Analysis of EphA5 receptor in the developing rat brain: an in vivo study in congenital hypothyroidism model

Eur J Pediatr. 2013 Aug;172(8):1077-83. doi: 10.1007/s00431-013-2008-5. Epub 2013 May 1.

Abstract

The EphA5 receptor has recently been known to play an important role in the initiation of the early phase of synaptogenesis, during which irreparable harm would be done to the developing brain in the absence of sufficient thyroid hormone (TH). In the present article, we aimed to analyze the characteristics of EphA5 receptor expression in the brain of congenital hypothyroid rats. The results showed that the levels of the EphA5 receptor were downregulated by TH deficiency in the developing rat brain with remarkable spatial and temporal characteristics. In the hypothyroid rats, the mRNA and protein levels of EphA5 receptor decreased significantly in the hippocampus (27.92-53.26%), cerebral cortex (12.52-47.16%), and cerebellum (8.72-31.69%) compared with those in the normal rats from postnatal day 0 (P0) to P21 (p < 0.01). The expression of EphA5 receptor was highest and declined most as much as 53% in the hippocampus with TH deficiency. At P7, the EphA5 receptor decreased most prominently during all the observed time point.

Conclusion: The EphA5 receptor plays actively in the brain development in congenital hypothyroid rats. Our study highlights the high expression of EphA5 receptor protein in hippocampus and dramatic changes at P7 in condition of TH deficiency, which may provide important basis for further investigations in manipulating congenital hypothyroidism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antithyroid Agents
  • Brain / growth & development
  • Brain / metabolism*
  • Congenital Hypothyroidism / genetics
  • Congenital Hypothyroidism / metabolism*
  • Disease Models, Animal
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression
  • Hypothyroidism / chemically induced*
  • Hypothyroidism / metabolism
  • Male
  • Methimazole
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Receptor, EphA5 / genetics
  • Receptor, EphA5 / metabolism*
  • Thyroid Hormones / metabolism*

Substances

  • Antithyroid Agents
  • RNA, Messenger
  • Thyroid Hormones
  • Methimazole
  • Receptor, EphA5