TY - JOUR
T1 - Expression of constitutively active erythropoietin receptor in pyramidal neurons of cortex and hippocampus boosts higher cognitive functions in mice
AU - Sargin, Derya
AU - El-Kordi, Ahmed
AU - Agarwal, Amit
AU - Müller, Michael
AU - Wojcik, Sonja M.
AU - Hassouna, Imam
AU - Sperling, Swetlana
AU - Nave, Klaus Armin
AU - Ehrenreich, Hannelore
N1 - Funding Information:
This study was supported by the Max Planck Society and the DFG-Research Center for Molecular Physiology of the Brain (CMBP). The authors thank Prof. Harvey F. Lodish, Cambridge, MA, for kindly providing the cEPOR construct. Belinda Hildebrandt and Anja Ronnenberg are acknowledged for their excellent technical help.
PY - 2011/4/28
Y1 - 2011/4/28
N2 - 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.
AB - 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.
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U2 - 10.1186/1741-7007-9-27
DO - 10.1186/1741-7007-9-27
M3 - Article
C2 - 21527022
AN - SCOPUS:79955133405
SN - 1741-7007
VL - 9
JO - BMC Biology
JF - BMC Biology
M1 - 27
ER -