Effects of prenatal hypoxia on schizophrenia-related phenotypes in heterozygous reeler mice: a gene × environment interaction study.
Effects of prenatal hypoxia on schizophrenia-related phenotypes in heterozygous reeler mice: a gene × environment interaction study.
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DOI：
10.1016/j.euroneuro.2014.05.011
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发表时间：
2014-08
影响因子：
5.6
通讯作者：
Pillai, Anilkumar
中科院分区：
文献类型：
--
作者：
Howell, Kristy R.;Pillai, Anilkumar
遗传和环境因素在精神分裂症的病理生理学中起重要作用。虽然产前缺氧是一个潜在的环境因素牵连在精神分裂症，很少有人知道的后果相结合的遗传风险因素与产前缺氧模型。将杂合reeler（haploinsufficient for reelin; HRM）和野生型（WT）小鼠暴露于产前缺氧（9%氧气两小时）或在胚胎第17天（E17）常氧。在3月龄时进行行为（前脉冲抑制、Y-迷宫和旷场）和功能（额叶皮质和海马的区域体积以及海马血流）测试。分别于E18、1月龄和3月龄检测大鼠额叶皮质和海马组织中缺氧诱导因子1 α（HIF-1α）、血管内皮因子（VEGF）、VEGF受体2（VEGFR 2/Flk 1）和糖皮质激素受体（GR）的水平。此外，还检测了血清VEGF和皮质酮水平。产前缺氧诱导HRM和WT小鼠的焦虑样行为。产前缺氧后海马血流量显著减少，但脑区域体积无变化。胎儿缺氧后，HIF-1α、VEGF、Flk 1和GR的表达均出现明显的年龄和区域依赖性变化。血清VEGF和皮质酮水平下降，产前缺氧。上述产前缺氧引起的变化都没有因reelin缺乏而减轻或加重。这些结果反对缺氧和reelin缺乏之间的任何基因-环境相互作用。
Both genetic and environmental factors play important roles in the pathophysiology of schizophrenia. Although prenatal hypoxia is a potential environmental factor implicated in schizophrenia, very little is known about the consequences of combining models of genetic risk factor with prenatal hypoxia. Heterozygous reeler (haploinsufficient for reelin; HRM) and wild-type (WT) mice were exposed to prenatal hypoxia (9% oxygen for two hr) or normoxia at embryonic day 17 (E17). Behavioral (Prepulse inhibition, Y-maze and Open field) and functional (regional volume in frontal cortex and hippocampus as well as hippocampal blood flow) tests were performed at 3 months of age. The levels of hypoxia and stress-related molecules such as hypoxia-inducible factor-1 α (HIF-1α), vascular endothelial factor (VEGF), VEGF receptor-2 (VEGFR2/Flk1) and glucocorticoid receptor (GR) were examined in frontal cortex and hippocampus at E18, 1 month and 3 months of age. In addition, serum VEGF and corticosterone levels were also examined. Prenatal hypoxia induced anxiety-like behavior in both HRM and WT mice. A significant reduction in hippocampal blood flow, but no change in brain regional volume was observed following prenatal hypoxia. Significant age and region-dependent changes in HIF-1α, VEGF, Flk1 and GR were found following prenatal hypoxia. Serum VEGF and corticosterone levels were found decreased following prenatal hypoxia. None of the above prenatal hypoxia-induced changes were either diminished or exacerbated due to reelin deficiency. These results argue against any gene-environment interaction between hypoxia and reelin deficiency.
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DOI：
10.1176/appi.ajp.2013.12050674
发表时间：
2013-06
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Andreasen NC;Liu D;Ziebell S;Vora A;Ho BC
通讯作者：
Ho BC
影响因子：
3.4
作者：
Duncan, EJ;Szilagyi, S;Rotrosen, JP
通讯作者：
Rotrosen, JP
影响因子：
3.4
作者：
ACRI, JB;MORSE, DE;GRUNBERG, NE
通讯作者：
GRUNBERG, NE
影响因子：
3.7
作者：
Howell KR;Kutiyanawalla A;Pillai A
通讯作者：
Pillai A
影响因子：
5.7
作者：
Asami, Takeshi;Bouix, Sylvain;Whitford, Thomas J.;Shenton, Martha E.;Salisbury, Dean F.;McCarley, Robert W.
通讯作者：
McCarley, Robert W.