Thyroid hormones (TH) play a crucial role in new neuron production and maturation during brain development. In the present study, we investigated the effect of treadmill exercise on short-term memory and neurogenesis in the hippocampus with methimazol ... 
          
          
            Thyroid hormones (TH) play a crucial role in new neuron production and maturation during brain development. In the present study, we investigated the effect of treadmill exercise on short-term memory and neurogenesis in the hippocampus with methimazole (MMI)-induced hypothyroid rats. In this study, we investigated the effects of postnatal treadmill exercise on the memory capability, spatial learning ability, and depressive state, on the 5-hydroxytryptamine (5-HT, serotonin) synthesis, 5-HT1A, and tryptophan hydroxylase (TPH) expression in the dorsal raphe nuclei, and on the apoptosis (caspase-3, DNA fragmentation, Bax, Bcl-2) and neurogenesis (5-bromo-2'-deoxyuridine, BrdU; doublecortin, DCX; polysialylated neuronal cell adhesion molecule, PSA-NCAM; calbindin, brain-derived neurotrophic factor, BDNF; TrkB) in the hippocampal dentate gyrus of rat pups following hypothyroidism. On the day of perinatal 14, the pregnant rats were divided into two groups (n = 5 in each group): the maternal control group (n = 5) and the maternal MMI-treated group. For the rats in the maternal MMI-treated group, MMI was added to the drinking water (0.02% wt/vol), replaced daily with fresh MMI solution from the day of perinatal 14 to postnatal 49. After delivery, rat pups were divided into 8 groups: control group (n=10, control and low intensity exercise group (n=10), control and moderate intensity exercise group (n=10), control and high intensity-exercise group (n=10), MMI injection group (n=10), MMI-injection and low-intensity exercise group (n=10), MMI-injection and moderate-intensity exercise group (n=10), MMI-injection and high-intensity exercise group (n=10). In order to induce hypthyroid rat, pregnant rats were treated with 0.02% MMI in drinking water beginning at the 14 day of pregnancy and continuing until postnatal day 49. The rat in the exercise groups were forced to run on a treadmill for 30 min once a day from postnatal day 28 to postnatal day 56 (4 weeks). The low-intensity exercise consisted of running at a speed of 2 m/min for the first 5 min, 3 m/min for the next 5 min, and 4 m/min for the last 20 min. The moderate-intensity exercise consisted of running at a speed of 5 m/min for the first 5 min, 8 m/min for the next 5 min, and 11 m/min for the last 20 min. The high-intensity exercise consisted of running at a speed of 8 m/min for the first 5 min, 16 m/min for the next 5 min, and 22 m/min for the last 20 min with a 0° inclination. The rat pups in the hypothyroidism group showed depressive state with deceased memory capability and learning ability. Postnatal treadmill exercise increased memory capability and learning ability and alleviated depressive state of the rat pups in the hypothyroidism group. The neurogenesis factors (BrdU, DCX, calbindin), and BDNF, TrkB expression in the hippocampal dentate gyrus was significantly decreased, and PSA-NCAM expression increased  in the hypothyroid rat pups, and postnatal treadmill exercise increased the neurogenesis factors and BDNF, TrkB expression, and decreased PSA-NCAM expression. In contrast, apoptotic neuronal cell death in the hippocampal dentate gyrus was significantly increased in the hypothyroid rat pups, and postnatal treadmill exercise suppressed the hypothyroidism-induced apoptosis. The 5-HT synthesis, TPH, 5-HT1A expressions in the dorsal raphe nuclei were significantly decreased in the hypothyroid rat pups, and postnatal treadmill exercise increased 5-HT synthesis, the TPH expression, 5-HT1A, whereas there was no significant difference among intensities. The present results demonstrated that postnatal treadmill exercise alleviated hypothyroidism-induced depression with decrease of memory capability and learning ability, by suppressing apoptotic neuronal cell death and by enhancing neurogenesis and serotonergic pathway.