Prenatal and early life exposure to air pollution induced hippocampal vascular leakage and impaired neurogenesis in association with behavioral deficits.
Prenatal and early life exposure to air pollution induced hippocampal vascular leakage and impaired neurogenesis in association with behavioral deficits.
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DOI：
10.1038/s41398-018-0317-1
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发表时间：
2018-11-29
影响因子：
6.8
通讯作者：
Morgan TE
中科院分区：
文献类型：
--
作者：
Woodward NC;Haghani A;Johnson RG;Hsu TM;Saffari A;Sioutas C;Kanoski SE;Finch CE;Morgan TE
暴露于与交通相关的空气污染(TRAP)与人类一系列神经发育障碍有关。在啮齿动物模型中，出生前暴露于陷阱会增加抑郁行为，并增加大脑小胶质细胞的活动。为了确定细胞机制，我们检查了成年神经发生和血脑屏障(BBB)与认知和动机行为的关系，这些大鼠从怀孕到成年一直暴露在纳米尺寸的TRAP亚成分中。在5个月大时，暴露的雄性大鼠在海马齿状回(DG)中新生的神经元减少了70%。小胶质细胞在DG和CA1区被激活(IBA1增加35%)。血脑屏障改变，CA1层紧密连接蛋白ZO-1减少75%，铁沉积增加两倍，这是微出血的标志。暴露的大鼠背景记忆受损(背景中的新对象)，觅食行为减少，抑郁行为增加(强迫游泳)。新生神经发生缺陷与抑郁行为呈负相关，而微出血增加与背景记忆缺陷呈负相关。这些发现提供了第一个证据，表明产前和早期接触TRAP会损害成年海马神经发生，并增加与行为缺陷相关的微量出血。
Exposure to traffic-related air pollution (TRAP) is associated with a range of neurodevelopmental disorders in human populations. In rodent models, prenatal TRAP exposure increased depressive behaviors and increased brain microglial activity. To identify cellular mechanisms, we examined adult neurogenesis and the blood–brain barrier (BBB) in relation to cognition and motivated behaviors in rats that were exposed to a nano-sized TRAP subfraction from gestation into adulthood. At age 5 months, exposed male rats had 70% fewer newly generated neurons in the dentate gyrus (DG) of the hippocampus. Microglia were activated in DG and CA1 subfields (35% more Iba1). The BBB was altered, with a 75% decrease of the tight junction protein ZO-1 in the CA1 layer, and twofold more iron deposits, a marker of microhemorrhages. The exposed rats had impaired contextual memory (novel object in context), reduced food-seeking behavior, and increased depressive behaviors (forced swim). Deficits of de novo neurogenesis were inversely correlated with depressive behavior, whereas increased microbleeds were inversely correlated with deficits in contextual memory. These findings give the first evidence that prenatal and early life exposure to TRAP impairs adult hippocampal neurogenesis and increases microbleeds in association with behavioral deficits.
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影响因子：
10.4
作者：
Kalkbrenner AE;Windham GC;Zheng C;McConnell R;Lee NL;Schauer JJ;Thayer B;Pandey J;Volk HE
通讯作者：
Volk HE
影响因子：
3.7
作者：
Davis DA;Bortolato M;Godar SC;Sander TK;Iwata N;Pakbin P;Shih JC;Berhane K;McConnell R;Sioutas C;Finch CE;Morgan TE
通讯作者：
Morgan TE
影响因子：
9.3
作者：
Cheng H;Davis DA;Hasheminassab S;Sioutas C;Morgan TE;Finch CE
通讯作者：
Finch CE
影响因子：
3.8
作者：
Klocke, Carolyn;Allen, Joshua L.;Cory-Slechta, Deborah A.
通讯作者：
Cory-Slechta, Deborah A.
影响因子：
10.4
作者：
Allen JL;Conrad K;Oberdörster G;Johnston CJ;Sleezer B;Cory-Slechta DA
通讯作者：
Cory-Slechta DA