title: Benzyl butyl phthalate exposure impairs learning and memory and attenuates neurotransmission and CREB phosphorylation in mice.
abstract: The existing data are insufficient to evaluate the neurotoxicity of benzyl butyl phthalate (BBP) exposure on the brain, and the underlying mechanisms to explain these effects remain unclear. Kun Ming (KM) mice were exposed to BBP (0, 50, 250, 1250 mg/kg) via gavage for 14 days. Employing the Morris water maze (MWM) test, we observed that mice demonstrated poorer learning and memory performance than the control group at doses of 250 and 1250 mg/kg/day. Reduction of locomotor activity in mice and depression were indicated by a long "dead time" in the Forced Swim Test and tail suspension test. Pathological alterations and oxidative damage to the hippocampus were found. To study the molecular mechanisms underlying BBP toxicity, the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) and pCREB were tested. The modified levels of 5-HT in the hippocampus and the decreased levels of CREB phosphorylation after BBP exposure suggested a potential mechanism underlying BBP toxicity. We hypothesize that BBP exposure causes a decrease in the number of neurotransmitters, which in turn down regulates the levels of CREB phosphorylation by the cAMP/protein kinase A (PKA)-mediated signaling. The results are an attenuation of the effects of CREB downstream, oxidative damage and impaired behavioral performance.
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, China.
authors.forename: Anna
authors.initials: A
authors.lastname: Min
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, China.
authors.forename: Fengming
authors.initials: F
authors.lastname: Liu
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, China. Electronic address: chenmq@mail.ccnu.edu.cn.
authors.forename: Mingqing
authors.initials: M
authors.lastname: Chen
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D051379:Mice; D010766:Phosphorylation; D010795:Phthalic Acids / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D010795:Phthalic Acids; D017382:Reactive Oxygen Species; D012701:Serotonin; D005978:Glutathione; C027561:butylbenzyl phthalate
keywords: Benzyl butyl phthalate (BBP); CREB; Learning and memory; Neurotoxicity; Neurotransmitter