Changes of the c-Jun N-terminal Idnase in the brains of rats with chronicfluorosis

Abstract

Objective To investigate the expression of c-Jun-N-terminal kinase（JNK） in rat brains with chronic fluorosis and try to reveal the molecular mechanism for the neural impairment induced by the disease.Methods The rats were randomly divided into 3 groups, normal control group（drinking water containing less than 0.5 mg/L of sodium fluoride, NaF）, lower fluoride exposed group（drinking water containing 5 mg/L NaF） and higher fluoride exposed group（drinking water containing 50 mg/L NaF）, 24 in every group. The rats were examined at the sixth month after feeding. The concentration of fluorine in urine and blood was detected by F-ion selective electrode. The expression of JNK in brains was investigated by using Western blotting and immunohitochemistry staining, and analyze the correlation between activating of JNK and the concentration of fluorine in blood. Results The increased concentration of fluorine in urine（control： 0.92 ± 0.30, lower fluoride exposed group： 2.56 ± 0.91,higher fluoride exposed group： 5.73 ± 3.14, P 〈 0.05） were observed when 6 months after the beginning of the experiment, and the amount of fluorine in blood was also higher in rats with fluorosis（control： 0.12 ± 0.07, lower fluoride exposed group： 0.36 ± 0.14, higher fluoride exposed group： 0.50 ± 0.18, P 〈 0.05）. The expression of phospho-JNK at protein levels were higher in the brains of rats with fluorosis than that of controls （control： 1.00 ± 0.37, lower fluoride exposed group： 1.20 ± 0.28, higher fluoride exposed group： 1.74 ± 0.69, P 〈 0.05）, whereas no change of total-JNK was found（F = 0.046, P 〉 0.05）. Furthermore, the expression of phospho-JNK in the parietal cortex（119.3 ± 14.1）, occipital cortex（112.7 ± 5.4）, hippocampus CA3（100.6 ± 8.9）, dorsal thalamus （117.8 ± 10.4） and olivary nucleus（ 112.6 ± 5.9） of rats in higher fluoride exposed group were higher than that in control（ 104.1 ± 8.9,106.6 ± 9.6,106.6 ± 9.7,108.9 ± 6.4,100.3 ± 8.4, all P 〈 0.05） and lower fluoride exposed group（96.7 ± 17.1,102.5 ± 8.3,106.4 ± 6.5,110.2 ± 9.3,102.4 ± 4.7,102.5 ± 9.8, all P〈 0.05）. The positive stained neurons of total-JNK also distributed in the same brain regions of rats, but no difference was detected between the rats with fluorosis and controls（all P 〉 0.05）. The increased level of phospho-JNK was positively correlated with the fluoride contents in blood of the rats with fluorosis （r = 0.677）. Conclusions The expression of phospho-JNK in brains of rats with fluorosis was significantly increased with a correlation to fluoride content in blood, which might be connected to the mechanism of neural impairment induced by chronic fluorosis. Key words: Fluoride poisoning; Rats; JNK mitogen-activated protien kinases