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Revisiting adult neurogenesis and the role of erythropoietin for neuronal and oligodendroglial differentiation in the hippocampus

Please always quote using this URN: urn:nbn:de:bvb:20-opus-186669
  • Recombinant human erythropoietin (EPO) improves cognitive performance in neuropsychiatric diseases ranging from schizophrenia and multiple sclerosis to major depression and bipolar disease. This consistent EPO effect on cognition is independent of its role in hematopoiesis. The cellular mechanisms of action in brain, however, have remained unclear. Here we studied healthy young mice and observed that 3-week EPO administration was associated with an increased number of pyramidal neurons and oligodendrocytes in the hippocampus of similar to 20%.Recombinant human erythropoietin (EPO) improves cognitive performance in neuropsychiatric diseases ranging from schizophrenia and multiple sclerosis to major depression and bipolar disease. This consistent EPO effect on cognition is independent of its role in hematopoiesis. The cellular mechanisms of action in brain, however, have remained unclear. Here we studied healthy young mice and observed that 3-week EPO administration was associated with an increased number of pyramidal neurons and oligodendrocytes in the hippocampus of similar to 20%. Under constant cognitive challenge, neuron numbers remained elevated until >6 months of age. Surprisingly, this increase occurred in absence of altered cell proliferation or apoptosis. After feeding a \(^{15}\)N-leucine diet, we used nanoscopic secondary ion mass spectrometry, and found that in EPO-treated mice, an equivalent number of neurons was defined by elevated \(^{15}\)N-leucine incorporation. In EPO-treated NG2-Cre-ERT2 mice, we confirmed enhanced differentiation of preexisting oligodendrocyte precursors in the absence of elevated DNA synthesis. A corresponding analysis of the neuronal lineage awaits the identification of suitable neuronal markers. In cultured neurospheres, EPO reduced Sox9 and stimulated miR124, associated with advanced neuronal differentiation. We are discussing a resulting working model in which EPO drives the differentiation of non-dividing precursors in both (NG2+) oligodendroglial and neuronal lineages. As endogenous EPO expression is induced by brain injury, such a mechanism of adult neurogenesis may be relevant for central nervous system regeneration.show moreshow less

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Metadaten
Author: I. Hassouna, C. Ott, L. Wüstefeld, N. Offen, R. A. Neher, M. Mitkovski, D. Winkler, S. Sperling, L. Fries, S. Goebbels, I. C. Vreja, N. Hagemeyer, M. Dittrich, M. F. Rossetti, K. Kröhnert, K. Hannke, S. Boretius, A. Zeug, C. Höschen, T. Dandekar, E. Dere, E. Neher, S. O. Rizzoli, K.-A. Nave, A.-L. Sirén, H. Ehrenreich
URN:urn:nbn:de:bvb:20-opus-186669
Document Type:Journal article
Faculties:Medizinische Fakultät / Neurochirurgische Klinik und Poliklinik
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):Molecular Psychiatry
Year of Completion:2016
Volume:21
Issue:12
Pagenumber:1752-1767
Source:Molecular Psychiatry (2016) 21:12, 1752-1767. https://doi.org/10.1038/mp.2015.212
DOI:https://doi.org/10.1038/mp.2015.212
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:brain-injury; cognitive functions; memory; mice; mouse-brain; nervous-sytem; neural stem-cells; progenitors; pyramidal neurons; recombinat-human-erythropoietin
Release Date:2020/05/27
Licence (German):License LogoCC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International