Lycopene improves social disorder and reduces hippocampal inflammation in BTBR mice

Abstract

Objective To investigate the effects of lycopene (Lyc) on hippocampal inflammation, social deficits and repetitive stereotyped behaviors in BTBR T+ Itpr3tf/J autistic mice (BTBR, a mouse strain showing lower sociability as a model for autism spectrum disorder). Methods Adult male C57BL/6J (C57) and BTBR mice aged 7-8 weeks were randomly divided into (n=8): C57+Veh group, C57+Lyc group, BTBR+Veh group and BTBR+Lyc group. The mice from the C57+Lyc group and BTBR+Lyc group were given 20 mg/kg Lyc by gavage once a day for 7 d, and those of the C57+Veh group and BTBR+Veh mice were given equal volume of corn oil. Then three-chamber social test, male-female reciprocal social interactions, self-grooming, marble buying, open field test, object recognition test, nest building, and Y-maze test were conducted in these mice. Immediately after the behavioral tests, the mice were sacrificed and their brain samples were harvested for RT-qPCR and Western blotting. Results Behavioral results showed that in the three-chamber social test, the mice of the BTBR+Veh group spent longer time in the chamber with the object, showing much curiosity about the object (P < 0.05), while the mice after Lyc treatment showed a preference for strange mice (P < 0.05). In the self-grooming and marble burying behavior test, the BTBR+Veh group showed markedly increased repeated stereotyped behaviors than the C57+Veh group mice (P < 0.05), which could be alleviated by Lyc treatment (P < 0.05). The hippocampal expression of NLRP3 at mRNA and protein levels (P < 0.05), and the mRNA levels of IL-1β, IL-18, IL-6, NF-κB, and TNF-α were significantly increased in the BTBR+Veh group mice when compared with the C57+Veh group mice, and Lyc treatment obviously reversed above changes (P < 0.05). Conclusion Lyc treatment improves three-chamber social deficits and repetitive stereotyped behaviors in BTBR mice by reducing NLRP3 inflammasome in the hippocampus of BTBR mice.

Keywords

• lycopene
• autism
• nlrp3 inflammasome
• hippocampus
• social communication disorder