PMID- 25291237 OWN - NLM STAT- MEDLINE DCOM- 20150821 LR - 20200106 IS - 1873-474X (Electronic) IS - 0736-5748 (Linking) VI - 38 DP - 2014 Nov TI - Prenatal sodium arsenite affects early development of serotonergic neurons in the fetal rat brain. PG - 204-12 LID - S0736-5748(14)00165-8 [pii] LID - 10.1016/j.ijdevneu.2014.09.005 [doi] AB - Prenatal arsenite exposure has been associated with developmental disorders in children, including reduced IQ and language abnormalities. Animal experiments have also shown that exposure to arsenite during development induced developmental neurotoxicity after birth. However, the evidence is not enough, and the mechanism is poorly understood, especially on the exposure during early brain development. This study assessed effects of sodium (meta) arsenite shortly after exposure on early developing fetal rat brains. Pregnant rats were administered 50 mg/L arsenite in their drinking water or 20 mg/kg arsenite orally using a gastric tube, on gestational days (GD) 9-15. Fetal brains were examined on GD16. Pregnant rats administered 20 mg/kg arsenite showed reductions in maternal body weight gain and food consumption during treatment, but not with 50 mg/L arsenite. Arsenite did not affect fetal development, as determined by body weight, mortality and brain size. Arsenite also did not induce excessive cell death or affect neural cell division in any region of the fetal neuroepithelium. Thyrosine hydroxylase immunohistochemistry revealed no difference in the distribution of catecholaminergic neurons between fetuses of arsenite treated and control rats. However, reductions in the number of serotonin positive cells in the fetal median and dorsal raphe nuclei were observed following maternal treatment with 20mg/kg arsenite. Image analysis showed that the serotonin positive areas decreased in all fetal mid- and hind-brain areas without altering distribution patterns. Maternal stress induced by arsenite toxicity did not alter fetal development. These results suggest that arsenite-induced neurodevelopmental toxicity involves defects in the early development of the serotonin nervous system. CI - Copyright (c) 2014 ISDN. Published by Elsevier Ltd. All rights reserved. FAU - Senuma, Mika AU - Senuma M AD - Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano, Kanagawa 257-8523, Japan. Electronic address: senuma.m@fdsc.or.jp. FAU - Mori, Chisato AU - Mori C AD - Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City 260-8670, Japan. Electronic address: cmori@faculty.chiba-u.jp. FAU - Ogawa, Tetsuo AU - Ogawa T AD - Department of Biology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan. Electronic address: ogawatetsuo@hotmail.co.jp. FAU - Kuwagata, Makiko AU - Kuwagata M AD - Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano, Kanagawa 257-8523, Japan. Electronic address: kuwagata.m@fdsc.or.jp. LA - eng PT - Journal Article DEP - 20141005 PL - United States TA - Int J Dev Neurosci JT - International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience JID - 8401784 RN - 0 (Arsenates) RN - 333DO1RDJY (Serotonin) RN - 7XO134LHLN (sodium arsenate) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) SB - IM MH - Age Factors MH - Animals MH - Animals, Newborn MH - Arsenates/*toxicity MH - Body Weight/drug effects MH - Brain/embryology/*pathology MH - Cell Proliferation/drug effects MH - Developmental Disabilities/*etiology MH - Dose-Response Relationship, Drug MH - Embryo, Mammalian MH - Female MH - Male MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*pathology/*physiopathology MH - Rats MH - Rats, Sprague-Dawley MH - Serotonergic Neurons/*pathology MH - Serotonin/metabolism MH - Tyrosine 3-Monooxygenase/metabolism OTO - NOTNLM OT - Developmental neurotoxicity OT - Fetal brain OT - Immunohistochemistry OT - Rat OT - Serotonin OT - Sodium arsenite EDAT- 2014/10/08 06:00 MHDA- 2015/08/22 06:00 CRDT- 2014/10/08 06:00 PHST- 2014/08/10 00:00 [received] PHST- 2014/09/26 00:00 [revised] PHST- 2014/09/26 00:00 [accepted] PHST- 2014/10/08 06:00 [entrez] PHST- 2014/10/08 06:00 [pubmed] PHST- 2015/08/22 06:00 [medline] AID - S0736-5748(14)00165-8 [pii] AID - 10.1016/j.ijdevneu.2014.09.005 [doi] PST - ppublish SO - Int J Dev Neurosci. 2014 Nov;38:204-12. doi: 10.1016/j.ijdevneu.2014.09.005. Epub 2014 Oct 5.