| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2786008 | International Journal of Developmental Neuroscience | 2013 | 7 Pages |
In utero exposure to valproic acid (VPA) may cause symptoms related to autism spectrum disorder (ASD). An abnormal serotonergic (5-HT) system has been implicated in the etiology of ASD. In the present study, we have examined the expression and distribution of two early inducers of 5-HT neurons in rat embryos, to elucidate the prenatal development of 5-HT neurons after VPA exposure at embryonic day (E) 9.5. Whole-embryo in situ hybridization at E11.5 showed that the expression of sonic hedgehog, one of the early inducers of 5-HT neurons, was reduced around the isthmus in the VPA-exposed group. Furthermore, whole-mount immunohistochemistry of the hindbrain and quantitative analysis of 5-HT neurons in the rostral raphe nucleus (rRN) revealed that neuronal distribution in the caudal part of the rRN was narrower at E15.5 in the VPA-exposed group than in controls. Thus, the early development of 5-HT neurons was altered after VPA exposure in utero. The observed prenatal alteration may be significant in the etiology of autism.
► We examined 5-HT neurons in a model of autism based on prenatal VPA exposure. ► Prenatal VPA exposure attenuated the expression of Shh at E11.5. ► The distribution of 5-HT neurons at E15.5 was altered. ► The expansion of caudal 5-HT neurons was suppressed. ► These prenatal alterations might contribute to the etiology of autism.
