TY - JOUR
T1 - FGF-23 deficiency impairs hippocampal-Dependent cognitive function
AU - Laszczyk, Ann M.
AU - Nettles, Dailey
AU - Pollock, Tate A.
AU - Fox, Stephanie
AU - Garcia, Melissa L.
AU - Wang, Jing
AU - Darryl Quarles, L.
AU - King, Gwendalyn D.
N1 - Funding Information:
D.N., T.A.P., S.F., L.D.Q., and G.D.K. wrote the paper. This work was supported in part by National Institutes of Health Grants R00AG034989 and R56AG052936 (to G.D.K.) and T32NS061788 (to A.M.L.). Correspondence should be addressed to Gwendalyn D. King at gdking@uab.edu. https://doi.org/10.1523/ENEURO.0469-18.2019 Copyright © 2019 Laszczyk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Publisher Copyright:
© 2019 Laszczyk et al.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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.
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.
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U2 - 10.1523/ENEURO.0469-18.2019
DO - 10.1523/ENEURO.0469-18.2019
M3 - Article
C2 - 30911673
AN - SCOPUS:85063712138
VL - 6
JO - eNeuro
JF - eNeuro
SN - 2373-2822
IS - 2
M1 - e0469-18.2019
ER -