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 (50mg/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.
Chae
Chang-Hun
CH
School of Sport Science, Sungkyunkwan University, Chunchun-dong, Jangan-gu, Suwon 440-746, South Korea.
Kim
Hyun-Tae
HT
D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D005080:Exercise Test; D005081:Exercise Therapy / Q000379:methods; D005690:Galactose / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008569:Memory Disorders / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D020932:Nerve Growth Factor / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005690:Galactose