Fetal exposure to dichloroacetic acid and impaired cognitive function in the adulthood. Issue 10 (25th August 2020)

• Record Type: Journal Article
• Authors: Wang, Yue; Jiang, Wenbo; Dong, Qiuying; Zhao, Yue; Chen, Yingying; Sun, Changhao; Sun, Guoli
• Is Part Of: Brain and behavior. Volume 10:Issue 10(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-08-25
• Subjects: BDNF -- dichloroacetic acid -- hippocampus -- neuroinflammation -- oxidative stress -- synaptic plasticity; Neurology -- Periodicals; Neurosciences -- Periodicals; Psychology -- Periodicals; Psychiatry -- Periodicals; 616.8005
• DOI: 10.1002/brb3.1801
• Languages: English
• ISSNs: 2162-3279

Abstract

Abstract: Introduction: Dichloroacetic acid (DCA), a by‐product of disinfection in drinking water, is a multiple organ carcinogen in humans and animals. Still, little research on its neurotoxicity and its underlying mechanism has not been elucidated. Methods: Sprague Dawley rats were intragastrically treated with DCA at 10, 30, 90 mg/kg body weight from pregnancy till delivery. At eight weeks of age of pups, we assessed cognitive performance using the standard behavioral tests. And the hippocampus structure and ultrastructure were evaluated using light and electron microscope. The oxidative stress indicators and neuroinflammation factors were measured with the corresponding kits. The mRNA and protein of synaptic factors were detected using RT‐PCR and Western blot. Results: The results indicated that maternal weight gain and offspring birthweight were not significantly affected by DCA. However, behavioral tests, including morris water maze and step down, showed varying degrees of changes in DCA‐treated pups. Additionally, we found significant differences in hippocampal neurons by histomorphological observation. Biochemical analysis results indicated superoxide dismutase (SOD) and catalase (CAT) activities, as well as reactive oxygen species (ROS), nitric oxide (NO), and reduced glutathione (GSH) levels, were affected by DCA accompanying with DNA damage. Moreover, the results showed that the neuroinflammation factors (TNF‐α, IL‐6, IL‐1β) in DCA treatment groups increased significantly compared with the control pups. And we also found that DCA treatment caused a differential modulation of proteins (BDNF, cAMP‐response element‐binding protein1 (CREB1), p‐CREB1, postsynaptic density‐95 (PSD‐95), synapsin I, p‐synapsin I), and mRNA (BDNF, PSD‐95). Conclusions: Taken together, these results above showed that oxidative stress, neuroinflammation response, and weakened synaptic plasticity in pups hippocampus induced by fetal exposure to DCA could damage the function of memory and cognition in the adulthood. Abstract : There are still no evidence reporting whether DCA could hamper the memory and cognitive function, and it is still largely unknown whether the roots of impaired cognitive function extend back to exposure to DCA during early life.Therefore, we proposed hypothesis that fetal exposure to DCA may cause oxidative stress, inflammatory response, and damaged neurotrophic factors, which could interrelate to affect synaptic plasticity and cognition function in the adulthood.