Zika virus infection during the period of maximal brain growth causes microcephaly and corticospinal neuron apoptosis in wild type mice.
Zika virus infection during the period of maximal brain growth causes microcephaly and corticospinal neuron apoptosis in wild type mice.
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DOI：
10.1038/srep34793
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发表时间：
2016-10-07
影响因子：
4.6
通讯作者：
Page DT
中科院分区：
文献类型：
--
作者：
Huang WC;Abraham R;Shim BS;Choe H;Page DT
孕妇感染寨卡病毒（ZIKV）已被确定为新生儿小头畸形的病因。在此我们检验这样一个假说：大脑快速生长的神经发育阶段特别容易受到寨卡病毒感染的影响。我们在两个不同时间点将寨卡病毒颅内注射到野生型C57BL/6小鼠体内：出生后早期发育阶段，此时大脑以最快速度生长；以及断奶时，此时大脑已基本达到成年大小。两个时间点均显示整个大脑对寨卡病毒和裂解的半胱天冬酶3（CC3，一种细胞凋亡标志物）有广泛的免疫反应。然而，在出生后早期注射寨卡病毒的小鼠中，一些脑区和细胞类型的细胞凋亡增加特别显著，而在年龄较大的动物中我们未观察到这种情况。皮质脊髓锥体神经元是与寨卡病毒感染相关的人类小头畸形所涉及的一种细胞类型，就是此类细胞类型的一个例子。脑室区干细胞区的增殖细胞也减少了。这些发现与大脑快速生长阶段特别容易受到寨卡病毒感染的神经发育影响这一假说相符，并建立了一个有价值的模型，用于研究寨卡病毒感染神经发育影响的潜在机制以及探索候选治疗方法。
Zika virus (ZIKV) infection in pregnant women has been established as a cause of microcephaly in newborns. Here we test the hypothesis that neurodevelopmental stages when the brain is undergoing rapid growth are particularly vulnerable to the effects of ZIKV infection. We injected ZIKV intracranially into wild type C57BL/6 mice at two different time points: early postnatal development, when the brain is growing at its maximal rate, and at weaning, when the brain has largely reached adult size. Both time points showed widespread immunoreactivity for ZIKV and cleaved caspase 3 (CC3, a marker of apoptosis) throughout the brain. However, in early postnatal ZIKV injected mice, some brain areas and cell types display particularly large increases in apoptosis that we did not observe in older animals. Corticospinal pyramidal neurons, a cell type implicated in human microcephaly associated with ZIKV infection, are an example of one such cell type. Proliferating cells in the ventricular zone stem cell compartment are also depleted. These findings are consistent with the hypothesis that periods of rapid brain growth are especially susceptible to neurodevelopmental effects of ZIKV infection, and establish a valuable model to investigate mechanisms underlying neurodevelopmental effects of ZIKV infection and explore candidate therapeutics.
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影响因子：
4.3
作者：
Nowakowski A;Walczak P;Lukomska B;Janowski M
通讯作者：
Janowski M
影响因子：
3.8
作者：
Dowall SD;Graham VA;Rayner E;Atkinson B;Hall G;Watson RJ;Bosworth A;Bonney LC;Kitchen S;Hewson R
通讯作者：
Hewson R
DOI：
10.1056/nejmoa1602412
发表时间：
2016-12-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brasil P;Pereira JP Jr;Moreira ME;Ribeiro Nogueira RM;Damasceno L;Wakimoto M;Rabello RS;Valderramos SG;Halai UA;Salles TS;Zin AA;Horovitz D;Daltro P;Boechat M;Raja Gabaglia C;Carvalho de Sequeira P;Pilotto JH;Medialdea-Carrera R;Cotrim da Cunha D;Abreu de Carvalho LM;Pone M;Machado Siqueira A;Calvet GA;Rodrigues Baião AE;Neves ES;Nassar de Carvalho PR;Hasue RH;Marschik PB;Einspieler C;Janzen C;Cherry JD;Bispo de Filippis AM;Nielsen-Saines K
通讯作者：
Nielsen-Saines K
影响因子：
5.3
作者：
Chen, Youjun;Huang, Wen-Chin;Page, Damon T.
通讯作者：
Page, Damon T.
DOI：
10.4269/ajtmh.16-0111
发表时间：
2016-06-01
期刊：
The American journal of tropical medicine and hygiene
影响因子：
--
作者：
Rossi SL;Tesh RB;Azar SR;Muruato AE;Hanley KA;Auguste AJ;Langsjoen RM;Paessler S;Vasilakis N;Weaver SC
通讯作者：
Weaver SC