on P15. Daily treatment of neonates with T4 restored normal cerebellum-to-body-mass ratio, cerebellar structure, and cerebellar protein expression. Densitometric analysis of Western blots revealed altered expression of selected proteins in the cerebella of hypothyroid neonates. A decrease of CD15 (46%, p = 0.031) was observed on P10 and was accompanied by a decrease in GFAP expression (64%, p = 0.039). Furthermore, a shift in the developmental GFAP profile was observed in the PTU-treated cerebellum. L1 expression was not significantly affected in the hypothyroid cerebellum. Altered expression of cerebellar proteins is likely to affect cell-cell interactions and consequently cell proliferation and migration and contribute to structural and functional alterations seen in the hypothyroid rat neonates.
Li
Gui-Hua
GH
Department of Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Post
Jennifer
J
Koibuchi
Noriyuki
N
Sajdel-Sulkowska
Elizabeth M
EM
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D013956:Antithyroid Agents / Q000494:pharmacology*; D015153:Blotting, Western / Q000379:methods; D015992:Body Mass Index; D002531:Cerebellum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D016256:Lewis X Antigen / Q000378:metabolism; D008297:Male; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D011247:Pregnancy; D011441:Propylthiouracil / Q000494:pharmacology*; D051381:Rats; D013963:Thyroid Hormones / Q000172:deficiency*
D013956:Antithyroid Agents; D005904:Glial Fibrillary Acidic Protein; D016256:Lewis X Antigen; D039842:Neural Cell Adhesion Molecule L1; D013963:Thyroid Hormones; D011441:Propylthiouracil