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Neonatal immune challenge induces female-specific changes in social behavior and somatostatin cell number
Brain, Behavior, and Immunity ( IF 15.1 ) Pub Date : 2020-11-01 , DOI: 10.1016/j.bbi.2020.08.013
Caroline J Smith 1 , Marcy A Kingsbury 2 , Julia E Dziabis 1 , Richa Hanamsagar 1 , Karen E Malacon 1 , Jessica N Tran 2 , Haley A Norris 2 , Mary Gulino 2 , Evan A Bordt 2 , Staci D Bilbo 1
Affiliation  

Decreases in social behavior are a hallmark aspect of acute "sickness behavior" in response to infection. However, immune insults that occur during the perinatal period may have long-lasting consequences for adult social behavior by impacting the developmental organization of underlying neural circuits. Microglia, the resident immune cells of the central nervous system, are sensitive to immune stimulation and play a critical role in the developmental sculpting of neural circuits, making them likely mediators of this process. Here, we investigated the impact of a postnatal day (PND) 4 lipopolysaccharide (LPS) challenge on social behavior in adult mice. Somewhat surprisingly, neonatal LPS treatment decreased sociability in adult female, but not male mice. LPS-treated females also displayed reduced social interaction and social memory in a social discrimination task as compared to saline-treated females. Somatostatin (SST) interneurons within the anterior cingulate cortex (ACC) have recently been suggested to modulate a variety of social behaviors. Interestingly, the female-specific changes in social behavior observed here were accompanied by an increase in SST interneuron number in the ACC. Finally, these changes in social behavior and SST cell number do not appear to depend on microglial inflammatory signaling, because microglia-specific genetic knock-down of myeloid differentiation response protein 88 (MyD88; the removal of which prevents LPS from increasing proinflammatory cytokines such as TNFα and IL-1β) did not prevent these LPS-induced changes. This study provides novel evidence for enduring effects of neonatal immune activation on social behavior and SST interneurons in females, largely independent of microglial inflammatory signaling.

中文翻译:

新生儿免疫挑战诱导社会行为和生长抑素细胞数量的女性特异性变化

社会行为的减少是对感染作出反应的急性“病态行为”的一个标志性方面。然而,围产期发生的免疫损伤可能会影响基础神经回路的发育组织,从而对成人社会行为产生长期影响。小胶质细胞是中枢神经系统的常驻免疫细胞,对免疫刺激敏感,并在神经回路的发育塑造中发挥关键作用,使它们可能成为这一过程的中介。在这里,我们调查了产后一天 (PND) 4 脂多糖 (LPS) 挑战对成年小鼠社交行为的影响。有点令人惊讶的是,新生 LPS 治疗降低了成年雌性小鼠的社交能力,但雄性小鼠没有。与盐水处理的女性相比,LPS 处理的女性在社会歧视任务中也表现出减少的社会互动和社会记忆。最近有人建议前扣带皮层 (ACC) 内的生长抑素 (SST) 中间神经元调节各种社会行为。有趣的是,这里观察到的女性特定社会行为变化伴随着 ACC 中 SST 中间神经元数量的增加。最后,社会行为和 SST 细胞数量的这些变化似乎并不依赖于小胶质细胞炎症信号,因为小胶质细胞特异性基因敲除骨髓分化反应蛋白 88(MyD88;去除它可以防止 LPS 增加促炎细胞因子,例如TNFα 和 IL-1β) 不能阻止这些 LPS 诱导的变化。
更新日期:2020-11-01
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