Expression of constitutively active erythropoietin receptor in cortical neurons boosts higher cognitive functions in mice

Derya Sargin, Ahmed El-Kordi, Amit Agarwal, Michael Muller, Sonja M Wojcik, Imam Hassouna, Swetlana Sperling, Klaus-Armin Nave and Hannelore Ehrenreich

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

Abstract (provisional)

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.
Source: BMC Biology [Open Access Paper]
http://www.biomedcentral.com/1741-7007/9/27/abstract
Posted by
Robert Karl Stonjek