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Open Access Research article

Expression of constitutively active erythropoietin receptor in pyramidal neurons of cortex and hippocampus boosts higher cognitive functions in mice

Derya Sargin1, Ahmed El-Kordi12, Amit Agarwal3, Michael Müller24, Sonja M Wojcik5, Imam Hassouna1, Swetlana Sperling1, Klaus-Armin Nave23* and Hannelore Ehrenreich12*

Author Affiliations

1 Division of Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str.3, 37075 Göttingen, Germany

2 DFG Research Center for Molecular Physiology of the Brain (CMPB), Humboldtallee 23, 37073 Göttingen, Germany

3 Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str.3, 37075 Göttingen, Germany

4 Department of Neuro- and Sensory Physiology, Georg-August-University, Humboldtallee 23, 37073 Göttingen, Germany

5 Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str.3, 37075 Göttingen, Germany

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BMC Biology 2011, 9:27  doi:10.1186/1741-7007-9-27

Published: 28 April 2011

Abstract

Background

Erythropoietin (EPO) and its receptor (EPOR) are expressed in the developing brain and their transcription is upregulated in adult neurons and glia upon injury or neurodegeneration. We have shown neuroprotective effects and improved cognition in patients with neuropsychiatric diseases treated with EPO. However, the critical EPO targets in brain are unknown, and separation of direct and indirect effects has remained difficult, given the role of EPO in hematopoiesis and brain oxygen supply.

Results

Here we demonstrate that mice with transgenic expression of a constitutively active EPOR isoform (cEPOR) in pyramidal neurons of cortex and hippocampus exhibit enhancement of spatial learning, cognitive flexibility, social memory, and attentional capacities, accompanied by increased impulsivity. Superior cognitive performance is associated with augmented long-term potentiation of cEPOR expressing neurons in hippocampal slices.

Conclusions

Active EPOR stimulates neuronal plasticity independent of any hematopoietic effects and in addition to its neuroprotective actions. This property of EPOR signaling should be exploited for defining novel strategies to therapeutically enhance cognitive performance in disease conditions.