Dataset Information

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 (CeCl(3)) 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 CeCl(3) 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 CeCl(3) 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.

SUBMITTER: Cheng Z

PROVIDER: S-EPMC3616000 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Gene-expression changes in cerium chloride-induced injury of mouse hippocampus.

Cheng Zhe Z Zhao Haiquan H Ze Yuguan Y Su Junju J Li Bing B Sheng Lei L Zhu Liyuan L Guan Ning N Gui Suxin S Sang Xuezi X Zhao Xiaoyang X Sun Qingqing Q Wang Ling L Cheng Jie J Hu Renping R Hong Fashui F

PloS one 20130403 4

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 (CeCl(3)) for 90 consecutive days, and their learning and mem ...[more]

PMID: 23573234

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Project description:BackgroundDifferential processing of the amyloid precursor protein liberates either amyloid-ß, a causative agent of Alzheimer's disease, or secreted amyloid precursor protein-alpha (sAPP?), which promotes neuroprotection, neurotrophism, neurogenesis and synaptic plasticity. The underlying molecular mechanisms recruited by sAPP? that underpin these considerable cellular effects are not well elucidated. As these effects are enduring, we hypothesised that regulation of gene expression may be of importance and examined temporally specific gene networks and pathways induced by sAPP? in rat hippocampal organotypic slice cultures. Slices were exposed to 1 nM sAPP? or phosphate buffered saline for 15 min, 2 h or 24 h and sAPP?-associated gene expression profiles were produced for each time-point using Affymetrix Rat Gene 1.0 ST arrays (moderated t-test using Limma: p?<?0.05, and fold change?±?1.15).ResultsTreatment of organotypic hippocampal slice cultures with 1 nM sAPP? induced temporally distinct gene expression profiles, including mRNA and microRNA associated with Alzheimer's disease. Having demonstrated that treatment with human recombinant sAPP? was protective against N-methyl d-aspartate-induced toxicity, we next explored the sAPP?-induced gene expression profiles. Ingenuity Pathway Analysis predicted that short-term exposure to sAPP? elicited a multi-level transcriptional response, including upregulation of immediate early gene transcription factors (AP-1, Egr1), modulation of the chromatin environment, and apparent activation of the constitutive transcription factors CREB and NF-?B. Importantly, dynamic regulation of NF-?B appears to be integral to the transcriptional response across all time-points. In contrast, medium and long exposure to sAPP? resulted in an overall downregulation of gene expression. While these results suggest commonality between sAPP? and our previously reported analysis of plasticity-related gene expression, we found little crossover between these datasets. The gene networks formed following medium and long exposure to sAPP? were associated with inflammatory response, apoptosis, neurogenesis and cell survival; functions likely to be the basis of the neuroprotective effects of sAPP?.ConclusionsOur results demonstrate that sAPP? rapidly and persistently regulates gene expression in rat hippocampus. This regulation is multi-level, temporally specific and is likely to underpin the neuroprotective effects of sAPP?.

Dataset Information

Gene-expression changes in cerium chloride-induced injury of mouse hippocampus.

Publications

Gene-expression changes in cerium chloride-induced injury of mouse hippocampus.

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