Objective To investigate the effects of caloric restriction on the adaptive ability of mice of different ages to novel environments and to explore its relationship with hippocampal autophagic activity.
Methods A total of 120 newly weaned C57BL/6 mice were randomly divided into an ad libitum feeding group (AL) and a caloric restriction group (CR). The food intake of the CR group was 70% of that of the AL group of the same age. Fifteen mice were randomly selected from each group at the ages of 1.5, 3, 12, and 20 months and were sacrificed and sampled after the open-field experiments. The levels of autophagy and ubiquitinated proteins in the hippocampus were examined by Western blot and immunohistochemical staining.
Results CR delayed the age related decline in the ability to adapt to novel environments in adult mice, as reflected in the distance travelled in the open field, the duration of activity in the central zone, and the number of uprights (CR
12m>AL
12m,
P<0.05; CR
20m>AL
20m,
P<0.01）. However, there were adverse effects on the ability to adapt to novel environments in juvenile mice, as evidenced by the distance travelled in the open field (CR
3m<AL
3m,
P<0.05）, central district activity hours (CR
1.5m<AL
1.5m,
P<0.01; CR
3m<AL
3m,
P<0.05）. CR significantly activated hippocampal autophagy in adult mice（LC3II/LC3I,beclin1：CR
12m>AL
12m, CR
20m>AL
20m;p62：CR
20m<AL
20m.
P<0.05）and accelerated the clearance of ubiquitinated proteins（Ub, Ub-IOD:CR
12m<AL
12m,CR
20m<AL
20m.
P<0.05). However, in young mice, CR significantly increased LC3II/LC3I and p62 expression at 3 months of age(p62:CR
1.5m>AL
1.5m,CR
3m>AL
3m.
P<0.05).
Conclusion After hippocampal maturation, autophagy is activated by caloric restriction to maintain the stability of the neuronal environment, which is beneficial to brain health. Although caloric restriction in infancy activates the formation of hippocampal autophagosomes, it inhibits the degradation efficiency of autophagy, which is detrimental to the development of cognitive function.
Key words
caloric restriction /
hippocampus /
autophagy /
aging /
open feild test
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