Comparison of the effects of erythropoietin and its carbamylated derivative on behaviour and hippocampal neurogenesis in mice

Erythropoietin (EPO), a well known haematopoietic growth factor, possesses neuroprotective and neurotrophic effects which have been recently reported to improve cognition and to modulate emotional processing. We investigated the effects of EPO and of its non-erythropoietic carbamylated derivative (CEPO) on memory- and emotion-related behaviour in the adult mouse. Locomotor activity, memory performances (place and object recognition tasks), anxiety- (light/dark transition test) and despair-like behaviours (tail suspension test) were assessed over 6 weeks of repeated EPO or CEPO administration (40 μg/kg, twice a week). Given the potential involvement of hippocampal neurogenesis in memory, we also assessed the effects of EPO and CEPO on neurogenesis in the dentate gyrus. Both treatments improved spatial and non-spatial recognition memory and increased the number of NeuN/BrdU double-labeled cells in the dentate gyrus. These effects seem to be, at least partly, independent from an haematopoietic action since administration of CEPO leads to the similar results. Moreover, CEPO decreased, albeit modestly, despair-related behaviour and tended to decrease anxiety-like behaviour. These results suggest that CEPO is as an attractive molecule for the treatment of neuropsychiatric diseases associating memory and/or emotional disorders.