Abstract:

Objective To investigate the effect and mechanism of caloric restriction (CR) on early social isolation (SI) induced cognitive dysfunction in mice. Methods Thirty-six kunming mice (3-weeks old) were randomly divided into group house (GH, n=12), early socially isolated (SI, n=12), caloric restriction and socially isolated (SI+CR, n=12).The GH group (6 mice/cage) and SI group (1 mice/cage) were reared separately under the same conditions, while the SI+CR group (1 mice/cage) were given food every other day. The open field experiment was used to measure the locomotive of mice; The object recognition task was used to evaluate the cognitive function; The expression of microglial marker ionized calcium-binding adapter molecule 1 (IBA-1) in hippocampus was detected by immunohistochemistry. The expression of microglial activation marker CD68 and interleukin-1β (IL-1β) in hippocampus was detected by Western blotting. Results In the open field test, there was no difference in the activity of the three groups of mice. Compared with the GH group, the SI group showed significantly reduced discrimination ratio in object recognition task, with remarkably up-regulated expression of IL-1β in hippocampus (P<0.01). In addition, SI group exhibited over-activated microglia in hippocampus indicated by increased number of IBA-1-positive cells and high expression of CD68 (P<0.01). Compared with the SI group, SI+CR group enhanced discrimination ratio in object recognition task, with down-regulated expression of IL-1β in hippocampus (P<0.01), and the number of IBA-1-positive cells and the expression of CD68 significantly reduced (P<0.01). Conclusion Caloric restriction alleviates SI-induced cognitive dysfunction, which might be attributed to the inhibiting of microglia activation in the hippocampus.

Key words: Early social isolation, Caloric restriction, Cognitive dysfunction, Microglia, Hippocampus, Western blotting, Mouse