PMID- 21729993
OWN - NLM
STAT- MEDLINE
DCOM- 20120627
LR  - 20131121
IS  - 1752-8976 (Electronic)
IS  - 1470-3203 (Linking)
VI  - 13
IP  - 1
DP  - 2012 Mar
TI  - Improvement of cognitive impairment in female type 2 diabetes mellitus mice by 
      spironolactone.
PG  - 84-90
LID - 10.1177/1470320311412810 [doi]
AB  - 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 microg/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.
FAU - Sakata, Akiko
AU  - Sakata A
AD  - Department of Molecular Cardiovascular Biology and Pharmacology, Ehime 
      University, Graduate School of Medicine, Tohon, Ehime, Japan.
FAU - Mogi, Masaki
AU  - Mogi M
FAU - Iwanami, Jun
AU  - Iwanami J
FAU - Tsukuda, Kana
AU  - Tsukuda K
FAU - Min, Li-Juan
AU  - Min LJ
FAU - Jing, Fei
AU  - Jing F
FAU - Ohshima, Kousei
AU  - Ohshima K
FAU - Ito, Masaharu
AU  - Ito M
FAU - Horiuchi, Masatsugu
AU  - Horiuchi M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110705
PL  - England
TA  - J Renin Angiotensin Aldosterone Syst
JT  - Journal of the renin-angiotensin-aldosterone system : JRAAS
JID - 100971636
RN  - 0 (Electrolytes)
RN  - 0 (Hormones)
RN  - 27O7W4T232 (Spironolactone)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Body Weight/drug effects
MH  - Cognition Disorders/blood/*complications/*drug therapy/physiopathology
MH  - Diabetes Mellitus, Type 2/blood/*complications/*drug therapy/physiopathology
MH  - Electrolytes/blood
MH  - Estradiol/administration & dosage/pharmacology
MH  - Female
MH  - Hormones/blood
MH  - Male
MH  - Memory/drug effects
MH  - Mice
MH  - Organ Size/drug effects
MH  - Ovariectomy
MH  - Spironolactone/administration & dosage/pharmacology/*therapeutic use
MH  - Systole/drug effects
EDAT- 2011/07/07 06:00
MHDA- 2012/06/28 06:00
CRDT- 2011/07/07 06:00
PHST- 2011/07/07 06:00 [entrez]
PHST- 2011/07/07 06:00 [pubmed]
PHST- 2012/06/28 06:00 [medline]
AID - 1470320311412810 [pii]
AID - 10.1177/1470320311412810 [doi]
PST - ppublish
SO  - J Renin Angiotensin Aldosterone Syst. 2012 Mar;13(1):84-90. doi: 
      10.1177/1470320311412810. Epub 2011 Jul 5.