Hamot Medical Center, Department of Neurology, USA.
Brain Res. 2011 Jun 29;1398:102-12. doi: 10.1016/j.brainres.2011.05.013. Epub 2011 May 13.
Autism is a neurodevelopmental disorder characterized by social difficulties, impaired communication skills and repetitive behavioral patterns. Additionally, there is evidence that auditory deficits are a common feature of the autism spectrum disorders. Despite the prevalence of autism, the neurobiology of this disorder is poorly understood. However, abnormalities in neuronal morphology, cell number and connectivity have been described throughout the autistic brain. Indeed, we have demonstrated significant dysmorphology in the superior olivary complex (SOC), a collection of auditory brainstem nuclei, in the autistic brain. Prenatal exposure to valproic acid (VPA) in humans has been associated with autism and in rodents prenatal VPA exposure produces many neuroanatomical and behavioral deficits associated with autism. Thus, in an effort to devise an animal model of the autistic auditory brainstem, we have investigated neuronal number and morphology in animals prenatally exposed to valproic acid (VPA). In VPA exposed rats, we find significantly fewer neurons and significant alterations in neuronal morphology. Thus, prenatal VPA exposure in rats appears to produce similar dysmorphology as we have reported in the autistic human brain.
自闭症是一种神经发育障碍，其特征是社交困难、沟通技巧受损和重复行为模式。此外，有证据表明，听觉缺陷是自闭症谱系障碍的一个常见特征。尽管自闭症的发病率很高，但这种疾病的神经生物学机制仍不清楚。然而，已经在自闭症大脑中描述了神经元形态、细胞数量和连接的异常。事实上，我们已经证明了在听觉脑干核团的上橄榄复合体（SOC）中存在显著的畸形，在自闭症大脑中也是如此。人类在产前接触丙戊酸（VPA）与自闭症有关，而在啮齿动物中，产前 VPA 暴露会产生许多与自闭症相关的神经解剖和行为缺陷。因此，为了设计自闭症听觉脑干的动物模型，我们研究了产前暴露于丙戊酸（VPA）的动物中的神经元数量和形态。在 VPA 暴露的大鼠中，我们发现神经元数量明显减少，并且神经元形态发生了显著改变。因此，大鼠产前 VPA 暴露似乎会产生与我们在自闭症人类大脑中报告的相似的畸形。
