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Adenosine A1-Receptors Modulate mTOR Signaling to Regulate White Matter Inflammatory Lesions Induced by Chronic Cerebral Hypoperfusion

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Abstract

We sought to investigate the role of the adenosine A1 receptors (A1ARs) in white matter lesions under chronic cerebral hypoperfusion (CCH) and explore the potential repair mechanisms by activation of the receptors. A right unilateral common carotid artery occlusion (rUCCAO) method was used to construct a CCH model. 2-chloro-N6-cyclopentyladenosine (CCPA), a specific agonist of A1ARs, was used to explore the biological mechanisms of repair in white matter lesions under CCH. The expression of mammalian target of rapamycin (mTOR), phosphorylation of mTOR (P-mTOR), myelin basic protein (MBP, a marker of white matter myelination) were detected by Western-blot. Pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and anti-inflammatory cytokine interleukin-10 (IL-10) levels were determined by ELISA. Compared with the control groups on week 2, 4 and 6, in CCPA-treated groups, the ratio of P-mTOR/mTOR, expression of MBP and IL-10 increased markedly, while the expression of TNF-α reduced at week 6. In conclusion, A1ARs appears to reduce inflammation in white matter via the mTOR signaling pathway in the rUCCAO mice. Therefore, A1ARs may serve as a therapeutic target during the repair of white matter lesions under CCH.

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Acknowledgments

This work was supported by research Grants from the National Natural Science Foundation of China (Grant # 81171113, Grant # 81571129). We thank the laboratory support staff for their help in this study.

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    Authors and Affiliations

    1. Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

      Pengfei Cheng, Yifei Ren, Shunjie Bai & Peng Xie

    2. Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China

      Xuzheng Zuo, Weiju Tang, Xiuying Chen, Gong Wang, Haoxiang Wang & Wen Huang

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    1. Pengfei Cheng
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    2. Xuzheng Zuo
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    Correspondence to Wen Huang or Peng Xie.

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    Pengfei Cheng and Xuzheng Zuo have contributed equally to the work.

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    Cheng, P., Zuo, X., Ren, Y. et al. Adenosine A1-Receptors Modulate mTOR Signaling to Regulate White Matter Inflammatory Lesions Induced by Chronic Cerebral Hypoperfusion. Neurochem Res 41, 3272–3277 (2016). https://doi.org/10.1007/s11064-016-2056-0

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    • DOI: https://doi.org/10.1007/s11064-016-2056-0

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