In the present study, we investigated the effects of type 2 diabetes and treadmill exercise in chronic diabetic stages on neuroblast differentiation using doublecortin (DCX) in the subgranular zone of the dentate gyrus (SZDG) in Zucker diabetic fatty (ZDF) rats. Four-, 12-, 20- and 30-week-old Zucker lean control (ZLC) and ZDF rats were used to elucidate age-dependent changes of DCX-immunoreactive neuroblasts. DCX-immunoreactive neuroblasts were significantly decreased with age in the SZDG. This reduction was prominent in the age-matched ZDF rats compared to that in the ZLC rats. To investigate the effects of treadmill exercise, ZLC and ZDF rats at 23 weeks of age were put on the treadmill with or without running for 1 h/day/5 consecutive days at 12-16 m/min for 7 weeks. Treadmill exercise significantly increased the tertiary dendrites of DCX-immunoreactive neuroblasts in both ZLC and ZDF rats. In addition, exercise significantly increased the number of DCX-immunoreactive neuroblasts in the ZLC rats, but not in the ZDF rats. These results suggest that diabetes significantly decreases neuroblast differentiation and treadmill exercise in chronic diabetic animals has limitation to increase neuroblast differentiation although it increases neural plasticity.
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