Chronic Exposure To Low Levels Of Copper Accelerated Anxiety And Depression-like Behaviors And Altered Amygdala Proteins Expression In Transgenic Mice Of Alzheimer’s Disease

Objective:With the development of the society and the progress of medical conditions, neuropsychiatric disorders including Schizophrenia, Parkinson’s disease, Alzheimer’s disease and other diseases of the nervous system have become the main diseases impairing human health in 21st century. Exposure to low levels of copper would accelerate the development of anxiety and depression; however, the potential mechanisms remain unclear. The purpose of this study is to explore the effects of chronic exposure to low levels of copper on anxiety and depression. The accomplishment of this study would be expected to provide scientific evidence for the health risk assessment on copper exposure.Methods:In this study, we treated WT mice and Tg mice (3 month-old of age) with 0.13 ppm copper chloride in drinking water for 8 months. The open field test, elevated plus-maze test and the light/dark box test were employed to meaure the effects of chronic low level copper exposure on anxiety disorder; the forced swimming test and tail suspension test were employed to measure the effects of copper exposure on depression behavior. Then, we used iTRAQ and 2D-DIGE coupled with mass spectrometry to reveal the potential proteins molecules involved in the effects of chronic low-level copper exposure on anxienty and depression behaviors. Western-blot analysis was used to further verify the expression of the proteins.Results:The behavior tests showed that chronic exposure to low levels of copper caused anxiety and depression-like behaviors in WT mice, and worsened depression-like behavior in Tg mice. iTRAQ coupled with mass spectrometry revealed a total of 246 differentially expressed proteins in amygdala between the WT mice and Tg mice; a total of 152 differentially expressed proteins in amygdala between Cu-treated WT mice and WT mice; a total of 210 differentially expressed proteins in amygdala between Cu-treated Tg mice and Tg mice. Protein functional enrichment analysis showed that these differentially expressed proteins were related to metabolic processes, apoptosis, biological regulations, etc.9 hippocampal proteins were found abnormally expressed between the Tg mice and WT mice. Among these differentially expressed proteins SRR and GFAP were verified by Western-blot analysis.Conclusion:Taken together, our data suggested that chronic exposure to low-levels of copper caused anxiety and depression-like behaviors in WT mice, and aggravated depression-like behavior in Tg mice. Chronic exposure to low-level copper altered the expression of proteins in amygdala and hippocampus of both WT mice and Tg mice. Some differentially expressed proteins were closely related to neuropsychiatric disorders.