Alteration of mitochondrial distribution and gene expression of fission 1 protein in cortical neurons of rats with chronic fluorosis

Objective To investigate the changes of mitochondrial distribution in axon/soma and the expression of mitoehondrial fission 1 ( Fisl ) protein in the cortical neurons of rats with chronic fluorosis.Methods Sixty SD rats were divided into 3 groups (20 each) according to weight hierarchy and fed with different concentrations of fluoride in drinking water (0,10 and 50 mg/L,respectively) for 6 months.Images of mitochondria and tubulin labeled by immunofluorescence COX Ⅳ and tubulin-α were captured with fluorescence microseope. Fisl protein expression in cortical neurons was analyzed with immunohistochemistry and Western blot.The expression of Fis1 mRNA was detected with real-time PCR.Results Varying degrees of dental fluorosis and increased fluoride contents in urine were observed in the rats receiving additional fluoride in drinking water.In the cortical neurons of rats fed with 10 mg/L and 50 mg/L fluoride,the numbers of neuronal soma stained with COX Ⅳ (34.8 ± 4.7 and 39.3 ± 3.0,respectively),and the expression of Fis1 protein ( immunohislochemistry:54.0 ± 3.6 and 51.3 ± 4.1,respectively; Western blot:2.9 ±0.4 and 2.6 ±0.6,respectively) and mRNA (3773 ± 1292 and 1274 ±162,respectively) was markedly increased as eompared with controls (4.4 ± 2.3,25.2 ± 2.5,1.8 ± 0.2and 277± 73 ) over the experimental period of 6 months.Conclusions Excessive intake of fluoride results in an altered mitochondrial distribution in axon and soma in cortical neurons ( i.e.,the increase in soma and the decrease in axon),increased expression of Fisl gene and enhanced mitochondrial fission.The altered mitochondrial distribution may be related to the high expression level of Fisl and a functional disorder of mitochondria. Key words: Cerebral cortex; Genes, mitoehondrial; Animal experimentation; Fluorosis