Effects of chronic fluoride exposure on spatial learning and memory and hippocampal PI3K/Akt/mTOR signaling pathway in second offspring rats
10.3760/cma.j.cn231583-20221229-00416
- VernacularTitle:慢性氟暴露对子二代大鼠空间学习记忆能力和海马PI3K/Akt/mTOR信号通路的影响
- Author:
Chenfei ZHAO
1
;
Li AN
;
Yu GE
;
Chun XIE
Author Information
1. 贵州医科大学公共卫生与健康学院 环境污染与疾病监控教育部重点实验室，贵阳 550025
- Keywords:
Fluorine;
Hippocampus;
Learning and memory;
Phosphatidylinositol 3-kinase;
Protein kinase B;
Mammalian target of rapamycin
- From:
Chinese Journal of Endemiology
2023;42(11):861-867
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the effects of chronic fluoride exposure on spatial learning and memory and the expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR) in hippocampus of second offspring (F2 generation) rats.Methods:Sixteen clean-grade healthy SD pregnant rats were randomly divided into four groups according to their body mass [(200 ± 50) g] using a random number table method: the control group [0 mg/L sodium fluoride (NaF)], and the low, medium, and high fluoride groups (60, 120, 240 mg/L NaF), with four rats in each group. Fluoride exposure was carried out from the 0th day of pregnancy to the 21st day of birth (PND21) of first offspring (F1 generation) rats through free drinking water. The F1 generation rats continued to be exposed to fluoride at the same dose and method as the female rats in the same group until the 90th day of birth (PND90). Six rats (male to female ratio 2∶1) were selected from each group and housed together. Female F1 were continuously exposed with the same method until PND21 of the F2 generation rats. Eight F2 generation rats (4 males and 4 females, with a male to female ratio of 1∶1 in the same litter) were randomly selected from each group and exposed to NaF with corresponding concentrations from PND22 to PND90. Before the execution of F2 generation rats, Morris water maze experiment was used to examine spatial learning and memory ability. After execution, real-time fluorescence quantitative PCR (qRT-PCR) and Western blotting were used to detect the mRNA and protein expression levels of PI3K, Akt, and mTOR in the hippocampus, respectively.Results:Compared with the control group days 2 - 4 [(46.72 ± 4.24), (24.87 ± 3.15), (14.10 ± 2.52) s], the escape latency of F2 generation rats was prolonged in the medium and high fluoride groups on the second day [(53.96 ± 3.45), (54.48 ± 6.20) s] and on the fourth day [(19.47 ± 2.51), (25.02 ± 3.86) s], and in the low, medium and high fluoride groups on the third day [(32.37 ± 4.56), (37.32 ± 4.65), (41.79 ± 7.08) s, P < 0.05]. Compared with the control group, the first arrival time of F2 generation rats in the high fluoride group was prolonged, while the number of crossing platforms in both the medium and high fluoride groups decreased ( P < 0.05). Except for mTOR mRNA in the low fluoride group, the mRNA and protein expression levels of PI3K, Akt, mTOR in the hippocampus of rats in all other exposure groups were lower than those in the control group ( P < 0.05). The results of correlation analysis showed that NaF concentration was positively correlated with the escape latency and the first arrival time of F2 generation rats on days 1 - 4 ( r = 0.44, 0.57, 0.79, 0.80, 0.58, P < 0.05), and negatively correlated with the mRNA and protein expression levels of PI3K, Akt, mTOR in the hippocampus of F2 generation rats, as well as the number of crossing platforms ( r = - 0.71, - 0.67, - 0.73, - 0.61, - 0.58, - 0.71, - 0.82, P < 0.05). Conclusion:Chronic fluoride exposure can lead to spatial learning and memory impairment in F2 generation rats, and its mechanism of action may be related to the inhibition of the PI3K/Akt/mTOR signaling pathway in the hippocampus.
