Neurochemistry international
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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. ⋯ 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.
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The neuroprotective roles of both hypothermia and ginkgolides have been well confirmed. We first examined whether hypothermia (32 or 28 degrees C) or ginkgolides have a protective effect on astrocytes against ischemia and reperfusion-induced injury. We demonstrated that ginkgolides, but not hypothermia, have a significantly time- and concentration-dependent protective role in ischemic astrocytes. ⋯ Data showed that the co-treatment induced a significant decrease, rather than an increase as we had expected, in their cellular viabilities and anti-apoptotic abilities as compared with the cells treated by ginkgolides only. Western blot analysis demonstrated that hypothermia (32 or 28 degrees C for 24h) has no effect on the expression of Hypoxia-inducible factor-1 alpha (HIF-1 alpha) protein, suggesting that HIF-1 alpha is not associated with the adverse effect of hypothermia on ginkgolides. The findings imply the importance of further investigating the effects of hypothermia on the pharmacological role or therapeutic efficacy of drugs commonly used clinically.