PolyI:C Maternal Immune Activation on E9.5 Causes the Deregulation of Microglia and the Complement System in Mice, Leading to Decreased Synaptic Spine Density

被引:0
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作者
Yan, Shuxin [1 ]
Wang, Le [1 ,2 ]
Samsom, James Nicholas [1 ]
Ujic, Daniel [1 ,3 ]
Liu, Fang [1 ,3 ,4 ,5 ]
机构
[1] Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, 250 Coll St, Toronto, ON M5T 1R8, Canada
[2] Wenzhou Med Univ, Inst Mental Hlth & Drug Discovery, Sch Mental Hlth, Oujiang Lab,Zhejiang Lab Regenerat Med Vis & Brain, Wenzhou 325000, Peoples R China
[3] Univ Toronto, Inst Med Sci, 1 Kings Coll Cir, Toronto, ON M5S 1A8, Canada
[4] Univ Toronto, Dept Psychiat, 250 Coll St, Toronto, ON M5T 1R8, Canada
[5] Univ Toronto, Dept Physiol, 1 Kings Coll Cir, Toronto, ON M5S 1A8, Canada
基金
加拿大健康研究院;
关键词
maternal immune activation; synaptic pruning; dendritic spine density; microglia; complement; PREFRONTAL CORTEX; YOLK-SAC; CHALLENGE; INFECTION; BRAIN; RISK; HIPPOCAMPUS; INCREASES; EXPOSURE; NEURONS;
D O I
10.3390/ijms25105480
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Maternal immune activation (MIA) is a risk factor for multiple neurodevelopmental disorders; however, animal models developed to explore MIA mechanisms are sensitive to experimental factors, which has led to complexity in previous reports of the MIA phenotype. We sought to characterize an MIA protocol throughout development to understand how prenatal immune insult alters the trajectory of important neurodevelopmental processes, including the microglial regulation of synaptic spines and complement signaling. We used polyinosinic:polycytidylic acid (polyI:C) to induce MIA on gestational day 9.5 in CD-1 mice, and measured their synaptic spine density, microglial synaptic pruning, and complement protein expression. We found reduced dendritic spine density in the somatosensory cortex starting at 3-weeks-of-age with requisite increases in microglial synaptic pruning and phagocytosis, suggesting spine density loss was caused by increased microglial synaptic pruning. Additionally, we showed dysregulation in complement protein expression persisting into adulthood. Our findings highlight disruptions in the prenatal environment leading to alterations in multiple dynamic processes through to postnatal development. This could potentially suggest developmental time points during which synaptic processes could be measured as risk factors or targeted with therapeutics for neurodevelopmental disorders.
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页数:14
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