title: Impairment of spatial learning and memory in transgenic mice overexpressing human fibroblast growth factor-23.
abstract: Fibroblast growth factor-23 (FGF-23) is a potent circulating phosphaturic factor associated with renal phosphate wasting. Effects of FGF-23 on skeleton, phosphate homeostasis, and cardiovascular system have been investigated; however, the effect of FGF-23 on the central nervous system (CNS) is unknown. To assess whether FGF-23 influences the function and structure of the CNS and whether the effect of FGF-23 on the CNS is mediated by FGF receptors directly or by hypophosphatemia indirectly, FGF-23 transgenic mice and their wild-type littermates were fed a normal diet or a high-phosphate diet containing a normal diet plus 1.25% phosphate in drinking water from weaning for 5weeks and the phenotypes of the CNS were compared between FGF-23 transgenic mice and their wild-type littermates on the same diet. At the end of this time period, transgenic animals on the normal diet showed impaired spatial learning and memory. Furthermore, these mice exhibited the impairment of long-term potentiation in hippocampal CA1 region, and the reduction of hippocampal adenosine-triphosphate content and of choline acetyltransferase-positive neurons in basal forebrain, possibly as pathogenetic factors contributing to the cognitive deficit. The central nervous phenotypes of transgenic mice were rescued following improved hypophosphatemia by the high-phosphate diet intake. This study demonstrates that FGF-23 overexpression can result in abnormalities in the CNS mediated by the secondary severe hypophosphatemia.
authors.affiliation: Department of Toxicology, School of Public Health, Southeast University, Nanjing 210009, PR China.
authors.forename: Peidang
authors.initials: P
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Xiuying
authors.initials: X
authors.lastname: Bai
authors.forename: Andrew
authors.initials: A
authors.lastname: Karaplis
authors.forename: Dengshun
authors.initials: D
authors.lastname: Miao
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D017674:Hypophosphatemia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000235:genetics*; D018782:Maze Learning / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism
chemical_list: C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000255:Adenosine Triphosphate; D002795:Choline O-Acetyltransferase