[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 mitochondrial fission 1 (Fis1) 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 COXIV and tubulin-α were captured with fluorescence microscope. Fis1 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 COXIV(34.8 ± 4.7 and 39.3 ± 3.0, respectively), and the expression of Fis1 protein (immunohistochemistry: 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 compared with controls (4.4 ± 2.3, 25.2 ± 2.5, 1.8 ± 0.2 and 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 Fis1 gene and enhanced mitochondrial fission. The altered mitochondrial distribution may be related to the high expression level of Fis1 and a functional disorder of mitochondria.
Department of Pathology and Key Lab of Molecular Biology, Guiyang Medical College, Guiyang 550004, China.
Di-dong
DD
Lou
Kai-lin
KL
Zhang
Shuang-li
SL
Qin
Yan-fei
YF
Liu
Yan-ni
YN
Yu
Zhi-zhong
ZZ
Guan
D000818:Animals; D001369:Axons / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism; D060766:Drinking Water / Q000009:adverse effects / Q000737:chemistry; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D005459:Fluorides / Q000009:adverse effects / Q000652:urine; D009050:Fluorosis, Dental / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008928:Mitochondria / Q000473:pathology*; D063154:Mitochondrial Dynamics / Q000187:drug effects*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014404:Tubulin / Q000378:metabolism
D060766:Drinking Water; C503403:Fis1 protein, rat; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D014404:Tubulin; D003576:Electron Transport Complex IV; D005459:Fluorides