It is known that
selenium (Se) might play different roles in the progression of
Alzheimer's disease (AD), but there is a lack of evidence that proves whether supplementation with Se is beneficial or not for the treatment of AD. Thus, the aim of the current study was to investigate the
therapeutic effect of
p,p'-methoxyl-diphenyl diselenide [(
MeOPhSe)(2)], an organoselenium compound, against
streptozotocin (STZ)-induced sporadic
dementia of Alzheimer's type (SDAT) in rats. Male Wistar rats received STZ twice daily (1.0 mg/8 μl; 4 μl/ventricle) for 21 days. After 21 days of STZ injection, regular-diet-fed rats were supplemented with 10 ppm of (
MeOPhSe)(2) during 30 days. At the end of this period, the rats were challenged in the Morris water maze and step-down passive avoidance tasks. The activity of
acetylcholinesterase (AChE), deficit in cerebral energy metabolism (measurement of
adenosine 5-
triphosphate and
adenosine 5-
diphosphate levels), and oxidative and nitrosative stress were determined in the cortex and hippocampus of rats. The results demonstrated that (
MeOPhSe)(2) dietary supplementation reverted STZ-induced memory impairment of rats in both cognitive tasks. The findings also indicated that (
MeOPhSe)(2) dietary supplementation reverted oxidative stress in the STZ group (decreased reactive species and
tyrosine nitration levels and enhanced nonprotein
thiol levels). Moreover, (
MeOPhSe)(2) dietary supplementation normalized AChE activity, which was enhanced by STZ injection, but did not revert the deficit in cerebral energy metabolism caused by STZ. The results of the present study indicated the
therapeutic effect of the (MeOPhSe)(2)-supplemented diet in a rat model of SDAT.