Centre for Behavioral Sciences and Mental Health, Italian National Institute of Health (ISS), Rome, Italy.
Gastroenterology Unit IRCCS "Casa Sollievo della Sofferenza", Hospital San Giovanni Rotondo, Foggia, Italy.
Transl Psychiatry. 2022 Sep 14;12(1):384. doi: 10.1038/s41398-022-02149-9.
Autism Spectrum Disorder (ASD) is a sex-biased neurodevelopmental disorder with a male to female prevalence of 4:1, characterized by persistent deficits in social communication and interaction and restricted-repetitive patterns of behavior, interests or activities. Microbiota alterations as well as signs of neuroinflammation have been also reported in ASD. The involvement of immune dysregulation in ASD is further supported by evidence suggesting that maternal immune activation (MIA), especially during early pregnancy, may be a risk factor for ASD. The present study was aimed at characterizing the effects of MIA on behavior, gut microbiota and neuroinflammation in the mouse offspring also considering the impact of MIA in the two sexes. MIA offspring exhibited significant ASD-like behavioral alterations (i.e., deficits in sociability and sensorimotor gating, perseverative behaviors). The analysis of microbiota revealed changes in specific microbial taxa that recapitulated those seen in ASD children. In addition, molecular analyses indicated sex-related differences in the neuroinflammatory responses triggered by MIA, with a more prominent effect in the cerebellum. Our data suggest that both sexes should be included in the experimental designs of preclinical studies in order to identify those mechanisms that confer different vulnerability to ASD to males and females.
自闭症谱系障碍（ASD）是一种与性别相关的神经发育障碍，男性患病率是女性的 4 倍，其特征是社会交往和互动方面持续存在缺陷，以及行为、兴趣或活动的受限和重复模式。ASD 中也报道了微生物组的改变和神经炎症的迹象。免疫失调参与 ASD 的证据进一步表明，母体免疫激活（MIA），特别是在怀孕早期，可能是 ASD 的一个风险因素。本研究旨在描述 MIA 对雄性和雌性小鼠后代行为、肠道微生物群和神经炎症的影响，同时考虑 MIA 在两种性别中的影响。MIA 后代表现出明显的 ASD 样行为改变（即社交和感觉门控缺陷，持续行为）。微生物组分析显示，特定微生物类群发生了变化，这些变化再现了 ASD 儿童的变化。此外，分子分析表明，MIA 引发的神经炎症反应存在性别相关差异，小脑的影响更为明显。我们的数据表明，在进行临床前研究的实验设计时，应该同时纳入雄性和雌性，以确定那些导致 ASD 对男性和女性易感性不同的机制。
