Erythropoietin receptor expression is concordant with erythropoietin but not with common beta chain expression in the rat brain throughout the life span

  • Sanchez P
  • Navarro F
  • Fares R
 et al. 
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Abstract

Brain effects of erythropoietin (Epo) are proposed to involve a heteromeric receptor comprising the classical Epo receptor (Epo-R) and the common beta chain (betac). However, data documenting the pattern of betac gene expression in the healthy brain, in comparison with that of the Epo-R gene, are still lacking. The present study is the first to investigate at the same time betac, Epo-R, and Epo gene expression within different rat brain areas throughout the life span, from neonatal to elderly stages, using quantitative RT-PCR for transcripts. Corresponding proteins were localized by using immunohistochemistry. We demonstrate that the betac transcript level does not correlate with that of Epo-R or Epo, whereas the Epo-R transcript level strongly correlates with that of Epo throughout the life span in all brain structures analyzed. Both Epo and Epo-R were detected primarily in neurons. In the hippocampus, the greatest Epo-R mRNA levels were measured during the early postnatal period and in middle-aged rats, associated with an intense neuronal immunolabeling. Conversely, betac protein was barely detectable in the brain at all ages, even in neurons expressing high levels of Epo-R. Finally, betac transcript could not be detected in PC12 cells, even after nerve growth factor-induced neuritogenesis, which is a condition that dramatically enhances Epo-R transcript level. Altogether, our data suggest that most neurons are likely to express high levels of Epo-R but low, if not null, levels of betac. Given that Epo protects extended populations of neurons after injury, a yet-to-be-identified receptor heterocomplex including Epo-R may exist in the large population of brain neurons that does not express betac.

Author-supplied keywords

  • Aging/metabolism
  • Analysis of Variance
  • Animals
  • Astrocytes/metabolism
  • Brain/*growth & development/*metabolism
  • Erythropoietin/*metabolism
  • Gene Expression
  • Immunohistochemistry
  • Male
  • Microglia/metabolism
  • Neurites/metabolism
  • Neurons/metabolism
  • PC12 Cells
  • RNA, Messenger/metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Erythropoietin/*metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

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Authors

  • P E Sanchez

  • F P Navarro

  • R P Fares

  • J Nadam

  • B Georges

  • C Moulin

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