Oculomotor deficits in aryl hydrocarbon receptor null mouse.
Oculomotor deficits in aryl hydrocarbon receptor null mouse.
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DOI：
10.1371/journal.pone.0053520
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Beraneck M
中科院分区：
文献类型：
--
作者：
Chevallier A;Mialot A;Petit JM;Fernandez-Salguero P;Barouki R;Coumoul X;Beraneck M
芳烃受体（Aryl hydrocarbon Receptor，AhR）是一种配体激活的转录因子，它介导了多种环境污染物如2，3，7，8-四氯二苯并-对-二恶英（TCDD）的毒性和致癌作用。最近在秀丽隐杆线虫和黑腹果蝇中的研究表明，AhR的直系同源物仅在某些类型的神经元中表达，并与中枢神经系统的发育和稳态有关。虽然AhR的生理作用在哺乳动物的心脏，肝脏和配子发生中被证明，但其个体发生的表达和推定的神经功能仍然难以捉摸。在这里，我们报告成年小鼠AhR的组成性缺失（AhR-/-）导致自发性摆动水平眼球震颤形式的异常眼球运动。为了确定眼球震颤是前庭、视觉还是小脑起源，研究了凝视稳定反射，即前庭眼反射和视动反射（VOR和OKR）。OKR在AhR−/−小鼠中的效果较差，表明视觉运动回路存在缺陷，而VOR受到轻度影响。此外，AhR在视网膜神经节细胞发育过程中表达，但视网膜电图显示视网膜细胞功能无损害。AhR−/−小鼠的小脑结构是正常的，这与保留的VOR适应是相容的，这是一种依赖于小脑完整性的可塑性过程。最后，中毒与TCDD的对照成年人没有导致任何异常的眼控制。这些结果表明，AhR的缺乏导致成年人获得性中枢神经系统缺陷。鉴于AhR小鼠和人类婴儿眼球震颤综合征之间的许多共同特征，AhR−/−小鼠可能会深入了解导致先天性眼部疾病的发育机制。
The Aryl hydrocarbon Receptor or AhR, a ligand-activated transcription factor, is known to mediate the toxic and carcinogenic effects of various environmental pollutants such as 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). Recent studies in Caenorhabditis elegans and Drosophila melanogaster show that the orthologs of the AhR are expressed exclusively in certain types of neurons and are implicated in the development and the homeostasis of the central nervous system. While physiological roles of the AhR were demonstrated in the mammalian heart, liver and gametogenesis, its ontogenic expression and putative neural functions remain elusive. Here, we report that the constitutive absence of the AhR in adult mice (AhR−/−) leads to abnormal eye movements in the form of a spontaneous pendular horizontal nystagmus. To determine if the nystagmus is of vestibular, visual, or cerebellar origin, gaze stabilizing reflexes, namely vestibulo-ocular and optokinetic reflexes (VOR and OKR), were investigated. The OKR is less effective in the AhR−/− mice suggesting a deficit in the visuo-motor circuitry, while the VOR is mildly affected. Furthermore, the AhR is expressedin the retinal ganglion cells during the development, however electroretinograms revealed no impairment of retinal cell function. The structure of the cerebellum of the AhR−/− mice is normal which is compatible with the preserved VOR adaptation, a plastic process dependent on cerebellar integrity. Finally, intoxication with TCDD of control adults did not lead to any abnormality of the oculomotor control. These results demonstrate that the absence of the AhR leads to acquired central nervous system deficits in the adults. Given the many common features between both AhR mouse and human infantile nystagmus syndromes, the AhR−/− mice might give insights into the developmental mechanisms which lead to congenital eye disorders.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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DOI：
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发表时间：
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