In addition this study also showed no obvious increase
In addition, this study also showed no obvious increase in apoptosis but obvious increase in necrosis after WZB117 treatment. The possible reason is that apoptosis is an ATP-utilizing process which is an active and programmed form of cell death. In contrast, necrosis is an uncontrolled or pathological unprogrammed form of cell death (Zong and Thompson, 2006). When intracellular ATP decreased, the pattern of cell death will shift from apoptosis to necrosis (Gramaglia et al., 2004). Thus, although the expression of p53 increased and apoptosis was not obvious. Only a small fraction of NB cells undergoes apoptosis. This result is consistent with other research (Liu et al., 2012).
Conflicts of interest
Introduction Physical exercise is essential for maintaining physical function and health and appears to be important for maintaining cognitive performance in humans. In fact, epidemiological studies demonstrated a reduced risk of mild cognitive impairment and dementia in older adults who maintain higher levels of physical activity [1,2]. Aerobic exercise changes the structure and function of Sodium Orthovanadate regions vulnerable to age-related and disease-related atrophy [3,4], suggesting that physical exercise may improve cognitive performance and could be a therapeutic strategy for neurodegenerative diseases such as dementia. There has been no treatment to halt neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, and dementia with Lewy bodies, to date. Accumulating evidence has revealed that the autophagic system is disrupted and that autophagic substrates, including p62, Keap1 and NBR1, accumulate in the brains of these patients [, , ]. Autophagy is a cellular degradation system that is capable of producing nutrients and energy in response to various conditions, such as nutrient starvation and exercise [8,9]. Because autophagy also serves as a way of efficiently degrading abnormal proteins , activated autophagy could represent a potential therapeutic strategy for diseases that involve abnormally aggregated proteins, including neurodegenerative diseases and lysosomal diseases. Indeed, we previously reported that oral intake of trehalose for a relatively short period (up to 1 week) is sufficient to activate autophagy in the mouse brain. Furthermore, activation of autophagy in the brain can ameliorate neurodegenerative pathology and phenotypes . Therefore, we aimed to more efficiently induce autophagy in the brain and examined the effect of exercise together with trehalose intake on autophagic flow in the mouse brain.
Materials and methods
Discussion Autophagic flux is crucial to maintain physiological functions in various organs and cells and is activated by several factors, such as fasting, and several treatments . We examined the effect of disaccharide and/or exercise on autophagy in this study. Consistent with these lines of evidence [10,19,20], immunoblotting and immunohistochemical analyses demonstrated that a natural saccharide, trehalose, can activate autophagy in the brain, as well as in the liver. Since it is well-known that exercise is also able to activate autophagy, we expected that the synergistic effect of trehalose and exercise on autophagy in the brain. However, contrary to our expectations, immunoblot analysis showed that LC3II levels were decreased in the brain, even in mice fed disaccharides, such as sucrose, maltose or trehalose. Furthermore, despite our extensive efforts to find any effects during exercise, we could not demonstrate any changes in the distribution and staining intensity of LC3 in the brains of mice after exercise. Consistently, a previous study described that autophagy was not induced in the brain, even after 48 h of starvation . Although autophagy is thought to be required for normal turnover of cellular components, particularly in urgent response to starvation and exercise, we have to pay more attention to differences in autophagic response depending on organs and/or cell types.