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          Institute: MPI für Entwicklungsbiologie     Collection: Abteilungsunabhängige Arbeitsgruppen     Display Documents



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ID: 733160.0, MPI für Entwicklungsbiologie / Abteilungsunabhängige Arbeitsgruppen
Revisiting adult neurogenesis and the role of erythropoietin for neuronal and oligodendroglial differentiation in the hippocampus
Authors:Hassouna, I.; Ott, C.; Wustefeld, L.; Offen, N.; Neher, R. A.; Mitkovski, M.; Winkler, D.; Sperling, S.; Fries, L.; Goebbels, S.; Vreja, I. C.; Hagemeyer, N.; Dittrich, M.; Rossetti, M. F.; Krohnert, K.; Hannke, K.; Boretius, S.; Zeug, A.; Hoschen, C.; Dandekar, T.; Dere, E.; Neher, E.; Rizzoli, S. O.; Nave, K. A.; Siren, A. L.; Ehrenreich, H.
Date of Publication (YYYY-MM-DD):2016-12
Title of Journal:Mol Psychiatry
Volume:21
Issue / Number:12
Start Page:1752
End Page:1767
Review Status:Internal review
Audience:Not Specified
Abstract / Description: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 ~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 15N-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 15N-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.
External Publication Status:published
Document Type:Article
Affiliations:MPI für Entwicklungsbiologie/Abteilungsunabhängige Arbeitsgruppen/Arbeitsgruppe Neher
MPI für biophysikalische Chemie/Abt. Erwin Neher / 140
External Affiliations:On leave of absence from Physiology Unit, Zoology Department, Faculty of Science, Menoufia University, Al Minufya, Egypt. Department of Neurosurgery, University of Wurzburg, Wurzburg, Germany. Evolutionary Dynamics and Biophysics, Max Planck Institute for Developmental Biology, Tubingen, Germany. Light Microscopy Facility, Max Planck Institute of Experimental Medicine, Gottingen, Germany. Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Gottingen, Germany. Department of Neuro- and Sensory Physiology, University Medical Center Gottingen, Germany. International Max Planck Research School Molecular Biology, Gottingen, Germany. Department of Bioinformatics, Biocenter, University of Wurzburg, Wurzburg, Germany. Department of Diagnostic Radiology, Christian-Albrechts-Universitat, Kiel, Germany. Cellular Neurophysiology, Hannover Medical School, Hannover, Germany. Department of Ecology and Ecosystem Management, Lehrstuhl fur Bodenkunde, Technische Universitat Munchen, Freising-Weihenstephan, Germany. Department of Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, Gottingen, Germany. DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany.
Identifiers:ISSN:1476-5578 (Electronic) 1359-4184 (Linking) %R 10.1... [ID No:1]
URL:https://www.ncbi.nlm.nih.gov/pubmed/26809838 [ID No:2]
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