Widespread Expression of Erythropoietin Receptor in Brain and Its Induction by Injury View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-01

AUTHORS

Christoph Ott, Henrik Martens, Imam Hassouna, Barbara Oliveira, Christian Erck, Maria-Patapia Zafeiriou, Ulla-Kaisa Peteri, Dörte Hesse, Simone Gerhart, Bekir Altas, Tekla Kolbow, Herbert Stadler, Hiroshi Kawabe, Wolfram-Hubertus Zimmermann, Klaus-Armin Nave, Walter Schulz-Schaeffer, Olaf Jahn, Hannelore Ehrenreich

ABSTRACT

Erythropoietin (EPO) exerts potent neuroprotective, neuroregenerative and procognitive functions. However, unequivocal demonstration of erythropoietin receptor (EPOR) expression in brain cells has remained difficult since previously available anti-EPOR antibodies (EPOR-AB) were unspecific. We report here a new, highly specific, polyclonal rabbit EPOR-AB directed against different epitopes in the cytoplasmic tail of human and murine EPOR and its characterization by mass spectrometric analysis of immuno-precipitated endogenous EPOR, Western blotting, immunostaining and flow cytometry. Among others, we applied genetic strategies including overexpression, Lentivirus-mediated conditional knockout of EpoR and tagged proteins, both on cultured cells and tissue sections, as well as intracortical implantation of EPOR-transduced cells to verify specificity. We show examples of EPOR expression in neurons, oligodendroglia, astrocytes and microglia. Employing this new EPOR-AB with double-labeling strategies, we demonstrate membrane expression of EPOR as well as its localization in intracellular compartments such as the Golgi apparatus. Moreover, we show injury-induced expression of EPOR. In mice, a stereotactically applied stab wound to the motor cortex leads to distinct EpoR expression by reactive GFAP-expressing cells in the lesion vicinity. In a patient suffering from epilepsy, neurons and oligodendrocytes of the hippocampus strongly express EPOR. To conclude, this new analytical tool will allow neuroscientists to pinpoint EPOR expression in cells of the nervous system and to better understand its role in healthy conditions, including brain development, as well as under pathological circumstances, such as upregulation upon distress and injury. More... »

PAGES

803-815

Identifiers

URI

http://scigraph.springernature.com/pub.10.2119/molmed.2015.00192

DOI

http://dx.doi.org/10.2119/molmed.2015.00192

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1068965790

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26349059


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