Effects of treadmill exercise on cyclooxygenase-2 in the hippocampus in type 2 diabetic rats: Correlation with the neuroblasts

Cyclooxygenase (COX) is a rate-limiting enzyme in synthesis of prostaglandins from arachidonic acid. In this study, we observed the effects of a physical exercise on COX-2 immunoreactivity in the hippocampus using immunohistochemistry in rats. In addition, we examined effects of administration of a COX-2 inhibitor, celecoxib, on neuroblast differentiation. At 6weeks of age, Zucker lean control (ZLC) and Zucker diabetic fatty (ZDF) rats were put on a treadmill with or without running for 1h/session/day for 5weeks. The running speed was gradually increased from 16 to 22m/min with 2m/min per 2weeks. In the ZLC and ZDF rats, COX-2 immunoreaction was detected in the granule cell layer of the dentate gyrus and in the stratum pyramidale of the CA2/3 region; COX-2 immunoreaction in the CA1 region was hardly detected. In the exercised-ZLC and ZDF rats, COX-2 immunoreactivity was significantly increased compared to that in the ZLC and ZDF rats, showing that COX-2 immunoreactivity in the exercised-ZDF rats was slightly low than that in the exercised-ZDF rats. In addition, weak COX-2 immunoreactivity was shown in the CA1 region by exercise. On the other hand, the repeated oral administration of celecoxib to 4-week-old ZDF rats significantly decreased the neuroblasts in the subgranular zone of the dentate gyrus. These results suggest that COX-2 may be associated with the increase of synaptic plasticity or contacts in the hippocampus.