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Immunohistochemical localization of erythropoietin and its receptor in the developing human brain
S E Juul1, A T Yachnis, A M Rojiani
1Department of Pediatrics, University of Florida College of Medicine, P.O. Box 100296, JHMHC, Gainesville, FL 32610-0296, USA.
Insights
Erythropoietin (Epo) and its receptor (Epo-R) are present in the developing human brain from 5 weeks post-conception. Their expression patterns change during development, suggesting roles in neurodevelopment and brain homeostasis.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Erythropoietin (Epo) and its receptor (Epo-R) are known to be present in the fetal human central nervous system (CNS).
- Epo has been detected in the spinal fluid of preterm and term infants.
- Limited research exists on the cellular and developmental expression patterns of Epo and Epo-R in the human brain.
Purpose of the Study:
- To investigate the cellular specificities and developmental patterns of Epo and Epo-R expression in the human brain.
- To map the localization of Epo and Epo-R in the developing human brain from early gestation to adulthood.
Main Methods:
- Human brain tissue samples were collected from 5 weeks post-conception to adulthood.
- Immunohistochemistry was employed to localize Epo and Epo-R reactivity.
- Specific antibodies were used to identify astrocytes, neurons, and microglia in sequential tissue sections.
Main Results:
- Epo and Epo-R were detected as early as 5 weeks post-conception in the periventricular germinal zone.
- Epo expression was widespread in the fetal cortical wall, with higher concentrations in ventricular and subventricular zones.
- Epo-R expression was primarily in the subventricular zone in early development, shifting to astrocytes and neurons in later fetal and postnatal stages. Epo predominantly localized to neurons in fetal brains.
Conclusions:
- Epo and Epo-R are present in the developing human brain from very early stages (5 weeks post-conception).
- The distribution of Epo and Epo-R changes significantly throughout brain development.
- These findings suggest a crucial role for Epo in human neurodevelopment and potentially in maintaining brain homeostasis in adulthood.
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.