title: The effects of prenatal exposure to valproic acid on the initial development of serotonergic neurons.
abstract: 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.
authors: Department of Developmental and Regenerative Medicine, Mie University Graduate School of Medicine, Japan.
authors: Akiko
authors: A
authors: Oyabu
authors: Masaaki
authors: M
authors: Narita
authors: Yasura
authors: Y
authors: Tashiro
mesh_terms: D000818:Animals; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D059326:Serotonergic Neurons / Q000187:drug effects* / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D053823:Hedgehog Proteins; D014635:Valproic Acid