Effects of hypothyroidism on expression of CRMP2B and ARPC5 during development of the rat frontal cortex

Int J Biol Sci. 2013;9(2):209-18. doi: 10.7150/ijbs.5646. Epub 2013 Feb 12.

Abstract

Congenital hypothyroidism (CH) can lead to irreversible central nervous system (CNS) damage. However, the pathogenesis of the developmental brain disorders caused by CH has not been completely elucidated. ARPC5 and CRMP2 are closely associated with neurite outgrowth in brain development. Thus, the aim of the present study was to determine whether CRMP2B and ARPC5 expression is altered in the developing cerebral cortex of rats with CH. Control rats and rats with hypothyroidism were sacrificed at birth and at 15 days postpartum. We performed qRT-PCR to detect differences in the crmp2B and arpc5 mRNA expression in the right half of the frontal cortex of these rats. Western blotting was then used to detect differences in CRMP2B and ARPC5 protein expression. Furthermore, immunohistochemical analysis was performed on the left half of the frontal cortex to detect abnormal localization of CRMP2B and ARPC5. Results showed increased expression of the nuclear short isoform of CRMP2B and decreased expression of full-length CRMP2B and ARPC5 in cortical neurons of rats with hypothyroidism. These findings demonstrate that reduced levels of thyroid hormones can inhibit the expression of full-length CRMP2B and ARPC5 and promote nuclear transformation of the short isoform of CRMP2B. CRMP2B and ARPC5 may participate in CNS injury mediated by hypothyroidism by inducing neurite outgrowth inhibition and cytoskeletal protein disorganization.

Keywords: ARPC5; CRMP2B; congenital hypothyroidism; frontal cortex; rat..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / metabolism*
  • Analysis of Variance
  • Animals
  • Blotting, Western
  • Congenital Hypothyroidism / metabolism*
  • DNA Primers / genetics
  • Female
  • Frontal Lobe / growth & development*
  • Frontal Lobe / metabolism
  • Gene Expression Regulation, Developmental / physiology*
  • Intercellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins / metabolism*
  • Neurites / physiology
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thyroid Hormones / metabolism*

Substances

  • ARPC5 protein, rat
  • Actin-Related Protein 2-3 Complex
  • DNA Primers
  • Intercellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Thyroid Hormones
  • collapsin response mediator protein-2