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.
Highlights
Granulocyte-colony stimulating factor (G-CSF), a hematopoietic growth factor known for its prominent role in proliferation and differentiation of hematopoietic cells [1,2], is one of a surprising variety of peripheral circulating peptides that have the ability to alter CNS functions and structure
Radial maze spatial memory task We examined the effects of G-CSF treatment on reference and working memory during spatial learning
Our data show that treatment with the hematopoietic factor GCSF combined with cognitive training improves long-term spatial memory and promotes the survival of newborn hippocampal neurons
Summary
Granulocyte-colony stimulating factor (G-CSF), a hematopoietic growth factor known for its prominent role in proliferation and differentiation of hematopoietic cells [1,2], is one of a surprising variety of peripheral circulating peptides that have the ability to alter CNS functions and structure Several of these peptides, including G-CSF, have specific receptors in the brain and, most importantly, are even produced in the brain [3]. Recent studies showed that peripheral peptides like erythropoietin [4], Insulinlike growth factor 1 [5,6], Glucagon-like peptide-1 [7] and ghrelin [8] exert action in the CNS Some of these factors have been shown to induce neuroplasticity and in the hippocampus, changes in neuronal complexity, neurogenesis and LTP. CREB activation is thought to facilitate the survival of neuronal precursors and to recruit new neurons into the dentate gyrus [12]
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