PMID- 23736097 OWN - NLM STAT- MEDLINE DCOM- 20140310 LR - 20190504 IS - 1872-7077 (Electronic) IS - 1382-6689 (Linking) VI - 36 IP - 2 DP - 2013 Sep TI - Neurotoxicity of dibutyl phthalate in brain development following perinatal exposure: a study in rats. PG - 392-402 LID - S1382-6689(13)00108-7 [pii] LID - 10.1016/j.etap.2013.05.001 [doi] AB - Dibutyl-phthalate (DBP) is a ubiquitous environmental contaminant. However, its neurotoxic effects on neonatal, immature or mature brains remain unclear. Here, we aimed to investigate the neurotoxicity of perinatal exposure of DBP on rodent offspring animals. Pregnant rats received intragastric DBP (500mg/kg body weight) daily from gestational day (GD) 6 to postnatal day (PND) 21. Animals in the control group received the same volume of edible corn oil. Brain sections or tissues from offspring rats on PND5, PND21 and PND60 were collected for analysis. Histological examination demonstrated that perinatal exposure of DBP resulted in hippocampal neuron loss and structural alternation in neonatal and immature offspring rats (PND5 and PND21), while no significant change was found in mature rats (PND60). DBP exposure induced cell apoptosis in hippocampal neurons of these neonatal and immature animals, as evidenced by the increased number of TUNEL-positive and Annexin V-propidium iodide (PI) positive cells and up-regulated caspase-3 activity. Moreover, DBP exposure decreased the expression of synaptophysin in the hippocampus and reduced both the slope and amplitude of field excitatory postsynaptic potentials (fEPSPs). DBP also impaired the spatial learning and memory of offspring rats. However, no significant difference in the susceptibility to DBP-induced neurotoxicity was found between male and female offspring rats. Our findings indicated that perinatal exposure of DBP could induce neurotoxicity in neonatal and immature offspring animals, but had no influence on mature animals after DBP withdrawal. These results may provide basic experimental evidence for better understanding the neurotoxic effects of DBP on neonatal, immature and mature brains. CI - Copyright (c) 2013 Elsevier B.V. All rights reserved. FAU - Li, Xiu-Juan AU - Li XJ AD - Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, China; Laboratory of Pediatric Neurology, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Jiang, Li AU - Jiang L AD - Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, China; Laboratory of Pediatric Neurology, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. Electronic address: jiangli730412@yahoo.com.cn. FAU - Chen, Long AU - Chen L AD - Laboratory of Pediatric Neurology, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Chen, Heng-Sheng AU - Chen HS AD - Laboratory of Pediatric Neurology, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Li, Xin AU - Li X AD - Laboratory of Pediatric Neurology, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. LA - eng PT - Journal Article DEP - 20130509 PL - Netherlands TA - Environ Toxicol Pharmacol JT - Environmental toxicology and pharmacology JID - 9612020 RN - 0 (Synaptophysin) RN - 0 (Syp protein, rat) RN - 2286E5R2KE (Dibutyl Phthalate) RN - EC 3.4.22.- (Casp3 protein, rat) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Age Factors MH - Animals MH - Apoptosis/*drug effects MH - Behavior, Animal/drug effects MH - Caspase 3/metabolism MH - Dibutyl Phthalate/*toxicity MH - Excitatory Postsynaptic Potentials/drug effects MH - Female MH - Gestational Age MH - Hippocampus/*drug effects/growth & development/metabolism/pathology/physiopathology MH - Male MH - Memory/drug effects MH - Motor Activity/drug effects MH - Neurons/*drug effects/metabolism/pathology MH - Neurotoxicity Syndromes/*etiology/metabolism/pathology/physiopathology/psychology MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - Rats MH - Rats, Sprague-Dawley MH - Synapses/drug effects/metabolism/pathology MH - Synaptophysin/metabolism OTO - NOTNLM OT - DBP OT - Hippocampus OT - Neurotoxicity OT - Perinatal exposure OT - Synapse EDAT- 2013/06/06 06:00 MHDA- 2014/03/13 06:00 CRDT- 2013/06/06 06:00 PHST- 2012/12/21 00:00 [received] PHST- 2013/04/27 00:00 [revised] PHST- 2013/05/02 00:00 [accepted] PHST- 2013/06/06 06:00 [entrez] PHST- 2013/06/06 06:00 [pubmed] PHST- 2014/03/13 06:00 [medline] AID - S1382-6689(13)00108-7 [pii] AID - 10.1016/j.etap.2013.05.001 [doi] PST - ppublish SO - Environ Toxicol Pharmacol. 2013 Sep;36(2):392-402. doi: 10.1016/j.etap.2013.05.001. Epub 2013 May 9.