RT Journal Article SR Electronic T1 FGF-23 Deficiency Impairs Hippocampal-Dependent Cognitive Function JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0469-18.2019 DO 10.1523/ENEURO.0469-18.2019 VO 6 IS 2 A1 Laszczyk, Ann M. A1 Nettles, Dailey A1 Pollock, Tate A. A1 Fox, Stephanie A1 Garcia, Melissa L. A1 Wang, Jing A1 Quarles, L. Darryl A1 King, Gwendalyn D. YR 2019 UL http://www.eneuro.org/content/6/2/ENEURO.0469-18.2019.abstract AB Fibroblast growth factor receptor (FGFR) and α-Klotho transduce FGF-23 signaling in renal tubules to maintain systemic phosphate/vitamin D homeostasis. Mice deficient for either the ligand, FGF-23, or the co-receptor, Klotho, are phenocopies with both showing rapid and premature development of multiple aging-like abnormalities. Such similarity in phenotype, suggests that FGF-23 and Klotho have co-dependent systemic functions. Recent reports revealed inverse central nervous system (CNS) effects of Klotho deficiency or Klotho overexpression on hippocampal synaptic, neurogenic, and cognitive functions. However, it is unknown whether FGF-23 deficiency effects function of the hippocampus. We report that, similar to Klotho-deficient mice, FGF-23-deficient mice develop dose-dependent, hippocampal-dependent cognitive impairment. However, FGF-23-deficient brains had no gross structural or developmental defects, no change in hippocampal synaptic plasticity, and only minor impairment to postnatal hippocampal neurogenesis. Together, these data provide evidence that FGF-23 deficiency impairs hippocampal-dependent cognition but otherwise results in a brain phenotype that is distinct from the KL-deficient mouse.