| Autor: |
Rezzani R; Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy.; Interdipartimental University Center of Research 'Adaption and Regeneration of Tissues and Organs (ARTO)', University of Brescia, 25123 Brescia, Italy.; Italian Society for the Study of Orofacial Pain (Società Italiana Studio Dolore Orofacciale-SISDO), 25123 Brescia, Italy., Gianò M; Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy., Pinto D; Human Microbiome Advanced Project Institute, 20129 Milan, Italy., Rinaldi F; Human Microbiome Advanced Project Institute, 20129 Milan, Italy., van Noorden CJF; Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia., Favero G; Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy.; Interdipartimental University Center of Research 'Adaption and Regeneration of Tissues and Organs (ARTO)', University of Brescia, 25123 Brescia, Italy. |
| Abstrakt: |
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. |
