ABSTRACT
Fluoride could cause developmental neurotoxicity and significantly affect the intelligence quotient (IQ) of children. However, the systematic mechanism of neuronal damage caused by excessive fluoride administration in offspring is largely unknown. Here, we present a comprehensive integrative transcriptome and metabolome analysis to study the mechanism of developmental neurotoxicity caused by chronic fluoride exposure. Comparing the different doses of fluoride treatments in two generations revealed the exclusive signature of metabolism pathways and gene expression profiles. In particular, neuronal development and synaptic ion transport are significantly altered at the gene expression and metabolite accumulation levels for both generations, which could act as messengers and enhancers of fluoride-induced systemic neuronal injury. Choline and arachidonic acid metabolism, which highlighted in the integrative analysis, exhibited different regulatory patterns between the two generations, particularly for synaptic vesicle formation and inflammatory factor transport. It may suggest that choline and arachidonic acid metabolism play important roles in developmental neurotoxic responses for offspring mice. Our study provides comprehensive insights into the metabolomic and transcriptomic regulation of fluoride stress responses in the mechanistic explanation of fluoride-induced developmental neurotoxicity.
Subject(s)
Fluorides , Neurotoxicity Syndromes , Humans , Child , Mice , Animals , Fluorides/toxicity , Transcriptome , Arachidonic Acid , Metabolome , Neurotoxicity Syndromes/genetics , Choline , BrainABSTRACT
Nervonic acid is one of the most promising bioactive fatty acids, which is believed to be beneficial for the recovery of human cognitive disorders. However, the detailed neuroprotective effects and mode of action of nervonic acid have not yet been fully elucidated. In this study, we used an MPTP-stimulated mouse Parkinson's disease (PD) model as a target to investigate the neuroprotective effects by behavioral tests and integrative analysis of trancriptomes and metabolomes of PD mouse brain with nervonic acid injections. The KEGG pathway enrichment analysis of transcriptomes showed that the genes involved in neuroinflammation were significantly increased after MPTP induction and have been greatly inhibited by nervonic acid injection, while nervonic acid also greatly improved nerve growth and synaptic plasticity pathways which were significantly downregulated by MPTP. At the same time, the upregulation of oleic acid and arachidonic acid metabolism pathways and the downregulation of amino acid metabolism pathways in metabolomes were particularly highlighted in the nervonic acid protection groups compared with the PD model. Meanwhile, it was found that arachidonic acid, oleic acid and taurine play an important regulatory role in the neuroprotective mechanism of nervonic acid through fatty acid metabolism by integrative analysis. Therefore, our study laid a solid foundation for further studies on the specific role of nervonic acid in the inhibition of PD at the level of metabolic regulation.
Subject(s)
Neuroprotective Agents , Parkinson Disease , Humans , Animals , Mice , Parkinson Disease/drug therapy , Parkinson Disease/genetics , Transcriptome , Neuroinflammatory Diseases , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Arachidonic Acids , Oleic Acids , Mice, Inbred C57BL , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/adverse effects , Disease Models, AnimalABSTRACT
OBJECTIVE: To investigate the shaping effects of three nickel-titanium rotary instruments on preparing curved canals in posterior teeth. METHODS: 64 curved mesial canals of extracted lower molars, embedded in the Branmante models, were randomly assigned to four groups: (1) Flexofile; (2) LightSpeed; (3) ProFile; (4) Qantec SC. Apical preparation was carried out till size 30. The area of dentine removal, least remaining dentine thickness and transportation of canal center were measured. RESULTS: Flexofile resulted in more dentine removal and canal center transportation than LightSpeed and ProFile (P < 0.05) at the apical and mid-root levels. In the mid-root sections, Flexofile left the thinnest dental wall in the distal aspect; 87% of the canal centers in the Flexofile group were transported in a distal direction as compared with one third in other groups. CONCLUSIONS: LightSpeed and ProFile exhibited better shaping ability than Flexofile in preparing curved canals.
