title: Diosgenin-induced cognitive enhancement in normal mice is mediated by 1,25D₃-MARRS.
abstract: We previously reported that diosgenin, a plant-derived steroidal sapogenin, improved memory and reduced axonal degeneration in an Alzheimer's disease mouse model. Diosgenin directly activated the membrane-associated rapid response steroid-binding receptor (1,25D₃-MARRS) in neurons. However, 1,25D₃-MARRS-mediated diosgenin signaling was only shown in vitro in the previous study. Here, we aimed to obtain in vivo evidence showing that diosgenin signaling is mediated by 1,25D₃-MARRS in the mouse brain. Diosgenin treatment in normal mice enhanced object recognition memory and spike firing and cross-correlation in the medial prefrontal cortex and hippocampal CA1. In diosgenin-treated mice, axonal density and c-Fos expression was increased in the medial prefrontal and perirhinal cortices, suggesting that neuronal network activation may be enhanced. The diosgenin-induced memory enhancement and axonal growth were completely inhibited by co-treatment with a neutralizing antibody for 1,25D₃-MARRS. Our in vivo data indicate that diosgenin is a memory-enhancing drug and that enhancement by diosgenin is mediated by 1,25D₃-MARRS-triggered axonal growth.
authors.affiliation: Division of Neuromedical Science, Department of Bioscience, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Tohda
authors.forename: Young-A
authors.initials: YA
authors.lastname: Lee
authors.forename: Yukiori
authors.initials: Y
authors.lastname: Goto
authors.forename: Ilka
authors.initials: I
authors.lastname: Nemere
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D004144:Diosgenin / Q000494:pharmacology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018697:Nootropic Agents / Q000378:metabolism* / Q000494:pharmacology*; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*
chemical_list: D018697:Nootropic Agents; D019704:Protein Disulfide-Isomerases; D004144:Diosgenin