Effects of treadmill exercise and sex hormones on learning, memory and hippocampal brain-derived neurotrophic factor levels in transient congenital hypothyroid rats

Abstract

Transient thyroid function abnormalities at birth exhibit intellectual developmental and cognitive disorders in adulthood. Given the well-known effects of physical activity and sex hormones on cognitive functions and brain-derived neurotrophic factor (BDNF), the present study examined the effects of treadmill exercise, sex hormones, and the combined treatment on learning and memory and hippocampal BDNF levels in transient congenital hypothyroid rats. To induce hypothyroidism, 6-propyl-2-thiouracil was added to the drinking water from the 6th day of gestation to the 21st postnatal day (PND). From PNDs 28 to 47, female and male pup rats received 17β-estradiol and testosterone, respectively, and about 30 min later, they were forced to run on the treadmill for 30 min once a day. On PNDs 48-55, spatial learning and memory of all rats tested in the water maze, which followed by measurement of BDNF in the hippocampus. Results showed that developmental hypothyroidism induced significant deficits in spatial learning and memory and hippocampal BDNF in both male and female rats. In both male and female hypothyroid rats, exercise and exercise plus sex hormones, but not sex hormones alone alleviated learning and memory deficits and all treatments (exercise, sex hormones, and the combined treatment) increased hippocampal BDNF. These disconnects in the effects of exercise, sex hormones and the combined treatment on behavioral and neurochemical outcomes suggest that a neurochemical mechanism other than hippocampal BDNF might contribute in the ameliorating effects of exercise on learning and memory deficits induced by developmental thyroid hormone insufficiency.