CHRU de Tours, Tours, France.
Neurosci Lett. 2010 Feb 5;470(1):55-9. doi: 10.1016/j.neulet.2009.12.054. Epub 2009 Dec 28.
In order to explore whether some aspects of the autistic phenotype could be related to impairment of the serotonergic system, we chose an animal model which mimics a potential cause of autism, i.e. rats exposed to valproate (VPA) on the 9th embryonic day (E9). Previous studies have suggested that VPA exposure in rats at E9 caused a dramatic shift in the distribution of serotonergic neurons on postnatal day 50 (PND50). Behavioral studies have also been performed but on rats that were exposed to VPA later (E12.5). Our aim was to test whether VPA exposure at E9 induces comparable behavioral impairments than at E12.5 and causes serotonergic impairments which could be related to behavioral modifications. The results showed significant behavioral impairments such as a lower tendency to initiate social interactions and hyperlocomotor activity in juvenile male rats. The serotonin levels of these animals at PND50 were decreased (-46%) in the hippocampus, a structure involved in social behavior. This study suggests that VPA could have a direct or indirect action on the serotonergic system as early as the progenitor cell stage. Early embryonic exposure to VPA in rats provides a good model for several specific aspects of autism and should help to continue to explore pathophysiological hypotheses.
为了探究自闭症表型的某些方面是否与 5-羟色胺能系统的损伤有关，我们选择了一种动物模型，该模型模拟了自闭症的一个潜在病因，即在第 9 天胚胎期（E9）对大鼠暴露于丙戊酸（VPA）。先前的研究表明，在 E9 时对大鼠暴露于 VPA 会导致 50 日龄（PND50）时 5-羟色胺能神经元的分布发生显著变化。也已经进行了行为研究，但研究对象是在 E12.5 时暴露于 VPA 的大鼠。我们的目的是测试在 E9 时暴露于 VPA 是否会引起与在 E12.5 时暴露于 VPA 相似的行为损伤，并导致与行为改变相关的 5-羟色胺能损伤。结果显示，幼年雄性大鼠表现出明显的行为损伤，如社交互动的倾向较低和运动过度。这些动物在 PND50 时的 5-羟色胺水平在海马体中下降（-46%），海马体是参与社交行为的结构。这项研究表明，VPA 早在祖细胞阶段就可能对 5-羟色胺能系统产生直接或间接的作用。大鼠胚胎早期暴露于 VPA 为自闭症的几个特定方面提供了一个很好的模型，应该有助于继续探索病理生理学假说。
