title: Improvement of cognitive impairment in female type 2 diabetes mellitus mice by spironolactone.
abstract: Patients with type 2 diabetes mellitus (T2DM) exhibit more severe cognitive decline in females compared with males; however, the preventive approach to this gender-specific cognitive decline is still an enigma. Spironolactone is a potassium-sparing diuretic that also acts as an androgen receptor antagonist. Here, we investigated whether spironolactone attenuates cognitive impairment observed in female T2DM mice. Adult wild-type (WT) mice and an obese T2DM model, KKAy mice, were employed in this study. Cognitive function was evaluated by the shuttle avoidance test and Morris water maze test. Administration of spironolactone (50 mg/kg per day in chow) had no significant effect on blood pressure, glucose tolerance or insulin resistance. In WT mice, no significant sex difference in cognitive function was observed; however, treatment with spironolactone improved spatial memory in the water maze, especially in female WT mice. Administration of spironolactone markedly improved the cognitive decline in female KKAy mice up to the level in male KKAy mice. Spironolactone treatment also improved cognitive function in ovariectomized-KKAy mice, but failed to improve it in those with administration of estradiol (200 µg/kg per day). In diabetic mice, spironolactone improved impaired cognitive function observed in female mice, suggesting that spironolactone may prevent cognitive impairment associated with diabetes in females clinically.
authors: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Tohon, Ehime, Japan.
authors: Akiko
authors: A
authors: Sakata
authors: Masaki
authors: M
authors: Mogi
authors: Jun
authors: J
authors: Iwanami
authors: Kana
authors: K
authors: Tsukuda
authors: Li-Juan
authors: LJ
authors: Min
authors: Fei
authors: F
authors: Jing
authors: Kousei
authors: K
authors: Ohshima
authors: Masaharu
authors: M
authors: Ito
authors: Masatsugu
authors: M
authors: Horiuchi
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003072:Cognition Disorders / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D004573:Electrolytes / Q000097:blood; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006728:Hormones / Q000097:blood; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D013148:Spironolactone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013599:Systole / Q000187:drug effects
chemical_list: D004573:Electrolytes; D006728:Hormones; D013148:Spironolactone; D004958:Estradiol