title: Effects of lead exposure on D-serine metabolism in the hippocampus of mice at the early developmental stages.
abstract: The aim of this study was to explore the mechanisms of lead neurotoxicity by focusing on the alteration of D-serine metabolism in the hippocampus of mice at the early life. Mother mice and their offspring were exposed to 0, 0.5, 1.0 and 2.0 g/L lead in lead acetate via drinking water from the first day of gestation until the postnatal day (PND) 40. Morris water maze was used to measure the spatial learning and memory ability of PND 40 mice. Expressions of serine racemase (SR), D-amino acid oxidase (DAAO), alanine-serine- cysteine transporter-1 (asc-1) and subunits of N-methyl-D-aspartate receptor (NMDAR) in the hippocampus of PND 10, 20 and 40 mice were examined by western blot and real time RT-PCR. Findings from this study disclosed that the spatial learning ability of mice tested by place trial could be significantly impaired by 0.5 g/L lead exposure, and the spatial memory ability tested by probe trail could be impaired by 1.0 g/L lead exposure. Exposure to 2.0 g/L lead in the water could significantly inhibit the protein and mRNA expression of SR; conversely enhance the expression of DAAO protein and mRNA in the hippocampus during the early developmental stages. However, the protein expressions of DAAO and asc-1 in the hippocampus were significantly enhanced by 0.5 g/L lead exposure at different developmental stages. On the other hand, the protein and mRNA expressions of both NR1 and NR2A were inhibited significantly by 1.0 g/L lead exposure since PND 10, and by 0.5 g/L lead exposure since PND 20. Noteworthy, the protein expression of NR2B was inhibited significantly by 0.5 g/L lead exposure in PND 10 mice, and by 1.0 g/L lead exposure in PND 20 mice, but there was no significant group difference in PND 40 mice. Meanwhile, expressions of asc-1 and NR2B mRNA were not affected obviously by lead exposure. In conclusion, chronic lead exposure during brain development might affect D-serine metabolism by enhancing its degradation, which might be related to the inhibited expression of NMDAR subunits, and furthermore contribute to deficits in learning and memory ability in mice.
authors.affiliation: Department of Environmental and Occupational Health, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Environmental and Occupational Health, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Environmental and Occupational Health, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Physiology, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Environmental and Occupational Health, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Gaoyang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Environmental and Occupational Health, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Lanyue
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Environmental and Occupational Health, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Fenghong
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Environmental and Occupational Health, School of Public Health, China Medical University, Shenyang, Liaoning, PR China. Electronic address: jinyp@mail.cmu.edu.cn.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000367:Age Factors; D027182:Amino Acid Transport System y+ / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003605:D-Amino-Acid Oxidase / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D020264:Lead Poisoning, Nervous System, Childhood / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008568:Memory / Q000187:drug effects; D051379:Mice; D009942:Organometallic Compounds / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D019998:Racemases and Epimerases / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D065853:Spatial Learning / Q000187:drug effects; D000099300:Serine Racemase
chemical_list: D027182:Amino Acid Transport System y+; D003605:D-Amino-Acid Oxidase; D009942:Organometallic Compounds; D012333:RNA, Messenger; D019998:Racemases and Epimerases; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D000099300:Serine Racemase; C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C412624:Slc7a10 protein, mouse; C485958:Dao1 protein, mouse; C008261:lead acetate
keywords: Ability of learning and memory; Lead exposure; Mice; Subunits of N-methyl-d-aspartate receptor; d-serine metabolism