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Functional hypoxia drives neuroplasticity and neurogenesis via brain erythropoietin

MPS-Authors
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Wakhloo,  D.
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons270999

Scharkowski,  F.
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons270426

Curto,  Y.
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons270424

Butt,  U. J.
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons222745

Bansal,  V.
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

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Steixner-Kumar,  A. A.
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182120

Wüstefeld,  L.
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons214271

Arinrad,  S.
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons271002

Zillmann,  M. R.
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons203088

Seelbach,  A.
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182183

Hassouna,  I.
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons271004

Schneider,  K.
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182481

Werner,  H. B.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182487

Wojcik,  S. M.
Molecular neurobiology, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182320

Nave,  Klaus Armin
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182138

Ehrenreich,  H.
Clinical neuroscience, Max Planck Institute of Experimental Medicine, Max Planck Society;

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Citation

Wakhloo, D., Scharkowski, F., Curto, Y., Butt, U. J., Bansal, V., Steixner-Kumar, A. A., et al. (2020). Functional hypoxia drives neuroplasticity and neurogenesis via brain erythropoietin. Nature Communications, 11: 1313. doi:10.1038/s41467-020-15041-1.


Cite as: http://hdl.handle.net/21.11116/0000-0007-4970-9
Abstract
Erythropoietin (EPO), named after its role in hematopoiesis, is also expressed in mammalian brain. In clinical settings, recombinant EPO treatment has revealed a remarkable improvement of cognition, but underlying mechanisms have remained obscure. Here, we show with a novel line of reporter mice that cognitive challenge induces local/endogenous hypoxia in hippocampal pyramidal neurons, hence enhancing expression of EPO and EPO receptor (EPOR). High-dose EPO administration, amplifying auto/paracrine EPO/EPOR signaling, prompts the emergence of new CA1 neurons and enhanced dendritic spine densities. Single-cell sequencing reveals rapid increase in newly differentiating neurons. Importantly, improved performance on complex running wheels after EPO is imitated by exposure to mild exogenous/inspiratory hypoxia. All these effects depend on neuronal expression of the Epor gene. This suggests a model of neuroplasticity in form of a fundamental regulatory circle, in which neuronal networks—challenged by cognitive tasks—drift into transient hypoxia, thereby triggering neuronal EPO/EPOR expression.