title: Reduced CXCL12/CXCR4 results in impaired learning and is downregulated in a mouse model of Alzheimer disease.
abstract: Alzheimer disease (AD) is characterized by the presence of plaques and tangles in parallel with progressive cognitive decline. The underlying cause of the cognitive decline is unknown. The purpose of this study was to identify factors that could affect learning and memory using the Tg2576 mouse model of AD. Un-biased GeneChip analysis at the time-point coinciding with the onset of behavioral deficits but prior to plaque deposition revealed that Tg2576 show altered gene expression for a number of molecules including the chemokine CXCL12. We show that this chemokine's mRNA, protein and receptor are downregulated in this mouse model coinciding with cognitive deficits. Furthermore, we demonstrate that CXCL12 levels are decreased in AD patients as compared to controls. To determine if CXCL12 might be related to impaired learning and memory, we chronically treated young non-transgenic mice with an antagonist to the CXCL12 receptor to simulate the reduction seen in transgenic animals. Treated animals showed selectively impaired learning and memory suggesting a potential role for this chemokine in cognitive functioning.
authors.affiliation: Institute for Brain Aging and Dementia, University of California, 1113 Gillespie Neuroscience Research Facility, Irvine, CA 92697-4540, USA. aparachi@uci.edu
authors.forename: A
authors.initials: A
authors.lastname: Parachikova
authors.forename: C W
authors.initials: CW
authors.lastname: Cotman
mesh_terms: D000375:Aging / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001596:Benzylamines; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000033:anatomy & histology / Q000276:immunology* / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000235:genetics / Q000276:immunology*; D000080027:Cyclams; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D004660:Encephalitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006624:Hippocampus / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007859:Learning Disabilities / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D009435:Synaptic Transmission / Q000235:genetics / Q000276:immunology
chemical_list: D016229:Amyloid beta-Peptides; D001596:Benzylamines; D015415:Biomarkers; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D000080027:Cyclams; D006571:Heterocyclic Compounds; D012333:RNA, Messenger; D019718:Receptors, CXCR4; C088327:plerixafor