title: THE HEMATOPOIETIC CYTOKINE GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR IS INVOLVED IN COGNITIVE PROCESSING
creator: Krieger, Markus
subject: ddc-570
subject: 570 Life sciences
description: Granulocyte/macrophage colony stimulating factor (GM-CSF) is a growth factor originally discovered in the hematopoietic system. Recently presence of GM-CSF and its receptor (GM-CSFR) was reported on CNS neurons. Here we investigated whether this system is involved in cognition by evaluating learning and memory formation in GM-CSF deficient (GMko) mice. In a complementary approach, GM-CSF signalling was bidirectionally manipulated specifically in the adult hippocampus by adeno-associated virus (AAV) mediated GM-CSF receptor alpha (GM-CSFRalpha) overexpression or knock-down. In GMko mice, broad cognitive deficits were observed in all behavioural paradigms tested. Animals showed impairments in fear memory to conditioned cue, in spatial learning in an active place avoidance paradigm, and in spatial memory and re-learning flexibility in the Morris Water Maze. Additionally, knock-outs also showed diminished exploratory drive. The inferior cognitive performance was not due to secondary factors such as motor function, inherent anxiety, or pain threshold levels. Corroborating these data, spatial memory of AAV-injected mice in the MWM was enhanced or impaired dependent on GM-CSFR alpha overexpression or knock-down, respectively. GMko mice showed diminished overall dendritic length and branching complexity in the dentate gyrus (DG) and reductions in both dendritic spine density and the percentage of mature spines in the hippocampus. Despite these morphological alterations and the strong memory deficits, induction of long-term potentiation (LTP) was not impaired in the hippocampus of knock-out mice, providing an example for the complicated relationship of LTP and memory performance. Collectively, these results suggest that GM-CSF signalling plays a major and hitherto unrecognized role in neuronal structural plasticity relevant to learning and memory. This finding is of particular therapeutic relevance, as GM-CSF readily passes the intact blood-brain barrier.
date: 2011
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserver/12684/1/Dissertation_Krieger.pdf
identifier: DOI:10.11588/heidok.00012684
identifier: urn:nbn:de:bsz:16-opus-126840
identifier:   Krieger, Markus  (2011) THE HEMATOPOIETIC CYTOKINE GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR IS INVOLVED IN COGNITIVE PROCESSING.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/12684/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng