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Anti-inflammatory Effect of Astaxanthin on the Sickness Behavior Induced by Diabetes Mellitus

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Abstract

Chronic inflammation appears to play a critical role in sickness behavior caused by diabetes mellitus. Astaxanthin has been used in treating diabetes mellitus and diabetic complications because of its neuroprotective and anti-inflammatory actions. However, whether astaxanthin can improve sickness behavior induced by diabetes and its potential mechanisms are still unknown. The aim of this study was to investigate the effects of astaxanthin on diabetes-elicited abnormal behavior in mice and its corresponding mechanisms. An experimental diabetic model was induced by streptozotocin (150 mg/kg) and astaxanthin (25 mg/kg/day) was provided orally for 10 weeks. Body weight and water consumption were measured, and the sickness behavior was evaluated by the open field test (OFT) and closed field test (CFT). The expression of glial fibrillary acidic protein (GFAP) was measured, and the frontal cortical cleaved caspase-3 positive cells, interleukin-6 (IL-6), and interleukin-1β (IL-1β) expression levels were also investigated. Furthermore, cystathionine β-synthase (CBS) in the frontal cortex was detected to determine whether the protective effect of astaxanthin on sickness behavior in diabetic mice is closely related to CBS. As expected, we observed that astaxanthin improved general symptoms and significantly increase horizontal distance and the number of crossings in the OFT and CFT. Furthermore, data showed that astaxanthin could decrease GFAP-positive cells in the brain and down-regulate the cleaved caspase-3, IL-6, and IL-1β, and up-regulate CBS in the frontal cortex. These results suggest that astaxanthin provides neuroprotection against diabetes-induced sickness behavior through inhibiting inflammation, and the protective effects may involve CBS expression in the brain.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (81371300), the Education Departmental Natural Science Research Funds of Jiangsu Provincial Higher School of China (13KJB310021, 13KJD310003), the Project of Xuzhou science and technology plan (KC14SH076), the Foundation of President of Xuzhou Medical College (2012KJZ06), a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and the Qing Lan Project of Jiangsu Province. Thanks to Hongyan Dong, Hongli Yu, Meng Wang, Baole Zhang and Xuebin Qu for their support and help during the experiments.

Conflict of interest

All authors state that they have no conflict of interest in the present study.

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    Authors and Affiliations

    1. Department of Endocrinology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, Jiangsu, People’s Republic of China

      Chang-jiang Ying

    2. Laboratory of Morphology, Xuzhou Medical College, Xuzhou, 221004, Jiangsu, People’s Republic of China

      Fang Zhang, Xiao-yan Zhou, Xiao-tong Hu, Jing Chen & Ren-xian Tang

    3. Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou, 221004, Jiangsu, People’s Republic of China

      Xiang-ru Wen & Yuan-jian Song

    4. Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, Jiangsu, People’s Republic of China

      Ying Sun

    5. Department of Genetics, Research Center for Neurobiology, Xuzhou Medical College, Xuzhou, 221004, Jiangsu, People’s Republic of China

      Yuan-jian Song

    6. Department of Pathogen Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical College, Xuzhou, 221004, Jiangsu, People’s Republic of China

      Kui-yang Zheng & Ren-xian Tang

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    Chang-jiang Ying, Fang Zhang, Xiao-yan Zhou have contributed equally to this work.

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    Ying, Cj., Zhang, F., Zhou, Xy. et al. Anti-inflammatory Effect of Astaxanthin on the Sickness Behavior Induced by Diabetes Mellitus. Cell Mol Neurobiol 35, 1027–1037 (2015). https://doi.org/10.1007/s10571-015-0197-3

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