title: The hematopoietic cytokine granulocyte-macrophage colony stimulating factor is important for cognitive functions.
abstract: We recently reported expression of hematopoietic growth factor GM-CSF and its receptor (GM-CSFR) in CNS neurons. Here we evaluated this system in learning and memory formation using GM-CSF deficient mice. In complementation, GM-CSF signalling was manipulated specifically in adult murine hippocampus by adeno-associated virus (AAV)-mediated GM-CSFR alpha overexpression or knock-down. GM-CSF ablation caused various hippocampus and amygdala-dependent deficits in spatial and fear memory while rendering intact basic parameters like motor function, inherent anxiety, and pain threshold levels. Corroborating these data, spatial memory of AAV-injected mice was positively correlated with GM-CSFRα expression levels. Hippocampal neurons of knock-out mice showed markedly pruned dendritic trees, reduced spine densities, and lower percentages of mature spines. Despite such morphological alterations, long-term potentiation (LTP) was unimpaired in the knock-out hippocampus. Collectively, these results suggest that GM-CSF signalling plays a major role in structural plasticity relevant to learning and memory.
authors.affiliation: SYGNIS Bioscience, Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Krieger
authors.forename: Martin
authors.initials: M
authors.lastname: Both
authors.forename: Simon A
authors.initials: SA
authors.lastname: Kranig
authors.forename: Claudia
authors.initials: C
authors.lastname: Pitzer
authors.forename: Matthias
authors.initials: M
authors.lastname: Klugmann
authors.forename: Gerhard
authors.initials: G
authors.lastname: Vogt
authors.forename: Andreas
authors.initials: A
authors.lastname: Draguhn
authors.forename: Armin
authors.initials: A
authors.lastname: Schneider
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism; D001522:Behavior, Animal; D003071:Cognition / Q000502:physiology*; D000229:Dependovirus / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D017774:Long-Term Potentiation; D008297:Male; D018782:Maze Learning; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D009048:Motor Skills; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor