Abnormal growth of the corticospinal axons into the lumbar spinal cord of the hyt/hyt mouse with congenital hypothyroidism.
Thyroid hormone deficiency may cause severe neurological disorders resulting from developmental deficits of the central nervous system. The mutant hyt/hyt mouse, characterized by fetal-onset, life-long hypothyroidism resulting from a point mutation of the thyroid-stimulating hormone receptor of the thyroid gland, displays a variety of abnormalities in motor behavior that are likely associated with dysfunctions of specific brain regions and a defective corticospinal tract (CST). To test the hypothesis that fetal and neonatal hypothyroidism cause abnormal CST development, the growth of the CST was investigated in hypothyroid hyt/hyt mice and their euthyroid progenitors, the BALB/cByJ mice. Anterograde labeling with biotinylated dextran amine demonstrated a decrease in the number of CST axons in the hyt/hyt mouse at the first lumbar level at postnatal day (P) 10. After retrograde tracing with fast blue (FB), fewer FB-labeled neurons were found in the motor cortex, the red nucleus, and the lateral vestibular nucleus of the hyt/hyt mouse. At the fourth lumbar level, the hyt/hyt mouse also showed smaller CST cross-sectional areas and significantly lower numbers of unmyelinated axons, myelinated axons, and growth cones within the CST during postnatal development. At P10, the hyt/hyt mouse demonstrated significantly lower immunoreactivity of embryonic neural cell adhesion molecule in the CST at the seventh cervical level, whereas the expression of growth-associated protein 43 remained unchanged. Our study demonstrated an abnormal development of the CST in the hyt/hyt mouse, manifested by reduced axon quantity and retarded growth pattern at the lumbar spinal cord.
Hsu
Jung-Yu C
JY
Department of Anatomy and Neurobiology, Saint Louis University School of Medicine, St Louis, MO, USA. jungyu.hsu@gmail.com
Stein
Stuart A
SA
Xu
Xiao-Ming
XM
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D003409:Congenital Hypothyroidism / Q000473:pathology*; D004195:Disease Models, Animal; D019922:GAP-43 Protein / Q000378:metabolism; D020439:Growth Cones / Q000473:pathology; D007150:Immunohistochemistry; D008161:Lumbosacral Region; D051379:Mice; D008817:Mice, Mutant Strains; D046529:Microscopy, Electron, Transmission; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D011712:Pyramidal Tracts / Q000378:metabolism / Q000473:pathology*
D019922:GAP-43 Protein; D019006:Neural Cell Adhesion Molecules