title: Deficit in learning and memory of rats with chronic fluorosis correlates with the decreased expressions of M1 and M3 muscarinic acetylcholine receptors.
abstract: To reveal the molecular mechanism of deficit in learning and memory induced by chronic fluorosis, the expression of muscarinic acetylcholine receptors (mAChRs) and oxidative stress were investigated. Sixty Sprague-Dawley (SD) rats were divided randomly into two groups (30 cases in each), i.e., the control group (<0.5 ppm fluoride in drinking water) and the fluoride group (50 ppm fluoride) for 10 months of treatment. The pups born from SD mothers with or without chronic fluorosis were selected at postnatal days 1, 7, 14, 21 and 28 for experiments (10 for each age). Spatial learning and memory were evaluated by Morris water maze test. The expressions of M1 and M3 mAChRs at the protein and mRNA levels were determined by Western blotting and real-time PCR, respectively. In addition, the contents of (·)OH, H2O2, O2(·-) and malondialdehyde (MDA), and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in brains were quantitated by biochemical methods. Our results showed that as compared to controls, the abilities of learning and memory were declined in the adult rats and the offspring rats of postnatal day 28 in the fluoride groups; the expressions of both M1 and M3 mAChRs were significantly reduced at protein and mRNA levels; and the levels of (·)OH, H2O2, O2(·-) and MDA were significantly increased, while the activities of SOD and GSH-Px decreased. Interestingly, the decreased protein levels of M1 and M3 mAChRs were significantly correlated with the deficits of learning and memory and high level of oxidative stress induced by chronic fluorosis. Our results suggest that the mechanism for the deficits in learning and memory of rats with chronic fluorosis may be associated with the decreased expressions of M1 and M3 in mAChRs, in which the changes in the receptors might be the result of the high level of oxidative stress occurring in the disease.
authors.affiliation: Department of Pathology in the Affiliated Hospital, Guiyang Medical University, Guiyang, 550004, People's Republic of China.
authors.forename: Yang-Ting
authors.initials: YT
authors.lastname: Dong
authors.affiliation: Department of Pathology in the Affiliated Hospital, Guiyang Medical University, Guiyang, 550004, People's Republic of China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology in the Affiliated Hospital, Guiyang Medical University, Guiyang, 550004, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Wei
authors.affiliation: Key Laboratory of Molecular Biology, Guiyang Medical University, Guiyang, 550004, People's Republic of China.
authors.forename: Qi-Fang
authors.initials: QF
authors.lastname: Zhang
authors.affiliation: Department of Pathology in the Affiliated Hospital, Guiyang Medical University, Guiyang, 550004, People's Republic of China. guan169713@qq.com.|Key Laboratory of Molecular Biology, Guiyang Medical University, Guiyang, 550004, People's Republic of China. guan169713@qq.com.
authors.forename: Zhi-Zhong
authors.initials: ZZ
authors.lastname: Guan
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D009050:Fluorosis, Dental / Q000150:complications*; D005786:Gene Expression Regulation; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning; D008569:Memory Disorders / Q000209:etiology*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043643:Receptor, Muscarinic M1 / Q000235:genetics*; D043587:Receptor, Muscarinic M3 / Q000235:genetics*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
keywords: Chronic fluorosis; Learning and memory; Oxidative stress; Rat brains; mAChRs