title: Expression of constitutively active erythropoietin receptor in pyramidal neurons of cortex and hippocampus boosts higher cognitive functions in mice.
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.
authors.affiliation: Division of Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Derya
authors.initials: D
authors.lastname: Sargin
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Kordi
authors.forename: Amit
authors.initials: A
authors.lastname: Agarwal
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
authors.forename: Sonja M
authors.initials: SM
authors.lastname: Wojcik
authors.forename: Imam
authors.initials: I
authors.lastname: Hassouna
authors.forename: Swetlana
authors.initials: S
authors.lastname: Sperling
authors.forename: Klaus-Armin
authors.initials: KA
authors.lastname: Nave
authors.forename: Hannelore
authors.initials: H
authors.lastname: Ehrenreich
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001288:Attention; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D003071:Cognition / Q000187:drug effects*; D004921:Erythropoietin / Q000378:metabolism / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007175:Impulsive Behavior; D007858:Learning; D008297:Male; D008568:Memory; D051379:Mice; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins; D012919:Social Behavior
chemical_list: D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin