Forced, moderate-intensity treadmill exercise suppresses apoptosis by increasing the level of NGF and stimulating phosphatidylinositol 3-kinase signaling in the hippocampus of induced aging rats

While nerve growth factor (NGF) activates various signaling cascades, the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway plays a pivotal role in controlling the survival of neurons, although this activity declines during the aging process. We investigated the effect of forced moderate-intensity treadmill exercise on the level of NGF and the PI3-K/Akt signaling pathway in the hippocampus of induced aging rats. Forty-five male Sprague-Dawley rats were divided into the following three groups: (1) control group, in which aging was not induced (CON: n=15), (2) aging-control group, in which aging was induced but the rats were not subjected to exercise (ACON: n = 15), and (3) the aging-exercise group, in which aging was induced and the rats were subjected to treadmill exercise (AEX: n = 15). D-Galactose (50 mg/kg) was injected into the abdominal cavity for 8 weeks to induce aging. Rats were subjected to treadmill exercise 5 days a week for 8 weeks, and the speed of the treadmill was gradually increased. The protein levels of NGF, P-PI3-K, and P-Akt were significantly high in the AEX group (p < 0.01, p < 0.01, and p < 0.001, respectively). Tyrosine kinase A (Trk A) receptor level was significantly higher in the CON and AEX groups than in the ACON group (p < 0.01). TUNEL assay showed a significant reduction in apoptosis in the AEX group (p < 0.001). Caspase-3 activation was significantly decreased in the AEX and CON groups (p < 0.05). These results show that forced moderate-intensity treadmill exercise increases the level of NGF and activates P-PI3-K to induce P-Akt in order to suppress apoptotic cell death in the hippocampus of induced aging rats. (C) 2009 Elsevier Ltd. All rights reserved.