Neonatal immune challenge induces female-specific changes in social behavior and somatostatin cell number.
Neonatal immune challenge induces female-specific changes in social behavior and somatostatin cell number.
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DOI：
10.1016/j.bbi.2020.08.013
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Bilbo SD
中科院分区：
文献类型：
--
作者：
Smith CJ;Kingsbury MA;Dziabis JE;Hanamsagar R;Malacon KE;Tran JN;Norris HA;Gulino M;Bordt EA;Bilbo SD
社交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，在围产期发生的免疫损伤可能会影响潜在神经回路的发育组织，从而对成年人的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，使其成为这一过程的介质。在这里，我们研究了出生后第4天（PND）脂多糖（LPS）挑战对成年小鼠社会行为的影响。有些令人惊讶的是，新生儿LPS治疗降低了成年雌性小鼠的社交能力，但对雄性小鼠没有影响。LPS处理的女性还显示减少社会交往和社会记忆的社会歧视任务相比，盐水处理的女性。前扣带皮层（ACC）内的生长抑素（SST）中间神经元最近被认为调节各种社会行为。有趣的是，这里观察到的女性特有的社会行为变化伴随着ACC中SST中间神经元数量的增加。最后，这些社会行为和SST细胞数量的变化似乎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低髓样分化反应蛋白88（MyD 88;去除MyD 88可防止LPS增加促炎细胞因子，如TNFα和IL-1β）并不能防止这些LPS诱导的变化。这项研究为新生儿免疫激活对女性社会行为和SST中间神经元的持久影响提供了新的证据，在很大程度上独立于小胶质细胞炎症信号。
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.
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影响因子：
64.8
作者：
Filiano AJ;Xu Y;Tustison NJ;Marsh RL;Baker W;Smirnov I;Overall CC;Gadani SP;Turner SD;Weng Z;Peerzade SN;Chen H;Lee KS;Scott MM;Beenhakker MP;Litvak V;Kipnis J
通讯作者：
Kipnis J
影响因子：
3.8
作者：
Bicks LK;Koike H;Akbarian S;Morishita H
通讯作者：
Morishita H
DOI：
10.1016/j.bbi.2016.07.152
发表时间：
2016-11
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Doenni VM;Gray JM;Song CM;Patel S;Hill MN;Pittman QJ
通讯作者：
Pittman QJ
自闭症谱系障碍（ASD）、精神分裂症和双相情感障碍中全转录组异构体水平失调
影响因子：
56.9
作者：
Gandal, Michael J.;Zhang, Pan;Geschwind, Daniel H.
通讯作者：
Geschwind, Daniel H.
影响因子：
6.2
作者：
Hanamsagar R;Alter MD;Block CS;Sullivan H;Bolton JL;Bilbo SD
通讯作者：
Bilbo SD