Effects of treadmill exercise on cognitive functions and anxiety-related behaviors in ovariectomized diabetic rats

Diabetes mellitus and ovarian hormone deficiency are associated with mood and cognition disorders. We aimed to study the possible beneficial effects of treadmill exercise on cognitive impairments and anxiety-related behaviors in ovariectomized diabetic rats. Fourteen days after bilateral ovariectomy or sham operation, adult female Wistar rats (n = 7 per group) received an intraperitoneal injection of streptozotocin (60 mg/kg) for induction of diabetes mellitus or citrate buffer. After 14 days, the animals were subjected to treadmill running or placed on the stationary treadmill for 4 weeks (5 days/week). The animals were then subjected to Morris water maze (MWM), elevated plus maze (EPM), and open field test to determine spatial learning and memory, anxiety-related behaviors, and locomotor activity, respectively. Spatial learning decreased in diabetic and ovariectomized + diabetic (Ovx + Dia) groups. Decreased spatial memory and increased anxiety levels were observed in the Ovx, Dia, and Ovx + Dia groups. Animals in the Ovx + Dia group showed reduced locomotor activity. Treadmill exercise improved spatial memory and anxiety levels in the Ovx and Dia groups, while had no significant effect on spatial learning and memory, anxiety levels, and locomotor activity in the Ovx + Dia group. Collectively, our results showed that physical exercise has beneficial effects on anxiety-related behaviors and spatial memory, but not of learning, in the ovariectomized and diabetic animals. Co-existence of ovariectomy and diabetes exacerbates anxiety-related behaviors, but not cognitive functions, compared to diabetes or ovariectomy alone; these complications could not be improved by exercise.