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.
Int J Mol Sci. 2024 Jan 16;25(2):1086. doi: 10.3390/ijms25021086.
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.
自闭症谱系障碍（ASD）是一种复杂的神经发育障碍，其病因尚不清楚。已知遗传和非遗传因素决定了患有这种疾病的个体的几个器官（如肝脏）发生改变。本研究的目的是分析自闭症小鼠模型 BTBR T + Itpr3tf/J（BTBR）小鼠的肝脏形态和生物学变化，并使用褪黑素给药来确定缓解肝损伤的治疗策略。我们研究了 BTBR 小鼠的肝细胞结构、氧化应激、炎症和铁死亡，并使用 C57BL6/J 小鼠作为健康对照。将小鼠分为四组，然后分别用褪黑素处理和未处理。BTBR 小鼠表现出（a）肝脏发育迟缓，（b）铁积累和氧化应激及炎症升高。我们表明，铁死亡标志物的表达，转录因子核因子红细胞相关因子 2（NFR2）上调，BTBR 小鼠中的 Kelch 样 ECH 相关蛋白 1（KEAP1）下调。然后，我们评估了褪黑素对 BTBR 小鼠肝脏改变的影响；褪黑素对肝细胞结构和代谢功能有积极影响。
