As imply 6 SEM. *, p,0.05 vs. TD, TD+CUS, TD+CUS+ME, TD+CUS+IE; , C; , TD; #, TD+CUS; m, TD+CUS+ME; g, TD+CUS+ IE. doi:10.1371/journal.pone.0066996.gNthe non-stressed mice fed a typical diet, as reported inside a earlier study [20]. The mice fed a TD diet regime showed considerably higher sucrose preference than the C mice (p,0.05) (F [4, 48] = 5.592; P,0.001) (Fig. 4b). These findings recommended that TD could enhance sucrose preference with or without having chronic pressure. To examine the effect of TD feeding and CUS on understanding and memory, all mice were subjected to ORT in the 4th week on the experiment. C mice showed a strong preference to get a novel object, whereas TD and TD+CUS mice showed a drastically decreased preference for a novel object compared with the C mice. There was no important distinction among C, TD+CUS+ME and TD+CUS+IE mice. Also, TD+CUS+ME and TD+CUS+IE mice showed a substantially stronger preference to get a novel object than TD mice (F [4,45] = five.701; P,0.001) (Fig. 5). These findings recommended that the impairment of cognitive ability was attributable not to CUS but to TD, and that frequent physical exercise, whether or not moderate or intense, prevented the impairment of finding out and memory.PLOS A single | www.plosone.Sutimlimab orgExercise Prevents Depression in TD MiceFigure four.Pegaptanib sodium Effects of tryptophan deficiency, CUS and common physical exercise in FST (a) and SFT (b).PMID:23514335 Information are expressed as imply six SEM. *, p,0.05 vs. C; 1, p,0.05 vs. TD; #, p,0.05 vs. TD+CUS; {, p,0.05 vs. TD+CUS+ME. doi:10.1371/journal.pone.0066996.gFigure 5. Effects of tryptophan deficiency, CUS and regular exercise on recognition index in object recognition. Data are expressed as mean 6 SEM. *, p,0.05 vs. C; #, p,0.05 vs. TD. doi:10.1371/journal.pone.0066996.gMoreover, we exposed the mice to PAT for examination of the effects of TD and CUS on long-term memory. When latency to reenter the dark compartment was measured before CUS treatment, all the groups of mice showed equal values (over 200 sec). Subsequently, C mice maintained constant latency to reenter the dark compartment when it was re-measured on the 7th, 14th and 30th days after the training day. In contrast, other groups of mice showed gradual decreases in latency and showed significantly decreased latency compared with C mice on the 30th day (F [4, 46] = 4.697; P,0.003) (Fig. 6). These findings suggested that the impairment of long-term memory is attributable not to CUS but to TD, and that regular exercise, whether moderate or intense, does not prevent the impairment of long-term memory.3. Immunohistochemical ResultsThe number of Ki67-positive cells, which were used as a marker of proliferating cells [26,27], was significantly lower in TD+CUS mice than in the other mice (F [4,42] = 4.664; P,0.003) (Fig. 7). No significant difference was discerned, except for TD+CUS mice (Fig. 7). On the other hand, the mice fed on TD showed a significantly lower number of BrdU-positive cells than C mice (F [4,39] = 37.78; P,0.001) (Fig. 8). However, comparison among those fed a TD diet revealed that TD+CUS+ME and TD+CUS+IE mice showed significantly higher numbers of BrdU-positive cells than TD and TD+CUS (Fig. 8).DiscussionTo investigate the causal relationship between the level of brain 5-HT and prevention of depression-like behavior via regularPLOS ONE | www.plosone.orgexercise, we examined depression-like behavior, brain 5-HT, proliferation and survival of newly born cells in hippocampus, and learning and memory using the mice fed a TD diet and subjec.