Hepatic Alterations in a BTBR T + Itpr3tf/J Mouse Model of Autism and Improvement Using Melatonin via Mitigation Oxidative Stress, Inflammation and Ferroptosis.

Scientists studied liver problems in mice that model autism behaviors. They found these mice had slower liver development, iron buildup, and increased harmful stress in liver cells. When given melatonin (a natural hormone), the mice's liver health improved. This suggests that liver problems might be part of autism and that melatonin could potentially help, though more research in humans is needed.

This preclinical study examined liver abnormalities in BTBR mice, an established autism model, and tested melatonin as a potential therapeutic intervention. Researchers found that BTBR mice exhibited retarded liver development, iron accumulation, elevated oxidative stress, inflammation, and altered ferroptosis markers compared to control mice. The study demonstrated upregulation of NFR2 and downregulation of KEAP1, indicating disrupted cellular stress responses. Melatonin treatment showed positive effects on liver structure and metabolic function in the autism model mice, suggesting potential therapeutic benefits through reduction of oxidative stress, inflammation, and ferroptosis pathways.

Results suggest autism may involve liver dysfunction beyond neurological symptoms. Melatonin shows promise as therapeutic intervention for systemic complications, but human studies needed before clinical application. Liver health monitoring may warrant consideration in autism care.

Animal study using single autism mouse model limits human applicability. Sample size not reported. Study design unclear. Findings require replication in human studies before clinical translation.

Autism spectrum disorder (ASD) is a complicated neurodevelopmental disorder, and its etiology is not well understood. It is known that genetic and nongenetic factors determine alterations in several organs, such as the liver, in individuals with this disorder. The aims of the present study were to analyze morphological and biological alterations in the liver of an autistic mouse model, BTBR T + Itpr3tf/J (BTBR) mice, and to identify therapeutic strategies for alleviating hepatic impairments using melatonin administration. We studied hepatic cytoarchitecture, oxidative stress, inflammation and ferroptosis in BTBR mice and used C57BL6/J mice as healthy control subjects.

The mice were divided into four groups and then treated and not treated with melatonin, respectively. BTBR mice showed (a) a retarded development of livers and (b) iron accumulation and elevated oxidative stress and inflammation. We demonstrated that the expression of ferroptosis markers, the transcription factor nuclear factor erythroid-related factor 2 (NFR2), was upregulated, and the Kelch-like ECH-associated protein 1 (KEAP1) was downregulated in BTBR mice. Then, we evaluated the effects of melatonin on the hepatic alterations of BTBR mice; melatonin has a positive effect on liver cytoarchitecture and metabolic functions.