Organoselenium Improves Memory Decline in Mice: Involvement of Acetylcholinesterase Activity

The present study was designed to investigate the possible neuroprotective effect of p,p'-methoxyl-diphenyl diselenide [(MeOPhSe)(2)] in a model of sporadic dementia of Alzheimer's type (SDAT) induced by intracerebroventricular (i.c.v.) injection of streptozotocin (STZ) in mice. Mice were divided into four groups: (I) control, (II) (MeOPhSe)(2), (III) STZ, and (IV) (MeOPhSe)(2)+STZ. Mice were exposed to (MeOPhSe)(2) (25mg/kg, by gavage) and STZ (2mul of 2.5mg/ml solution; i.c.v.) or vehicles. 48 after that the exposure was repeated. Learning and memory were assessed with the step-down-type passive-avoidance (SDPA) and Morris water-maze (MWM) tests at the days 5-6 and 6-9, respectively. At the end of the experimental protocol animals were euthanized and cerebral cortex was removed for acetylcholinesterase (AChE) activity assay. Our results confirmed that i.c.v. STZ caused learning and memory deficits in mice, which were verified using the MWM and SDPA tasks. Furthermore, this study showed that AChE activity was increased in mice that received i.c.v. STZ. The most important findings of the present study are that (MeOPhSe)(2) was able to reverse the learning and memory impairments induced by STZ, and to protect against the increase in AChE activity. All these findings support the neuroprotective role of (MeOPhSe)(2) in a mice model of SDAT induced by i.c.v. STZ.