1,25(OH)2D3 dependent overt hyperactivity phenotype in klotho-hypomorphic mice.
Klotho, a protein mainly expressed in kidney and cerebral choroid plexus, is a powerful regulator of 1,25(OH)2D3 formation. Klotho-deficient mice (kl/kl) suffer from excessive plasma 1,25(OH)2D3-, Ca(2+)- and phosphate-concentrations, leading to severe soft tissue calcification and accelerated aging. NH4Cl treatment prevents tissue calcification and premature ageing without affecting 1,25(OH)2D3-formation. The present study explored the impact of excessive 1,25(OH)2D3 formation in NH4Cl-treated kl/kl-mice on behavior. To this end kl/kl-mice and wild-type mice were treated with NH4Cl and either control diet or vitamin D deficient diet (LVD). As a result, plasma 1,25(OH)2D3-, Ca(2+)- and phosphate-concentrations were significantly higher in untreated and in NH4Cl-treated kl/kl-mice than in wild-type mice, a difference abrogated by LVD. In each, open field, dark-light box, and O-maze NH4Cl-treated kl/kl-mice showed significantly higher exploratory behavior than untreated wild-type mice, a difference abrogated by LVD. The time of floating in the forced swimming test was significantly shorter in NH4Cl treated kl/kl-mice compared to untreated wild-type mice and to kl/kl-mice on LVD. In wild-type animals, NH4Cl treatment did not significantly alter 1,25(OH)2D3, calcium and phosphate concentrations or exploratory behavior. In conclusion, the excessive 1,25(OH)2D3 formation in klotho-hypomorphic mice has a profound effect on murine behavior.
Department of Physiology, Cardiology &Vascular Medicine, University of Tübingen, Gmelinstr. 5, 72076 Tübingen, Germany.
Christina B
CB
Leibrock
Department of Physiology, Cardiology &Vascular Medicine, University of Tübingen, Gmelinstr. 5, 72076 Tübingen, Germany.
Jakob
J
Voelkl
Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
Makoto
M
Kuro-O
Department of Physiology, Cardiology &Vascular Medicine, University of Tübingen, Gmelinstr. 5, 72076 Tübingen, Germany.
Florian
F
Lang
Department of Psychiatry, University of Basel, Wilhelm Klein-Strasse 27, CH-4012 Basel, Switzerland.
Undine E
UE
Lang
D000643:Ammonium Chloride / Q000008:administration & dosage; D000818:Animals; D002118:Calcium / Q000097:blood; D004100:Dihydroxycholecalciferols / Q000097:blood / Q000378:metabolism*; D005106:Exploratory Behavior; D005966:Glucuronidase / Q000172:deficiency*; D006948:Hyperkinesis; D000090265:Klotho Proteins; D051379:Mice; D010710:Phosphates / Q000097:blood; D011595:Psychomotor Agitation
D004100:Dihydroxycholecalciferols; D010710:Phosphates; D000643:Ammonium Chloride; C023850:1 alpha,24-dihydroxyvitamin D3; D005966:Glucuronidase; D000090265:Klotho Proteins; D002118:Calcium