Elevated Level of PINK1/Parkin-Mediated Mitophagy Pathway Involved to the Inhibited Activity of Mitochondrial Superoxide Dismutase in Rat Brains and Primary Hippocampal Neurons Exposed to High Level of Fluoride.

To reveal the molecular mechanism of brain damage induced by chronic fluorosis, expression of PTEN-induced kinase 1 (PINK1)/parkin RBR E3 ubiquitin-protein ligase (Parkin)-mediated mitophagy pathway and activity of mitochondrial superoxide dismutase (SOD) were investigated in rat brains and primary cultured neurons exposed to high level of fluoride. Sprague-Dawley (SD) rats were treated with fluoride (0, 5, 50, and 100 ppm) for 3 and 6 months. The primary neurons were exposed to 0.4 mM (7.6 ppm) fluoride and thereafter treated with 100 nM rapamycin (a stimulator of mitophagy) or 50 µM 3-methyladenine (3-MA, an inhibitor of mitophagy) for 24 h. The expressions of PINK1/Parkin at the protein level and the activity of SOD in mitochondria of rat brains and cultured neurons were determined by Western blotting and biochemical method, respectively. The results showed that the rats exposed to fluoride exhibited different degrees of dental fluorosis. In comparison to controls, the expressions of PINK1 and Parkin were significantly higher in the rat brains and primary neurons exposed to high fluoride. In addition, a declined activity of mitochondrial SOD was determined. Interestingly, rapamycin treatment enhanced but 3-MA inhibited the changes of PINK1/Parkin pathway and SOD activity, and the correlations between the inhibited SOD activity and the elevated PINK1/Parkin proteins were observed. The results suggest that the inhibition of mitochondrial SOD activity induced by fluorosis may stimulate the expressions of mitophagy (PINK1/ Parkin) pathway to maintain the mitochondrial homeostasis.

Association Between Different Indicators of Obesity and Depression in Adults in Qingdao, China: A Cross-Sectional Study.

Background: This study was designed to investigate the perceived relationship between body weight and depression risk in a Chinese population in Qingdao, China. Methods: A population-based cross-sectional survey was performed with 4,573 participants (between 35 and 74 years) from the year 2009 to 2012 in Qingdao, China. We applied the Zung self-rating depression scale to ascertain the level of depression in participants. The associations between different indicators of obesity [body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR)] and depression were assessed by logistic regression based on the Chinese criteria of obesity. Sensitivity analysis was done based on the Asian and WHO criteria of obesity. Results: The Zung scores for the 243 participants (5.2%) were over 45 and they were entitled as depression. Furthermore, multivariable logistic analyses revealed that being overweight [odds ratios (OR): 1.48, 95% confidence intervals [95% CI]: 1.08-2.03] and having abdominal obesity (WC category in Chinese criteria) (OR: 1.47, 95% CI: 1.08-2.00) were often associated with a higher risk for depression compared to normal weight subjects. Sensitivity analysis revealed that abdominal obesity (Asian criterion) (OR: 1.41, 95% CI: 1.03-1.91) was a significant risk factor for depression. Similarly, being overweight (WHO criterion) (OR: 1.39, 95% CI: 1.03-1.87) was an obvious risk factor for depression. Conclusion: Being overweight and having abdominal obesity (WC category) were found to be linked with a higher risk of depression. However, abdominal obesity (WHR category) was not associated with depression.