title: Erythropoietin receptor expression is concordant with erythropoietin but not with common beta chain expression in the rat brain throughout the life span.
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.
authors.affiliation: Université de Lyon, Lyon, France.
authors.forename: Pascal E
authors.initials: PE
authors.lastname: Sanchez
authors.forename: Fabrice P
authors.initials: FP
authors.lastname: Navarro
authors.forename: Raafat P
authors.initials: RP
authors.lastname: Fares
authors.forename: Jérémie
authors.initials: J
authors.lastname: Nadam
authors.forename: Béatrice
authors.initials: B
authors.lastname: Georges
authors.forename: Colette
authors.initials: C
authors.lastname: Moulin
authors.forename: Marion
authors.initials: M
authors.lastname: Le Cavorsin
authors.forename: Chantal
authors.initials: C
authors.lastname: Bonnet
authors.forename: Philippe
authors.initials: P
authors.lastname: Ryvlin
authors.forename: Amor
authors.initials: A
authors.lastname: Belmeguenai
authors.forename: Jacques
authors.initials: J
authors.lastname: Bodennec
authors.forename: Anne
authors.initials: A
authors.lastname: Morales
authors.forename: Laurent
authors.initials: L
authors.lastname: Bezin