Dong 2015a

Data type(s)Animal bioassay
Full citationDong YT, Wang Y, Wei N, Zhang QF, Guan ZZ. 2015. Deficit in learning and memory of rats with chronic fluorosis correlates with the decreased expressions of M1 and M3 muscarinic acetylcholine receptors. Arch Toxicol 89: 1981-1991.
AbstractTo 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.
Reference hyperlink
COI reportedAuthors report they have no COI
Funding sourcefinanced by grants from the Natural Science Foundation of China, the Foundation of the Ministry of Science and Technology of China, and the Governmental Foundation at Guizhou Province, China
Study identifier{Dong, 2015 #670}
Author contacted?
Author contact detailsThe author, Z.Z. Guan, at zhizhongguan@yahoo.com was contacted about randomization, allocation concealment, and exposure characterization. No response to the query has been received.
Summary/extraction comments

Tables 2, 4

Originally assessed in the 2016 Fluoride assessment: https://hawcproject.org/assessment/126/

Risk of bias

View details

Loading, please wait... 

Animal bioassay experiments

NameTypeComments
rat F drinking water Subchronic (30-90 days) Animals were divided randomly into two groups of 30 each, i.e., the untreated control group (<0.5 ppm fluoride in drinking water) and the fluoride group (50 ppm fluoride). Each group was fed with normal diet (containing <6 ppm fluoride)…. After 10 months, female adult rats with chronic fluorosis were allowed to become pregnant by natural mating with male adults with chronic fluorosis. After lactation, the offspring rats born from fluorosis rats were fed with the same water containing high fluoride as their parents, and the offspring from untreated control group fed with normal tap water. At the postnatal days 1, 7, 14, 21 and 28, 10 pups in each age group were selected for the experiment.; Sixty one-month-old Sprague–Dawley (SD) rats (half males and half females, and body weight 100–120 g/each) were purchased from the Experimental Animal Center in Guizhou, China, and pre-approved by the regional ethical committee there. The humidity was ranged from 30 to 55 % and temperature remained between 22 and 25 °C. All animals were acclimatized for 1 week in a housing facility before treatment… During the study, the rats were housed in stainless steel cages suspended in stainless steel racks, and the treated water and chow were administered to the animals ad libitum for 10 months.
rat F drinking water Developmental Animals were divided randomly into two groups of 30 each, i.e., the untreated control group (<0.5 ppm fluoride in drinking water) and the fluoride group (50 ppm fluoride). Each group was fed with normal diet (containing <6 ppm fluoride)…. After 10 months, female adult rats with chronic fluorosis were allowed to become pregnant by natural mating with male adults with chronic fluorosis. After lactation, the offspring rats born from fluorosis rats were fed with the same water containing high fluoride as their parents, and the offspring from untreated control group fed with normal tap water. At the postnatal days 1, 7, 14, 21 and 28, 10 pups in each age group were selected for the experiment.; Sixty one-month-old Sprague–Dawley (SD) rats (half males and half females, and body weight 100–120 g/each) were purchased from the Experimental Animal Center in Guizhou, China, and pre-approved by the regional ethical committee there. The humidity was ranged from 30 to 55 % and temperature remained between 22 and 25 °C. All animals were acclimatized for 1 week in a housing facility before treatment… During the study, the rats were housed in stainless steel cages suspended in stainless steel racks, and the treated water and chow were administered to the animals ad libitum for 10 months.