Functional hypoxia drives neuroplasticity and neurogenesis via brain 
erythropoietin

Wakhloo, D.; Scharkowski, F.; Curto, Y.; Butt, U. J.; Bansal, V.; Steixner-Kumar, A. A.; Wüstefeld, L.; Rajput, A.; Arinrad, S.; Zillmann, M. R.; Seelbach, A.; Hassouna, I.; Schneider, K.; Qadir Ibrahim, A.; Werner, Hauke B.; Werner, H. B.; Martens, H.; Miskowiak, K.; Wojcik, Sonja M.; Wojcik, S. M.; Bonn, S.; Nacher, J.; Nave, Klaus Armin; Ehrenreich, H.

doi:10.1038/s41467-020-15041-1

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Functional hypoxia drives neuroplasticity and neurogenesis via brain erythropoietin

MPS-Authors

/persons/resource/persons215467

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;

/persons/resource/persons268847

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;

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

3260529.pdf
(Publisher version), 5MB

Supplementary Material (public)

There is no public supplementary material available

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: https://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.