Immunohistochemical localization of erythropoietin and its receptor in the developing human brain

Sandra E. Juul, Anthony T. Yachnis, Amyn Mohammed Rojiani, Robert D. Christensen

Research output: Contribution to journalArticle

171 Citations (Scopus)

Abstract

We have previously shown erythropoietin (Epo) and its receptor (Epo-R) to be present in the fetal human central nervous system (CNS), and Epo to be present in the spinal fluid of normal preterm and term infants. To investigate the cellular specificities and developmental patterns of expression of these polypeptides in the human brain-areas that have not been well researched we designed the following study. Human brains ranging in maturity from 5 weeks post-conception to adult were preserved at the time of elective abortion, surgical removal (tubal pregnancy, or removal for temporal lobe epilepsy), or autopsy. Immunohistochemistry was used to localize Epo and Epo-R reactivity in brains of different stages of development. Astrocytes, neurons, and microglia were identified in sequential tissue sections by specific antibodies. At 5 to 6 weeks post-conception, both Epo and Epo-R localized to cells in the periventricular germinal zone. At 10 weeks post- conception, Epo immunoreactivity was present throughout the cortical wall, with the most intense immunoreactivity present in the ventricular and subventricular zones. Epo-R, in contrast, was localized primarily to the subventricular zone, with little staining evident in the ventricular zone. In late fetal brains, Epo-R reactivity was most prominent in astrocytic cells, although modest reactivity was observed in certain neuron populations. In contrast, Epo staining localized primarily to neurons in fetal brains, although a subpopulation of astrocytes was also immunoreactive. In postnatal brains, both astrocyte and neuron populations were immunoreactive with antibodies to Epo-R and Epo. From these results it is clear that Epo and its receptor are present in the developing human brain as early as 5 weeks post- conception, and each protein shows a specific distribution that changes with development. We speculate that Epo is important in neurodevelopment, and that it also plays a role in brain homeostasis later in life, functioning in an autocrine or paracrine manner.

Original languageEnglish (US)
Pages (from-to)148-158
Number of pages11
JournalPediatric and Developmental Pathology
Volume2
Issue number2
DOIs
StatePublished - Mar 1 1999

Fingerprint

Erythropoietin Receptors
Erythropoietin
Brain
Astrocytes
Neurons
Lateral Ventricles
Staining and Labeling
Tubal Pregnancy
Temporal Lobe Epilepsy
Antibodies
Microglia
Premature Infants
Population
Autopsy

Keywords

  • Erythropoietin
  • Erythropoietin receptor
  • Neurodevelopment
  • Neuron

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine

Cite this

Immunohistochemical localization of erythropoietin and its receptor in the developing human brain. / Juul, Sandra E.; Yachnis, Anthony T.; Rojiani, Amyn Mohammed; Christensen, Robert D.

In: Pediatric and Developmental Pathology, Vol. 2, No. 2, 01.03.1999, p. 148-158.

Research output: Contribution to journalArticle

Juul, Sandra E. ; Yachnis, Anthony T. ; Rojiani, Amyn Mohammed ; Christensen, Robert D. / Immunohistochemical localization of erythropoietin and its receptor in the developing human brain. In: Pediatric and Developmental Pathology. 1999 ; Vol. 2, No. 2. pp. 148-158.
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