title: The influence of chronic fluorosis on mitochondrial dynamics morphology and distribution in cortical neurons of the rat brain.
abstract: The present study was designed to evaluate the effects of chronic fluorosis on the dynamics (including fusion and fission proteins), fragmentation, and distribution of mitochondria in the cortical neurons of the rat brain in an attempt to elucidate molecular mechanisms underlying the brain damage associated with excess accumulation of fluoride. Sixty Sprague-Dawley rats were divided randomly into three groups of 20 each, that is, the untreated control group (drinking water naturally containing <0.5 mg fluoride/l, NaF), the low-fluoride group (whose drinking water was supplemented with 10 mg fluoride/l) and the high-fluoride group (50 mg fluoride/l). After 6 months of exposure, the expression of mitofusin-1 (Mfn1), fission-1 (Fis1), and dynamin-related protein-1 (Drp1) at both the protein and mRNA levels were detected by Western blotting, immunohistochemistry, and real-time PCR, respectively. Moreover, mitochondrial morphology and distribution in neurons were observed by transmission electron or fluorescence microscopy. In the cortices of the brains of rats with chronic fluorosis, the level of Mfn1 protein was clearly reduced, whereas the levels of Fis1 and Drp1 were elevated. The alternations of expression of the mRNAs encoding all three of these proteins were almost the same as the corresponding changes at the protein levels. The mitochondria were fragmented and the redistributed away from the axons of the cortical neurons. These findings indicate that chronic fluorosis induces abnormal mitochondrial dynamics, which might in turn result in a high level of oxidative stress.
authors.affiliation: Department of Pathology, Guiyang Medical University, Guiyang, 550004, People's Republic of China.
authors.forename: Di-Dong
authors.initials: DD
authors.lastname: Lou
authors.forename: Zhi-Zhong
authors.initials: ZZ
authors.lastname: Guan
authors.forename: Yan-Jie
authors.initials: YJ
authors.lastname: Liu
authors.forename: Yan-Fei
authors.initials: YF
authors.lastname: Liu
authors.forename: Kai-Lin
authors.initials: KL
authors.lastname: Zhang
authors.forename: Ji-Gang
authors.initials: JG
authors.lastname: Pan
authors.forename: Jin-Jing
authors.initials: JJ
authors.lastname: Pei
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D005260:Female; D009050:Fluorosis, Dental / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D063154:Mitochondrial Dynamics / Q000187:drug effects*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012969:Sodium Fluoride / Q000633:toxicity*; D013997:Time Factors
chemical_list: C503403:Fis1 protein, rat; D008565:Membrane Proteins; C489709:Mfn1 protein, rat; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D012969:Sodium Fluoride; C519851:Dnm1l protein, rat; D034281:Dynamins