Abstract：
Autism spectrum disorder (ASD) is a psychiatric condition characterized by reduced social interaction, anxiety, and stereotypic behaviors related to neuroinflammation and microglia activation. We demonstrated that maternal exposure to Western diet (cafeteria diet or CAF) induced microglia activation, systemic proinflammatory profile, and ASD-like behavior in the offspring. Here, we aimed to identify the effect of alternate day fasting (ADF) as a non-pharmacologic strategy to modulate neuroinflammation and ASD-like behavior in the offspring prenatally exposed to CAF diet. We found that ADF increased plasma beta-hydroxybutyrate (BHB) levels in the offspring exposed to control and CAF diets but not in the cortex (Cx) and hippocampus (Hpp). We observed that ADF increased the CD45 + cells in Cx of both groups; In control individuals, ADF promoted accumulation of CD206 + microglia cells in choroid plexus (CP) and increased in CD45 + macrophages cells and lymphocytes in the Cx. Gestational exposure to CAF diet promoted defective sociability in the offspring; ADF improved social interaction and increased microglia CD206 + in the Hpp and microglia complexity in the dentate gyrus. Additionally, ADF led to attenuation of the ER stress markers (Bip/ATF6/p-JNK) in the Cx and Hpp. Finally, biological modeling showed that fasting promotes higher microglia complexity in Cx, which is related to improvement in social interaction, whereas in dentate gyrus sociability is correlated with less microglia complexity. These data suggest a contribution of intermittent fasting as a physiological stimulus capable of modulating microglia phenotype and complexity in the brain, and social interaction in male mice.
摘要：
自闭症谱系障碍（ASD）是一种以社会交往减少为特征的精神疾病，焦虑,以及与神经炎症和小胶质细胞激活相关的刻板行为。我们证明了母亲暴露于西方饮食（自助餐或CAF）诱导小胶质细胞激活，全身促炎概况，以及后代中类似ASD的行为。这里,我们的目的是确定隔日禁食(ADF)作为一种非药物策略,在产前接受CAF饮食的后代中调节神经炎症和ASD样行为的作用.我们发现，ADF增加了暴露于对照和CAF饮食的后代的血浆β-羟基丁酸（BHB）水平，但在皮质（Cx）和海马（Hpp）中却没有。我们观察到ADF增加了CD45+细胞在Cx的两组;在对照组中,ADF促进脉络丛（CP）中CD206小胶质细胞的积累，并在Cx中CD45巨噬细胞和淋巴细胞中增加。妊娠暴露于CAF饮食会促进后代的社交能力缺陷；ADF改善了社交互动，并增加了Hpp中的小胶质细胞CD206和齿状回中的小胶质细胞复杂性。此外,ADF导致Cx和Hpp中ER应激标志物(Bip/ATF6/p-JNK)的衰减。最后,生物建模表明，禁食促进Cx中更高的小胶质细胞复杂性，这与社会互动的改善有关，而在齿状回中，社交能力与较少的小胶质细胞复杂性相关。这些数据表明，间歇性禁食是一种能够调节小胶质细胞表型和大脑复杂性的生理刺激，和雄性小鼠的社会互动。
