Thyroid hormone regulates oligodendrocyte accumulation in developing rat brain white matter tracts.
Thyroid hormone (TH) is necessary for normal axonal myelination. Myelin basic protein (MBP) is a structural protein essential for myelin function. In this study, we demonstrate that perinatal hypothyroidism regulates MBP mRNA levels via indirect mechanisms. We observed decreased MBP mRNA accumulation in the hypothyroid rat brain at postnatal (PN) d 10 and 50. Acute TH replacement did not rescue hypothyroid MBP mRNA levels at PN5, 10, or 50. TH is necessary for normal intrahemispheric commissure development including the anterior commissure (AC) and the corpus callosum (CC). We determined that perinatal hypothyroidism decreases AC area and cellularity in the developing rat brain by PN10 and 50. In the developing CC, hypothyroidism initially increases area and cellularity by PN5, but then ultimately decreases area and cellularity by PN50. MBP-expressing oligodendrocytes are a recognized target of TH and are responsible for myelination within intrahemispheric commissures. We found that hypothyroidism reduces the number of mature oligodendrocytes within both the AC and CC. This reduction is noted at PN5, 10, and 50 in the AC and by PN10 and 50 in the CC. Together, these data suggest that TH regulates MBP mRNA levels through indirect mechanisms. These data demonstrate the complex mechanisms whereby TH regulates myelination in the developing brain.
Schoonover
Christopher M
CM
College of Pharmacy, Duluth, 354 Kirby Plaza, 1208 Kirby Drive, Duluth, Minnesota 55812-3095, USA.
Seibel
Melissa M
MM
Jolson
Dawn M
DM
Stack
Mary Jo
MJ
Rahman
Rounak J
RJ
Jones
Sidney A
SA
Mariash
Cary N
CN
Anderson
Grant W
GW
D000818:Animals; D002452:Cell Count; D003337:Corpus Callosum / Q000166:cytology* / Q000254:growth & development / Q000502:physiology; D007037:Hypothyroidism / Q000503:physiopathology*; D004676:Myelin Basic Protein / Q000235:genetics; D009186:Myelin Sheath / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000502:physiology*
D004676:Myelin Basic Protein; D012333:RNA, Messenger; D013963:Thyroid Hormones