Gene-Expression Changes in Cerium Chloride-Induced Injury of Mouse Hippocampus

Abstract

Cerium is widely used in many aspects of modern society, including agriculture, industry and medicine. It has been demonstrated to enter the ecological environment, is then transferred to humans through food chains, and causes toxic actions in several organs including the brain of animals. However, the neurotoxic molecular mechanisms are not clearly understood. In this study, mice were exposed to 0.5, 1, and 2 mg/kg BW cerium chloride (CeCl3) for 90 consecutive days, and their learning and memory ability as well as hippocampal gene expression profile were investigated. Our findings suggested that exposure to CeCl3 led to hippocampal lesions, apoptosis, oxidative stress and impairment of spatial recognition memory. Furthermore, microarray data showed marked alterations in the expression of 154 genes involved in learning and memory, immunity and inflammation, signal transduction, apoptosis and response to stress in the 2 mg/kg CeCl3 exposed hippocampi. Specifically, the significant up-regulation of Axud1, Cdc37, and Ube2v1 caused severe apoptosis, and great suppression of Adcy8, Fos, and Slc5a7 expression led to impairment of mouse cognitive ability. Therefore, Axud1, Cdc37, Ube2v1, Adcy8, Fos, and Slc5a7 may be potential biomarkers of hippocampal toxicity caused by CeCl3 exposure.

Kidney injury and alterations of inflammatory cytokine expressions in mice following long-term exposure to cerium chloride

“…The studies on the toxicology of Ln showed that Ln 3+ had adverse effects on various organs as well as the nervous system of animals, e.g., the lesion caused by Ln showed oxidative stress, and histopathological changes (Li et al, ; Liu et al, ; Cheng et al, ; Fei et al, ; Zhao et al, , ; Cheng et al, , ; Wang et al, ). In this study, our data suggested that CeCl 3 exposure led to severe oxidative stress, including over production of O 2 − and H 2 O 2 , and peroxidation of lipid, protein, and DNA in the kidney (Table ), which were related to inflammatory response and necrosis of kidneys (Fig.…”

“…Numerous studies have shown that Ln exposure is able to cause injuries in various animal organ types, including liver (Lu and Ni, ; Wu et al, ; Kawagoe et al, ; Ze et al, ; Fei et al, , ; Cheng et al, , , ; Zhao et al, ; Li et al, ), lung (Kawagoe et al, ; Li et al, ), spleen (Liu et al ; Cheng et al ), and brain (Zhu et al, ; Feng et al, ; Zhao et al, , ; Cheng et al, , ; Wang et al, ). Specifically, the toxicity of Ln to kidney has been also reported.…”

Investigation of rare earth elements in urine and drinking water of children in mining area

“…Moreover, in vitro tests showed that lanthanum nitrate could cut off the DNA strand and cause genetic damage. Cheng et al [ 12 ] demonstrated that mice continuously exposed to Ce chloride for 90 days showed cell apoptosis, oxidative stress, and space memory impairment in the hippocampus, and altered expression profiles of immune- and inflammatory response–related genes. Kumari et al [ 13 ] found that high-dose Ce oxide nanoparticles could induce DNA damage in peripheral blood leukocytes and micronuclei changes in hepatocytes, blood cells, and bone marrow cells.…”

Molecular neurochemistry of the lanthanides

“…Another study by Zheng et al () reports that the exposure of CeCl 3 in mice increases oxidative stress in the hippocampus, besides altering 154 genes involved in multiple processes such as learning and memory, programmed neuron death, response to stress, immunity, and inflammation. A study by Cheng et al () reports that long‐term exposure to CeCl 3 supports ROS production and triggers apoptosis in the mouse hippocampus. Ce 3+ significantly increased the expression of apoptosis‐related genes, e.g., antagonizing transcription factor (TRB), ubiquitin‐conjugating enzyme e2 (UBE2V1), cysteine‐serine‐rich nuclear protein1 (AXUD1), and cell division 37 homolog (CDC37).…”

“…Another study by Zheng et al (2013) reports that the exposure of CeCl 3 in mice increases oxidative stress in the hippocampus, besides altering 154 genes involved in multiple processes such as learning and memory, programmed neuron death, response to stress, immunity, and inflammation. A study by Cheng et al (2013) reports that long-term exposure to CeCl 3 supports ROS production and triggers apoptosis in the mouse hippocampus.…”