Background: Levosimendan is a calcium sensitizer and phosphodiesterase inhibitor that has
potent antioxidant and anti-inflammatory activities.
Objectives: The aim of the current study is to investigate the potential protective effect of levosimendan
on learning and memory impairment induced by diabetes.
Methods: Adult Wister rats were randomly divided into four groups (n=15 rats/group): control,
levosimendan, streptozotocin (STZ) induced diabetes, and levosimendan-STZ diabetes. Upon confirmation
of the success of the STZ diabetic model, intraperitoneal levosimendan (100µg/kg/week) was administrated
to the assigned groups for 4 weeks. Then, the radial arm water maze was used to evaluate
spatial learning and memory. Oxidative stress biomarkers and brain-derived neurotrophic factor were
evaluated in hippocampal tissues.
Results: The results showed that Diabetes Mellitus (DM) impaired both short- and long- term memory
(P<0.01), while levosimendan protected the animals from memory impairment. In addition, levosimendan
prevented DM-induced reduction in the hippocampal levels of superoxide dismutase and glutathione
peroxidase (P<0.05). Moreover, the administration of levosimendan prevented DM-induced increases in
hippocampal thiobarbituric acid reactive substances level (P<0.05). Furthermore, levosimendan restored
the ratio of reduced/oxidized glutathione (GSH/GSSG) in DM rats to that observed in the control group
Conclusions: In summary, DM induced learning and memory impairment, and treatment with
levosimendan impeded this impairment probably through preventing alterations in the antioxidant system
in the hippocampus.