title: Lanthanum enhances glutamate-nitric oxide-3',5'-cyclic guanosine monophosphate pathway in the hippocampus of rats.
abstract: Lanthanum (La) appears to impair learning and memory and increase the toxicity of excitatory amino acids in the central nervous system. The mechanism underlying excitotoxicity induced by La is still unclear. The purpose of this study was to investigate the hippocampal impairment of La exposure and possible mechanism involving the glutamate-nitric oxide (NO)-3'-5'-cyclic guanosine monophosphate (cGMP) pathway. In this study, lactating rats were exposed to 0, 0.25, 0.50, and 1.0% lanthanum chloride (LaCl3) in drinking water, respectively. Their offsprings were exposed to LaCl3 by parental lactation and then administrated with 0, 0.25, 0.50, and 1.0% LaCl3 in drinking water for 1 month. The results showed that La exposure impaired the neuronal ultrastructure and significantly increased the glutamate level, intracellular calcium ion concentrations, and NR1 and NR2B expression in the hippocampi. La exposure significantly enhanced messenger RNA expression and activity levels of inducible NO synthase and increased NO and cGMP levels in the hippocampi in a dose-dependent manner. These results indicate that the mechanism underlying excitotoxicity induced by La is possibly due to alterations of the glutamate-NO-cGMP signaling pathway in the hippocampus. The study provides new findings that may help prevent and improve treatments for La-induced neurotoxicity.
authors.affiliation: Department of Toxicology, School of Public Health, China Medical University, Shenyang, People's Republic of China Shenyang Ninth People's Hospital, Shenyang, People's Republic of China.
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Toxicology, School of Public Health, China Medical University, Shenyang, People's Republic of China Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, People's Republic of China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yang
authors.affiliation: Shenyang Ninth People's Hospital, Shenyang, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
authors.affiliation: Shenyang Ninth People's Hospital, Shenyang, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Toxicology, School of Public Health, China Medical University, Shenyang, People's Republic of China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Medicine, Eastern Liaoning University, Liaoning, People's Republic of China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Toxicology, School of Public Health, China Medical University, Shenyang, People's Republic of China Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, People's Republic of China cmuycai@163.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cai
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006157:Guanosine Monophosphate / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007811:Lanthanum / Q000633:toxicity*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009569:Nitric Oxide; D018698:Glutamic Acid; D007811:Lanthanum; D006157:Guanosine Monophosphate; D002118:Calcium
keywords: Lanthanum; NMDAR; cGMP; glutamate; nitric oxide