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Role of PTEN-Akt-CREB Signaling Pathway in Nervous System impairment of Rats with Chronic Arsenite Exposure

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Abstract

The nervous system is a target of arsenic toxicity. Phosphatase and tensin homologue deleted on chromosome 10/protein kinase B/cAMP-response element binding protein (PTEN/Akt/CREB) signaling pathway has been reported to be involved in maintaining normal function of the nervous system, modulating growth and proliferation of neurocyte, regulating neuron synaptic plasticity, and long-term memory. And many studies have demonstrated that expressions of PTEN, Akt, and CREB protein were influenced by arsenic, but it is not clear whether this signaling pathway is involved in the nervous system impairment of rats induced by chronic arsenite exposure, and we have addressed this in this study. Eighty male Sprague-Dawley (SD) rats were randomly divided into eight groups (n = 10 each), four groups exposed to NaAsO2 (0, 5, 10, and 50 mg/L NaAsO2 in drinking water) for 3 months, the other four groups exposed to NaAsO2 (0, 5, 10, 50 mg/L NaAsO2 in drinking water) for 6 months. Hematoxylin and eosin (HE) staining showed that chronic arsenite exposure induced varying degrees of damage in cerebral neurons. And arsenite exposure increased arsenic amount in serum and brain samples in a dose- and time-dependent manner. Moreover, the protein levels of PTEN and Akt in brain tissue were not significantly changed compared with the control group, but p-Akt, CREB, and p-CREB were all significantly downregulated in arsenite-exposed groups with a dose-dependent pattern. These results suggested that chronic arsenite exposure negatively regulated the PTEN-Akt-CREB signaling pathway, and dysfunction of the signaling pathway might be one of the mechanisms of nervous system impairment induced by chronic arsenite exposure.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant no. 81273013).

Conflict of Interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Key Lab of Etiologic Epidemiology of Ministry of Health and Education Bureau of Heilongjiang Province(23618504), Harbin Medical University, 157 Baojian Road, Harbin, 150081, China

    Lisha Qu, Yanhui Gao, Hongna Sun, Hui Wang, Xiaona Liu & Dianjun Sun

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  1. Lisha Qu
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  2. Yanhui Gao
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  3. Hongna Sun
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  4. Hui Wang
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Correspondence to Dianjun Sun.

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Qu, L., Gao, Y., Sun, H. et al. Role of PTEN-Akt-CREB Signaling Pathway in Nervous System impairment of Rats with Chronic Arsenite Exposure. Biol Trace Elem Res 170, 366–372 (2016). https://doi.org/10.1007/s12011-015-0478-1

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  • DOI: https://doi.org/10.1007/s12011-015-0478-1

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