Prenatal exposure of rats to valproic acid reproduces the cerebellar anomalies associated with autism
Prenatal exposure of rats to valproic acid reproduces the cerebellar anomalies associated with autism
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DOI：
10.1016/s0892-0362(99)00083-5
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发表时间：
2000-05-01
影响因子：
2.9
通讯作者：
Rodier, PM
中科院分区：
文献类型：
--
作者：
Ingram, JL;Peckham, SM;Rodier, PM
解剖结构和颅神经运动核的功能异常已经在一些自闭症患者身上得到证实，并且可以通过在神经管闭合过程中暴露于丙戊酸在大鼠身上进行模拟。据报道，自闭症患者的浦肯野细胞数量和小脑体积，特别是后叶的体积也有所减少。因此，对丙戊酸暴露的大鼠进行了小脑形态学的立体检查。与对照组相比，在胚胎第12.5天暴露于单剂量600 mg/kg丙戊酸钠的大鼠，小脑蚓部的浦肯野细胞明显减少，大脑半球的浦肯野细胞减少幅度不大。细胞数量的减少反映了整个小脑组织体积的减少，而不是细胞密度的减少，细胞密度在所有区域都不受影响。在蚓体内。后叶体积的减少明显大于前叶。研究结果与报道的人类自闭症病例相似。(C) 2000 Elsevier Science Inc.；版权所有。
Abnormalities in anatomy and function of the cranial nerve motor nuclei have been demonstrated in some people with autism and can be modeled in rats by exposure to valproic acid during neural tube closure. Reductions in Purkinje cell number and cerebellar volume, particularly or the posterior lobe, have also been reported in people with autism. Thus, a stereological examination of cerebellar morphology was undertaken in valproate-exposed rats. Compared to controls, rats exposed to a single dose of 600-mg/kg sodium valproate on embryonic day 12.5 had significantly fewer Purkinje cells in the cerebellar vermis and a reduction short of significant in the hemispheres. The diminished cell numbers reflect reductions in tissue volume throughout the cerebellum, rather than cell density, which was unaffected in all regions. Within the vermis. the reduction in volume was significantly greater in the posterior lobe than in the anterior lobe. The results parallel those reported for human cases of autism. (C) 2000 Elsevier Science Inc. All rights reserved.