Abnormal growth of the corticospinal axons into the lumbar spinal cord of the hyt/hyt mouse with congenital hypothyroidism

Jung Yu C. Hsu, Stuart A. Stein, Xiao Ming Xu

Research output: Contribution to journalArticle

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Abstract

Thyroid hormone defficiency 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.

Original languageEnglish (US)
Pages (from-to)3126-3139
Number of pages14
JournalJournal of Neuroscience Research
Volume86
Issue number14
DOIs
StatePublished - Dec 8 2008

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Keywords

  • GAP-43
  • Growth cone
  • Myelination
  • NCAM
  • Thyroid hormone

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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