title: Epigenetic histone modification regulates developmental lead exposure induced hyperactivity in rats.
abstract: Lead (Pb) exposure was commonly considered as a high environmental risk factor for the development of attention-deficit/hyperactivity disorder (ADHD). However, the molecular basis of this pathological process still remains elusive. In light of the role of epigenetics in modulating the neurological disease and the causative environment, the alterations of histone modifications in the hippocampus of rats exposed by various doses of lead, along with concomitant behavioral deficits, were investigated in this study. According to the free and forced open field test, there showed that in a dosage-dependent manner, lead exposure could result in the increased locomotor activity of rats, that is, hyperactivity: a subtype of ADHD. Western blotting assays revealed that the levels of histone acetylation increased significantly in the hippocampus by chronic lead exposure, while no dramatic changes were detected in terms of expression yields of ADHD-related dopaminergic proteins, indicating that histone acetylation plays essential roles in this toxicant-involved pathogenesis. In addition, the increased level of histone acetylation might be attributed to the enzymatic activity of p300, a typical histone acetyltransferase, as the transcriptional level of p300 was significantly increased upon higher-dose Pb exposure. In summary, this study first discovered the epigenetic mechanism bridging the environmental influence (Pb) and the disease itself (ADHD) in the histone modification level, paving the way for the comprehensive understanding of ADHD's etiology and in further steps, establishing the therapy strategy of this widespread neurological disorder.
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui 230009, PR China.
authors.forename: Man
authors.initials: M
authors.lastname: Luo
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui 230009, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui 230009, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Cai
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui 230009, PR China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Tang
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui 230009, PR China.
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Ge
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui 230009, PR China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Liu
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui 230009, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui 230009, PR China.
authors.forename: Fan
authors.initials: F
authors.lastname: Hu
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui 230009, PR China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, PR China.
authors.forename: Di-Yun
authors.initials: DY
authors.lastname: Ruan
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, Anhui 230009, PR China. Electronic address: wanghl@hfut.edu.cn.
authors.forename: Hui-Li
authors.initials: HL
authors.lastname: Wang
mesh_terms: D000107:Acetylation; D000367:Age Factors; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D059647:Gene-Environment Interaction; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006657:Histones / Q000378:metabolism*; D006948:Hyperkinesis / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D020264:Lead Poisoning, Nervous System, Childhood / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D008297:Male; D018811:Maternal Exposure; D009043:Motor Activity / Q000187:drug effects*; D009942:Organometallic Compounds / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050638:Receptors, Dopamine D4 / Q000187:drug effects / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D006657:Histones; D009942:Organometallic Compounds; D012333:RNA, Messenger; D050638:Receptors, Dopamine D4; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C493601:Drd4 protein, rat; C493216:Slc6a3 protein, rat; C008261:lead acetate
keywords: Epigenetic; Histone acetylation; Hyperactivity; Lead (Pb)