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

Liang, L-X and Liang, J and Li, Q-Q and Zeeshan, M and Zhang, Z and Jin, N and Lin, L-Z and Wu, L-Y and Sun, M-K and Tan, W-H and Zhou, Y and Chu, C and Hu, L-W and Liu, R-Q and Zeng, X-W and Yu, Y and Dong, G-H (2023) Early life exposure to F-53B induces neurobehavioral changes in developing children and disturbs dopamine-dependent synaptic signaling in weaning mice. In: Environment International, 181 .

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Abstract

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. © 2023 The Author(s)

Item Type:	Journal Article
Publication:	Environment International
Publisher:	Elsevier Ltd
Additional Information:	The copyright for this article belongs to authors.
Keywords:	Amines; Mammals; Neurophysiology; Polymerase chain reaction, Card-sorting; Confidence interval; Dopamine; Earliest life; F-53b; Guangzhou; Neurobehavioural; Neurotoxicity; Synaptic plasticity; WISCONSIN, Proteins, brain derived neurotrophic factor; dopamine; dopamine transporter; f 53b; neuromodulin; neurotoxin; unclassified drug; alkanesulfonic acid; dopamine; fluorocarbon, behavioral response; child health; epidemiology; experimental study; neurology; protein; toxicity, Article; behavior change; blood level; breast milk; child; China; controlled study; dopamine metabolism; escape latency; female; hippocampus; human; Morris water maze test; mouse; nerve cell differentiation; nerve cell plasticity; neurotoxicity; nonhuman; perinatal exposure; placental transfer; protein expression; real time polymerase chain reaction; sucking; synaptic transmission; upregulation; weaning; Western blotting; Wisconsin Card Sorting Test; animal; chemistry; metabolism; placenta; pregnancy; water pollutant; zebra fish, China; Guangdong; Guangzhou, Alkanesulfonates; Alkanesulfonic Acids; Animals; Child; Dopamine; Female; Fluorocarbons; Humans; Mice; Placenta; Pregnancy; Water Pollutants, Chemical; Weaning; Zebrafish
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	10 Dec 2024 18:06
Last Modified:	10 Dec 2024 18:06
URI:	http://eprints.iisc.ac.in/id/eprint/85383

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