Autism Spectrum Disorders (ASD) are neurodevelopmental disorders characterized by social communication deficits and repetitive/stereotyped behaviours. We evaluated the effects of a chronic treatment with the immunomodulator drug Fingolimod (FTY720 - a non-selective Sphingosine 1-Phosphate Receptor ligand) in an ASD model, the BTBR T+tf/J (BTBR) mouse strain. In adult BTBR males, chronic FTY720 treatment (4 weeks) increased social and vocal response during a male-female interaction and hippocampal expression of BDNF and Neuregulin 1, two trophic factors reduced in BTBR when compared to control C57 mice. FTY720 also re-established the expression of IL-1β and MnSOD in the hippocampus, whereas it did not modify IL-6 mRNA content. In addition to its central effect, FTY720 modulated the activation state of peripheral macrophages in the BTBR model, both in basal conditions and after stimulation with an immune challenge. Furthermore, IL-6 mRNA colonic content of BTBR mice, reduced when compared with C57 mice, was normalized by chronic treatment with FTY720. Our study, while indicating FTY720 as a tool to attenuate relevant alterations of the BTBR neurobehavioural phenotype, emphasizes the importance of gut mucosal immune evaluation as an additional target that deserve to be investigated in preclinical studies of anti-inflammatory therapeutic approaches in ASD.

中文翻译：

---

芬戈莫德对自闭症BTBR小鼠模型中的社交互动，中枢神经系统和外周免疫反应的有益作用。

自闭症谱系障碍（ASD）是神经发育障碍，特征是社交沟通不足和重复性/刻板印象的行为。我们在ASD模型BTBR T + tf / J（BTBR）小鼠品系中评估了使用免疫调节剂芬戈莫德（FTY720-非选择性鞘氨醇1-磷酸受体配体）进行长期治疗的效果。在成年BTBR雄性中，慢性FTY720治疗（4周）在男女互动以及BDNF和神经调节蛋白1海马表达期间增加了社交和声音反应，与对照C57小鼠相比，BTBR减少了两个营养因子。FTY720还重新建立了海马中IL-1β和MnSOD的表达，而它并未改变IL-6 mRNA的含量。除了发挥中心作用外，FTY720还调节了BTBR模型中外周巨噬细胞的激活状态，无论是在基础条件下还是在受到免疫刺激后。此外，与C57小鼠相比，BTBR小鼠的IL-6 mRNA结肠含量降低了，可通过FTY720的长期治疗使其正常化。我们的研究虽然表明FTY720是减轻BTBR神经行为表型相关变化的一种工具，但强调了肠道粘膜免疫评估的重要性，它是在ASD抗炎治疗方法的临床前研究中值得研究的另一个目标。