title: Neurotoxicity of dibutyl phthalate in brain development following perinatal exposure: a study in rats.
abstract: 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.
authors.affiliation: 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.
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: 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.
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Heng-Sheng
authors.initials: HS
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
mesh_terms: D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D003993:Dibutyl Phthalate / Q000633:toxicity*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D016708:Synaptophysin; C569016:Syp protein, rat; D003993:Dibutyl Phthalate; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: DBP; Hippocampus; Neurotoxicity; Perinatal exposure; Synapse