硒代蛋氨酸通过PINK1/Parkin介导的线粒体自噬缓解氟诱导的抑郁样行为OA北大核心CSTPCD

This experiment aims to investigate the role of PINK1/Parkin-mediated mitochondrial autophagy in the alleviation of fluoride-induced depressive-like behavior by selenomethionine(Se-Met).Forty BALB/c mice were selected and randomly divided into five groups:the blank control group(Group C),the fluorine group(NaF 150 mg·L-1,Group F),the fluorine+low selenium group(NaF 150 mg·L-1+1.5 mg·L-1,Group F+LSe),the fluorine+medium selenium group(NaF 150 mg·L-1+3.0 mg·L-1,Group F+MSe),the fluorine+high selenium group(NaF 150 mg·L-1+6.0 mg·L-1,Group F+HSe).After 90 d of sodium fluoride exposure,the behavioral performance of mice was assessed by means of an elevated O-maze and hanging tail experiments;HE staining was used to evaluate the damage of the mouse cortex;biochemical kits were used to measure the content of oxidative stress-related indices;and real-time fluorescence quantitative PCR was utilized to determine the expression levels of mitochondrial autophagy-related genes.Animal behavioral results showed:the results indicated that mice in group F had a significantly longer"resting"time in the tail suspension test compared to group C(P＜0.05)and a tendency to take more time to enter the closed arm of the elevated O-maze(P＜0.05).After Se-Met supplementation,the"resting"time of mice was reduced significantly(P＜0.05),and the F+LSe and F+MSe mice took significantly less time to enter the closed arm(P＜0.05),compared to the F group.The results of the histopathological sections showed:the mice in group F had disorganized cortical cells,reduced cell volume,and fewer vertebral cells.Following Se-Met enhancement,the F+LSe group showed distinct nuclei and more uniform cytoplasm,and the improvement was notably more pronounced.The results of oxidative stress related indicators showed:group F had a significantly higher level of reactive oxygen species(ROS)(P＜0.05),and a significantly reduced content of glutathione peroxidase(GSH-PX)(P＜0.05),when compared to group C.Groups F+LSe,F+HSe,and F+MSe showed significantly lower levels of ROS(P＜0.05).Compared to group F,the ROS content was considerably lower(P＜0.05),in groups F+LSe,F+HSe,and F+MSe,with the content decreasing in the order of F+LSe＜F+HSe＜F+MSe;the GSH-PX content,on the other hand,was significantly higher(P＜0.05),in groups F+LSe and F+HSe,compared to group F.Results of mRNA expression levels of autophagy-related genes were shown:group F showed significantly higher mRNA expression levels of autophagy-related genes Parkin,PINK1,LC3,OPTN,NBR1,Drp1,and Fis1(P＜0.05),compared to group C,and significantly lower mRNA expression levels of OPA1,Mfn1,and Mfn2(P＜0.05).Compared to group F,the mRNA expression levels of Parkin,PINK1,P62,NBR1,OPTN,and Fis1 were significantly lower in the F+LSe and F+HSe groups(P＜0.05),LC3,Parkin,P 62 and Drp1 were significantly decreased in the F+LSe and F+MSe groups(P＜0.05),OPA1 was significantly increased(P＜0.05),and the F+LSe group showed a significant increase in the mRNA expression level of Mfn2(P＜0.05).In summary,1.5 mg·L-1 of Se-Met can alleviate cortical oxidative stress by affecting the expression of mitochondrial autophagy-related genes,restoring the dynamic equilibrium state of mitochondrial fusion and fission,and thus ameliorating cerebral cortex damage and the emergence of depressive-like behaviors.