title: Fluoride and arsenic exposure affects spatial memory and activates the ERK/CREB signaling pathway in offspring rats.
abstract: Fluoride and arsenic are inorganic contaminants that occur in the natural environment. Chronic fluoride and/or arsenic exposure can induce developmental neurotoxicity and negatively influence intelligence in children, although the underlying molecular mechanisms are poorly understood. This study explored the effects of fluoride and arsenic exposure in drinking water on spatial learning, memory and key protein expression in the ERK/CREB signaling pathway in hippocampal and cerebral cortex tissue in rat offspring. Pregnant rats were divided into four groups. Control rats drank tap water, while rats in the three exposure groups drank water with sodium fluoride (100mg/L), sodium arsenite (75mg/L), and a sodium fluoride (100mg/L) and sodium arsenite (75mg/L) combination during gestation and lactation. After weaning, rat pups drank the same solution as their mothers. Spatial learning and memory ability of pups at postnatal day 21 (PND21) and postnatal day 42 (PND42) were measured using a Morris water maze. ERK, phospho-ERK (p-ERK), CREB and phospho-CREB (p-CREB) protein expression in the hippocampus and cerebral cortex was detected using Western blot. Compared with the control pups, escape latencies increased in PND42 pups exposed to arsenic and co-exposed to fluoride and arsenic, and the short-term and long-term spatial memory ability declined in pups exposed to fluoride and arsenic, both alone and in combination. Compared with controls, ERK and p-ERK levels decreased in the hippocampus and cerebral cortex in pups exposed to combined fluoride and arsenic. CREB protein expression in the cerebral cortex decreased in pups exposed to fluoride, arsenic, and the fluoride and arsenic combination. p-CREB protein expression in both the hippocampus and cerebral cortex was decreased in pups exposed to fluoride and arsenic in combination compared to the control group. There were negative correlation between the proteins expression and escape latency periods in pups. These data indicate that exposure to fluoride and arsenic in early life stage changes ERK, p-ERK, CREB and p-CREB protein expression in the hippocampus and cerebral cortex of rat offspring at PND21 and PND 42, which may contribute to impaired neurodevelopment following exposure.
authors.affiliation: Department of Occupational and Environmental Health, Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, Tangshan, Hebei, PR China.
authors.forename: Yu-Peng
authors.initials: YP
authors.lastname: Zhu
authors.affiliation: Department of Occupational and Environmental Health, Liaoning Provincial Key Lab of Arsenic Biological Effect and Poisoning, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Xi
authors.affiliation: Department of Occupational and Environmental Health, Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, Tangshan, Hebei, PR China.
authors.forename: Ming-Yan
authors.initials: MY
authors.lastname: Li
authors.affiliation: Department of Occupational and Environmental Health, Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, Tangshan, Hebei, PR China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Ding
authors.affiliation: Department of Occupational and Environmental Health, Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, Tangshan, Hebei, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.affiliation: Laboratory Animal Center, North China University of Science and Technology, Tangshan, Hebei, PR China.
authors.forename: Fu-Yuan
authors.initials: FY
authors.lastname: Cao
authors.affiliation: Department of Occupational and Environmental Health, Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, Tangshan, Hebei, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Occupational and Environmental Health, Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, Tangshan, Hebei, PR China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Liu
authors.affiliation: Department of Occupational and Environmental Health, Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, Tangshan, Hebei, PR China.
authors.forename: Jun-Wang
authors.initials: JW
authors.lastname: Tong
authors.affiliation: Department of Occupational and Environmental Health, Hebei Province Key Laboratory of Occupational Health and Safety for Coal Industry, School of Public Health, North China University of Science and Technology, Tangshan, Hebei, PR China. Electronic address: jiangshoufang@163.com.
authors.forename: Shou-Fang
authors.initials: SF
authors.lastname: Jiang
mesh_terms: D000367:Age Factors; D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002327:Cariostatic Agents / Q000633:toxicity*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005260:Female; D005459:Fluorides / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced*; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects
chemical_list: D002327:Cariostatic Agents; D017362:Cyclic AMP Response Element-Binding Protein; D001151:Arsenic; D005459:Fluorides
keywords: Arsenic; CREB; ERK; Fluoride; Learning and memory