Effects of Sucrose Solution Intake during Growth Period on Social Aggression and Inflammatory Response in Adult Mice

Abstract

Aggressive behavior has been traditionally defined as an overt behavior with the intention of inflicting physical damage on other individual. Alt-hough aggression has advantages in competitive situations for obtaining food or defending territories and mates from competitors in wild animal, it has been considered as one of the major social problems in the human society. Among extrinsic factors which are considered to affect aggres-sive behaviors, the association between specific food component in the diet such as sugar and aggressive behaviors has been suggested. Sugars are found in diet either as a natural component of the food or as an add-ed sugar of foods and beverages. Although added sugar enhances food desirability by sweetening foods and beverages, it provides only empty calories with no nutrient value. Although overconsumption of sugar-sweetened beverages (SSBs) is widely known to be a key contributor to epidemic of overweight and obesity, its effects on behavioral changes have not been fully studied yet. In present study, we examined the long-term effects of SSB on social aggression in mice. 3 week old weaned mice started to drink either 30 w/v% of sucrose solution (S30), plain wa-ter (CT), or aspartame solution with equivalent sweetness of the sucrose solution (A30) until they grew to 11 week old adult. Resident-intruder test revealed the total duration spent on any of six different aggressive behav-iors- biting, sexual mounting, clinch, lateral threat and upright was signif-icantly longer in S30 than any other groups. The transcriptome analysis of brain tissues presented the gene expression profiles of S30 were readi-ly distinguished from those of CT or A30 in principal component analysis (PCA). Differentially expressed genes in S30 compared to CT or A30 were categorized on their biological functions and top 6 significant cate-gories were all related to immunological disorders. Bioinformatic analysis of upstream regulator molecules that control target gene expressions iden-tified Tlr4, Stat4, Chuk and Il1b that lead to inflammatory responses in mice of S30. Heightened levels of corticosterone, an analogue of cortisol for rodents, was observed in S30 and the dramatic increase in the number of CD11b+Gr-1+ cells was observed in the same group by FACS analysis. Furthermore, corticosterone resistance was found in mice of S30. Inter-estingly, the artificial sweetener failed to mimic the roles of sugar in ele-vating corticosterone and promoting social aggression. Taken together, these results demonstrate long-term SSB consumption promotes aggres-sive behaviors, and also inflammatory response in brain and corti-costerone resistance mediate the roles played by sugar in promoting so-cial aggression. Our studies provide information useful for development of intervening strategies to control social aggression for public health.