title: Synergetic effects of granulocyte-colony stimulating factor and cognitive training on spatial learning and survival of newborn hippocampal neurons.
abstract: Granulocyte-Colony Stimulating Factor (G-CSF) is an endogenous hematopoietic growth factor known for its role in the proliferation and differentiation of cells of the myeloic lineage. Only recently its significance in the CNS has been uncovered. G-CSF attenuates apoptosis and controls proliferation and differentiation of neural stem cells. G-CSF activates upstream kinases of the cAMP response element binding protein (CREB), which is thought to facilitate the survival of neuronal precursors and to recruit new neurons into the dentate gyrus. CREB is also essential for spatial long-term memory formation. To assess the role and the potential of this factor on learning and memory-formation we systemically administered G-CSF in rats engaged in spatial learning in an eight-arm radial maze. G-CSF significantly improved spatial learning and increased in combination with cognitive training the survival of newborn neurons in the hippocampus as measured by bromodeoxyuridine and doublecortin immunohistochemistry. Additionally, G-CSF improved re-acquisition of spatial information after 26 days. These findings support the hypothesis that G-CSF can enhance learning and memory formation. Due to its easy applicability and its history as a well-tolerated hematological drug, the use of G-CSF opens up new neurological treatment opportunities in conditions where learning and memory-formation deficits occur.
authors.affiliation: Department of Neurology, University of Münster, Münster, Germany. kai.diederich@uni-muenster.de
authors.forename: Kai
authors.initials: K
authors.lastname: Diederich
authors.forename: Wolf-Rüdiger
authors.initials: WR
authors.lastname: Schäbitz
authors.forename: Katharina
authors.initials: K
authors.lastname: Kuhnert
authors.forename: Nina
authors.initials: N
authors.lastname: Hellström
authors.forename: Norbert
authors.initials: N
authors.lastname: Sachser
authors.forename: Armin
authors.initials: A
authors.lastname: Schneider
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Kuhn
authors.forename: Stefan
authors.initials: S
authors.lastname: Knecht
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D000089662:Doublecortin Protein; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D008024:Ligands; D008297:Male; D018782:Maze Learning; D008568:Memory; D055495:Neurogenesis; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013037:Spatial Behavior
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D008024:Ligands; D016179:Granulocyte Colony-Stimulating Factor