Maternal transfer of F-53B inhibited neurobehavior in zebrafish offspring larvae and potential mechanisms: Dopaminergic dysfunction, eye development defects and disrupted calcium homeostasis.

Maternal exposure to environment toxicants is an important risk factor for neurobehavioral health in their offspring. In our study, we investigated the impact of maternal exposure to chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs, commercial name: F-53B) on behavioral changes and the potential mechanism in the offspring larvae of zebrafish. Adult zebrafish exposed to Cl-PFESAs (0, 0.2, 2, 20 and 200 µg/L) for 21 days were subsequently mated their embryos were cultured for 5 days. Higher concentrations of Cl-PFESAs in zebrafish embryos were observed, along with, reduced swimming speed and distance travelled in the offspring larvae. Molecular docking analysis revealed that Cl-PFESAs can form hydrogen bonds with brain-derived neurotropic factor (BDNF), protein kinase C, alpha, (PKCα), Ca2+-ATPase and Na, K - ATPase. Molecular and biochemical studies evidenced Cl-PFESAs induce dopaminergic dysfunction, eye developmental defects and disrupted Ca2+ homeostasis. Together, our results showed that maternal exposure to Cl-PFESAs lead to behavioral alteration in offspring mediated by disruption in Ca2+ homeostasis, dopaminergic dysfunction and eye developmental defects.

Early life exposure to F-53B induces neurobehavioral changes in developing children and disturbs dopamine-dependent synaptic signaling in weaning mice.

BACKGROUND: Previous studies have shown that F-53B exposure may be neurotoxic to animals, but there is a lack of epidemiological evidence, and its mechanism needs further investigation. METHODS: Serum F-53B concentrations and Wisconsin Card Sorting Test (WCST) were evaluated in 314 growing children from Guangzhou, China, and the association between them were analyzed. To study the developmental neurotoxicity of F-53B, experiments on sucking mice exposed via placental transfer and breast milk was performed. Maternal mice were orally exposed to 4, 40, and 400 µg/L of F-53B from postnatal day 0 (GD0) to postnatal day 21 (PND 21). Several genes and proteins related to neurodevelopment, dopamine anabolism, and synaptic plasticity were examined by qPCR and western blot, respectively, while dopamine contents were detected by ELISA kit in weaning mice. RESULTS: The result showed that F-53B was positively associated with poor WCST performance. For example, with an interquartile range increase in F-53B, the change with 95 % confidence interval (CI) of correct response (CR), and non-perseverative errors (NPE) was -2.47 (95 % CI: -3.89, -1.05, P = 0.001), 2.78 (95 % CI: 0.79, 4.76, P = 0.007), respectively. Compared with the control group, the highest exposure group of weaning mice had a longer escape latency (35.24 s vs. 51.18 s, P = 0.034) and a lesser distance movement (34.81 % vs. 21.02 %, P < 0.001) in the target quadrant, as observed from morris water maze (MWM) test. The protein expression of brain-derived neurotrophic factor (BDNF) and growth associated protein-43 (GAP-43) levels were decreased, as compared to control (0.367-fold, P < 0.001; 0.366-fold, P < 0.001; respectively). We also observed the upregulation of dopamine transporter (DAT) (2.940-fold, P < 0.001) consistent with the trend of dopamine content (1.313-fold, P < 0.001) in the hippocampus. CONCLUSION: Early life exposure to F-53B is associated with adverse neurobehavioral changes in developing children and weaning mice which may be modulated by dopamine-dependent synaptic plasticity.

[Changes of regional environment quality pattern in China since 1986-2008].

For further study of regional differences and the pattern of changes in environmental quality in China since 1986-2008, we perform the principal component analysis, standard deviation, Mann-Kendall and cluster analysis on 18 environmental quality indexes in 28 provinces of China in this paper. Those indexes refer to pollutant emission, pollutants treatment capacities and pollutant emission of per unit land area, etc. The paper indicates that regional environmental quality in China has been increased slightly during this period. It can be divided into four stages: 1986-2000, 2000-2001, 2001-2005 and 2005-2008. The overall patterns of regional environmental quality is the West is higher than the East in general, while the environmental quality of the eastern part have been changed somewhat. For more details, the regional environmental quality in China in 1986 is composed of two parts, the eastern part and the western part, while in 2000 and 2001 the eastern part, the middle part and the western part appears as the overall pattern. For the year of 2005, the regional environmental quality in the western is higher than that of the eastern; meanwhile, the eastern can be divided into the northern part, the middle part and the southern part, and the environmental quality in northern part is better than that of the southern part, southern part is better than that of the middle part. This pattern hardly changed in 2008, except that the area with poor environment quality region had expanded. Pollutant emission of per unit land area played as a main factor; yet both the pollutant emission and the reuse of pollutants impacted the pattern specifically. In addition, the national macro policies, the regional policies, the regional economic and the industrial structure can be primary reason for the change of regional environmental quality pattern in China as well.