Ramos Raddy L, Van Dine Sarah E, Gilbert Mary E, Leheste Joerg R, Torres German
Department of Biomedical Sciences, College of Osteopathic Medicine, New York Institute of Technology, Northern Boulevard, PO Box 8000, Old Westbury, NY, 11568, USA.
Toxicity Assessment Division, Neurotoxicology Branch, US Environmental Protection Agency, Research Triangle Park, Durham, NC, USA.
Cerebellum. 2015 Dec;14(6):624-31. doi: 10.1007/s12311-015-0657-9.
The cerebellar vermis is particularly vulnerable to neurodevelopmental malformations in humans and rodents. Sprague-Dawley, and Long-Evans rats exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the vermis. Malformations are almost exclusively found along the primary fissure and are indicative of deficits of neuronal migration during cerebellar development. In the present report, we test the prediction that genetically engineered rats on Sprague-Dawley or Long-Evans backgrounds will also exhibit the same cerebellar malformations. Consistent with our hypothesis, we found that three different transgenic lines on two different backgrounds had cerebellar malformations. Heterotopia in transgenic rats had identical cytoarchitecture as that observed in wild-type rats including altered morphology of Bergmann glia. In light of the possibility that heterotopia could affect results from behavioral studies, these data suggest that histological analyses be performed in studies of cerebellar function or development when using genetically engineered rats on these backgrounds in order to have more careful interpretation of experimental findings.
小脑蚓部在人类和啮齿动物中特别容易出现神经发育畸形。斯普拉格-道利大鼠和长-伊文斯大鼠表现出自发性小脑畸形，由蚓部分子层中的异位神经元和神经胶质组成。畸形几乎只在初级裂沟沿线发现，这表明小脑发育过程中神经元迁移存在缺陷。在本报告中，我们检验了这样的预测：在斯普拉格-道利或长-伊文斯背景下的基因工程大鼠也会表现出相同的小脑畸形。与我们的假设一致，我们发现两种不同背景下的三个不同转基因品系都有小脑畸形。转基因大鼠中的异位组织具有与野生型大鼠中观察到的相同细胞结构，包括伯格曼神经胶质细胞形态的改变。鉴于异位可能影响行为学研究结果，这些数据表明，在使用这些背景下的基因工程大鼠进行小脑功能或发育研究时，应进行组织学分析，以便更谨慎地解释实验结果。
