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Chronic Cerebral Ischemia Induces Downregulation of A1 Adenosine Receptors During White Matter Damage in Adult Mice

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Abstract

The role of A1 adenosine receptors (A1ARs) in the white matter under chronic cerebral ischemic conditions remains unclear. Here, we used right unilateral common carotid artery occlusion (rUCCAO) to construct a chronic cerebral ischemic mouse model. A1AR expression and proteolipid protein (PLP, a marker of white matter myelination) in the corpus callosum were observed by immunoreaction and immunohistochemistry, respectively. Pro-inflammatory interleukin-1β (IL-1β) and anti-inflammatory interleukin-10 (IL-10) levels were determined by ELISA. The Morris water maze test was employed to detect cognitive impairment. A1AR expression significantly decreased in the rUCCAO group as compared with the sham control group on weeks 2, 4, and 6, respectively. IL-10 levels in the rUCCAO group significantly declined on week 6, while there was no significant change in IL-1β expression. PLP expression significantly decreased in the rUCCAO group on weeks 2, 4, and 6. Moreover, latency time for the Morris water maze test significantly increased in the rUCCAO group on weeks 4 and 6, while the number of platform location crossing significantly decreased in the rUCCAO group on weeks 2, 4, and 6. In conclusion, this study provides the first evidence that chronic cerebral ischemia appears to induce A1AR downregulation and inhibition of IL-10 production, which may play key roles in the neuropathological mechanisms of ischemic white matter lesions. These data will facilitate future studies in formulating effective therapeutic strategies for ischemic white matter lesions.

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Acknowledgments

We thank the scientific editors at Impactys (www.impactys.com) for editing and proofreading this manuscript. This work was supported by research grants from the National Natural Science Foundation of China (Grant No. 81171113), the Postdoctoral Fund (Grant No. XM201101003), the National Natural Science Foundation of China (Grant No. 31300881), and the National Basic Research Program of China (973 Program, Grant No. 2009CB918300.).

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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, Yi Xu, Jin Chen, Meiling Liu & Peng Xie

    2. Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China

      Pengfei Cheng, Yifei Ren, Shunjie Bai, Yi Xu, Junxi Pan, Jin Chen, Meiling Liu & Peng Xie

    3. Department of Histology and Embryology, School of Basic Medicine of Jiamusi University, Jiamusi, 154002, Heilongjiang, China

      Pengfei Cheng

    4. Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China

      Shunjie Bai, Yu Wu & Junxi Pan

    5. Institute of Neuroscience, Jiamusi University, Jiamusi, 154002, Heilongjiang, China

      Xiaofeng Zhu

    6. Department of Neurology, The First Affiliated Hospital of Jiamusi University, Jiamusi, 154002, Heilongjiang, China

      Zhiguo Qi

    7. Department of Respiratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

      Weihua Shao

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

      Weiju Tang & Wen Huang

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    1. Pengfei Cheng
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    Correspondence to Peng Xie or Wen Huang.

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    Pengfei Cheng, Yifei Ren, Shunjie Bai, Yu Wu, and Yi Xu have contributed equally to the manuscript.

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    Cheng, P., Ren, Y., Bai, S. et al. Chronic Cerebral Ischemia Induces Downregulation of A1 Adenosine Receptors During White Matter Damage in Adult Mice. Cell Mol Neurobiol 35, 1149–1156 (2015). https://doi.org/10.1007/s10571-015-0208-4

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