1. Abnormal growth of the corticospinal axons into the lumbar spinal cord of thehyt/hytmouse with congenital hypothyroidism
- Author
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Jung Yu C. Hsu, Xiao Ming Xu, and Stuart A. Stein
- Subjects
medicine.medical_specialty ,Red nucleus ,Growth Cones ,Central nervous system ,Pyramidal Tracts ,Cell Count ,Biology ,Mice ,Cellular and Molecular Neuroscience ,GAP-43 Protein ,Microscopy, Electron, Transmission ,Internal medicine ,Congenital Hypothyroidism ,medicine ,Animals ,Axon ,Neural Cell Adhesion Molecules ,Lumbosacral Region ,medicine.disease ,Immunohistochemistry ,Retrograde tracing ,Axons ,Mice, Mutant Strains ,Congenital hypothyroidism ,Disease Models, Animal ,Lateral vestibular nucleus ,Endocrinology ,medicine.anatomical_structure ,Corticospinal tract ,Neural cell adhesion molecule ,human activities - Abstract
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.
- Published
- 2008