High-Fat Diet Exacerbates Behavioral and Neurochemical Deficits in BTBR Mice: Linking Intestinal Inflammation and...

This study aims to investigate the effects of high-fat diet (HFD) on behavioral symptoms, brain neurotransmitters and intestinal inflammation in autism spectrum disorders (ASD) model mice-BTBR T⁺tf/J (BTBR) mice, and the effect of melatonin intervention. In a two-phase design, when investigating the effects of HFD, 16 C57 mice and 16 BTBR mice were divided into two groups and subjected to HFD or normal diet (ND) for 4 weeks; when investigating the effects of melatonin, 32 BTBR mice were divided into two groups and subjected to HFD or ND for 4 weeks, followed by melatonin or vehicle treatment for another 2 weeks. Behavioral assessments were performed at post-intervention phases, followed with determination of brain neurotransmitters-serotonin (5-hydroxy tryptamine, 5-HT) and dopamine (DA), and gastrointestinal inflammatory mediator analysis. Our findings demonstrate that HFD exacerbates anxiety-like behaviors and social deficits which may be mediated through brain neurotransmitter and gut, characterized by concomitant decrease of cerebral 5-HT and DA stores, coupled with intestinal inflammation. Meanwhile, melatonin administration effectively ameliorated ASD-like behavior, increased 5-HT and DA expressive levels in brain tissues and attenuated intestinal inflammation in HFD BTBR mice.