Effect Of Subchronic Exposure To Arsenic On Thyroid Hormone Receptor Expression In Brain Tissue In Mice

Background: Arsenic(As) is one of the most common heavy metal contaminants found in the environment, particularly in water. Many investigations have demonstrated that arsenic causes neurotoxicity including impairment of learning and deterioration in pattern memory in humans and animals. Our previous study also showed that bothαandβisoforms of Camk4 protein were decreased. It was strongly suggested that impair motor-learning and memory and repress the LTD pathway via downregulating Camk4 expression. However, how As affected the downregulated expression of Ca2+/calmodulin dependent protein kinase IV(Camk4)?Objective: The present study was to elucidate whether low-dose exposure to arsenic would affect thyroid hormone receptor expression in brain tissue in mice, and presume whether the expression of thyroid hormone receptor would affect the downregulated expression of Ca2+/calmodulin dependent protein kinase IV(Camk4). Methods: 50 SPF mice were randomly divided into five groups: the control group,1 ppm As₂O₃,2 ppm As₂O₃,4 ppm As₂O₃,both of 4 ppm As₂O₃ and 150 mg/kg taurine. Then their behaviors of learning and memory were tested by step-down test, passive avoidance test and Morris water maze experiment. The critical gene expression profiles related to thyroid hormone receptor in brain tissue were analyzed by GeneChip and PCR method. We further analyzed the influence of As on brain thyroid hormone receptor expression using Western blot method.Results: Step-down test showed that the mice in the experimental groups made notable errors compared with the control group(P<0.05) and the incubation period (jumping from the platform) significantly reduced (P<0.05). Passive avoidance test showed that compared with the control group, mice in the experimental groups made notable errors(P<0.05) and the incubation period(entering in dark chamber from light chamber) significantly reduced(P<0.05). Morris water maze test indicated that the mice in the groups exposed to As exhibited longer escape latency to find the hidden platform than control group(P<0.05). Our results showed that TRβwas down-regulated in brain tissue of mice exposed to As using Real Time PCR method, confirming the result of GeneChip. We further analyzed the in?uence of As on brain TR expression using Western blot method. The quantity of TRβ1 band in the group exposed to 4 ppm As₂O₃ significantly decreased compared to the control group,1 ppm or 2 ppm group, agreeing well with the gene microarray result. Furthermore, the intervening experiment showed that the coadministered antioxidant taurine scavenging ROS in vivo partly rescued TRβ1 expression.Conclusion: Arsenic exposure can cause learning and memory abilities decline in mice. It is strongly suggested that As accumulated in brain tissue of mice chronically exposed to As and the deposited As impeded the TRβ1 expression. Therefore, the TRβ1 may be target of As-induced neurotoxicity. Furthermore, the intervention of antioxidants taurine prevent TRβ1 from downregulation, indicating that the downregulation of TRβ1 expression by As may be via a oxidation- independent way.