PT  - JOURNAL ARTICLE
AU  - Ann M. Laszczyk
AU  - Dailey Nettles
AU  - Tate A. Pollock
AU  - Stephanie Fox
AU  - Melissa L. Garcia
AU  - Jing Wang
AU  - L. Darryl Quarles
AU  - Gwendalyn D. King
TI  - FGF-23 Deficiency Impairs Hippocampal-Dependent Cognitive Function
AID  - 10.1523/ENEURO.0469-18.2019
DP  - 2019 Mar 01
TA  - eneuro
PG  - ENEURO.0469-18.2019
VI  - 6
IP  - 2
4099  - http://www.eneuro.org/content/6/2/ENEURO.0469-18.2019.short
4100  - http://www.eneuro.org/content/6/2/ENEURO.0469-18.2019.full
SO  - eNeuro2019 Mar 01; 6
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.