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The effects of prenatal exposure to valproic acid on the initial development of serotonergic neurons
Author(s) -
Oyabu Akiko,
Narita Masaaki,
Tashiro Yasura
Publication year - 2013
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2013.01.006
Subject(s) - serotonergic , valproic acid , in utero , in situ hybridization , biology , raphe , dorsal raphe nucleus , sonic hedgehog , hindbrain , embryo , hedgehog , endocrinology , prenatal development , medicine , neural development , neuroscience , serotonin , fetus , central nervous system , microbiology and biotechnology , epilepsy , pregnancy , signal transduction , receptor , gene expression , genetics , gene
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.