Yanhui Gao

Sodium Arsenite-Induced Learning and Memory Impairment Is Associated with Endoplasmic Reticulum Stress-Mediated Apoptosis in Rat Hippocampus

Chronic arsenic exposure has been associated to cognitive deficits. However, mechanisms remain unknown. The present study investigated the neurotoxic effects of sodium arsenite in drinking water over different dosages and time periods. Based on results from the Morris water maze (MWM) and morphological analysis, an exposure to sodium arsenite could induce neuronal damage in the hippocampus, reduce learning ability, and accelerate memory impairment. Sodium arsenite significantly increased homocysteine levels in serum and brain. Moreover, sodium arsenite triggered unfolded protein response (UPR), leading to the phosphorylation of RNA-regulated protein kinase-like ER kinase (PERK) and eukaryotic translation initiation factor 2 subunit α (eIF2α), and the induction of activating transcription factor 4 (ATF4). Arsenite exposure also stimulated the expression of the endoplasmic reticulum (ER) stress markers, glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and the cleavage of caspase-12. Furthermore, exposure to arsenite enhanced apoptosis as demonstrated by expression of caspase-3 and TUNEL assay in the hippocampus. The results suggest that exposure to arsenite can significantly decrease learning ability and accelerate memory impairment. Potential mechanisms are related to enhancement of homocysteine and ER stress-induced apoptosis in the hippocampus.

Association between vitamin D receptor gene FokI polymorphism and skeletal fluorosis of the brick-tea type fluorosis: a cross sectional, case control study

Background Brick-tea type fluorosis is a public health concern in the north west area of China. The vitamin D receptor (VDR)-FokI polymorphism is considered to be a regulator of bone metabolism and calcium resorption. However, the association of VDR-FokI polymorphism with the risk of brick-tea type fluorosis has not been reported. Materials and methods A cross sectional, case control study was conducted in three provinces (Inner Mongolia, Qinghai and Sinkiang) in China. The fluoride content of Brick-tea water and urine was tested using the standards GB 1996–2005 and WS/T89-2006 (China), respectively. Skeletal fluorosis was diagnosed using the standard WS/192-2008 (China). The VDR-FokI polymorphism was detected by the Sequenom MassARRAY system. Result Compared with carriers of the CC genotype, participants with the CT/TT genotype had a significantly decreased risk of skeletal fluorosis (OR=0.761 (95% CI 0.580 to 0.997)), after adjustment for risk factors. When investigated among ethnic groups, the protective effect of the CT/TT genotype was limited in the Mongolian participants (OR=0.525 (95% CI 0.278 to 0.991)). Moreover, the interaction of VDR-FokI with risk factors was only found in Mongolian participants: the protective effect of the CT/TT genotype was limited to participants with >7.0 mg/day daily intake of tea fluoride (OR=0.085 (95% CI 0.009 to 0.851), participants with >3.2 mg/L urine fluoride (OR=0.103 (95% CI 0.017 to 0.633)) or participants aged 46–65 years (OR=0.404 (95% CI 0.177 to 0.922). Conclusions Our data suggest that the CT/TT genotype of VDR-FokI may be a protective factor for brick-tea type skeletal fluorosis, and this effect is pronounced in Mongolian participants.

Pathological changes and effect on the learning and memory ability in rats exposed to fluoride and aluminum

Background: The aim of this study is to establish a single and combined intoxication model of fluoride and aluminum so as to observe the impact of these chemicals on the learning and memory ability and the pathologic changes in the brains of rats. Methods: Forty male Wistar rats were randomly assigned into control (distilled water), fluoride (50 mg L−1 F−), aluminum (100 mg L−1 Al3+) and combined groups (50 mg L−1 F− and 100 mg L−1 Al3+). The experiment lasted for 3 months. The short-term memory ability and learning and memory ability of the rats were assessed using Y maze and Morris water maze, respectively. At the same time, the concentrations of fluoride and aluminum in urine and brain were measured. The pathologic and microstructural changes in the hippocampus were observed via optical microscopy and transmission electron microscopy, and the expression of the Aβ1–42 protein was detected using immunohistochemistry. Results: The results showed that the learning and memory ability of each toxicant-exposed group was decreased; the most severe was in the aluminum group, followed by the combined group, and the lightest was in the fluoride group. Although there was no significant difference between all the groups, both fluoride and aluminum could lower the short-term memory ability of the rats. In addition, different pathologic and microstructural changes were observed in fluoride, aluminum and combined groups. Compared with the control group, the expression of Aβ1–42 protein in the aluminum group was highest, followed by the combined group, and that in the fluoride group was lowest. Conclusions: In conclusion, combined intake of fluoride and aluminum may alleviate the deficits to learning and memory ability caused by aluminum intoxication.