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Involvement of purinergic P2Y1R in antidepressant-like effects of electroacupuncture treatment on social isolation stress mice

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Abstract

Depression is a common neuropsychiatric disorder with high incidence and disability. Electroacupuncture (EA) is effective in the treatment of depression. However, the underlying mechanisms are not fully understood. Social isolation stress during post-weaning period can impair purinergic signaling in the brain of rodents and has emerged as a major risk factor for depression. The purpose of this study was to investigate the involvement of P2Y1 receptor (P2Y1R) in the antidepressant-like effects of EA. In this study, C57BL/6 mice were randomly assigned to group-housed (GH) or social isolated (SI) groups at post-natal day 21. After 6 weeks of social isolation, EA was performed on acupoints “Bai-hui” (GV20) and “Yin-tang” (GV29), or non-acupoints for 4 weeks. The SI mice received either intracerebroventricular injection of a selective P2Y1R agonist, MRS2365 (1 nmol); or a selective P2Y1R antagonist, MRS2179 (2 μmol), before and after EA. We found that SI mice exhibited depression-like behaviors accompanied with anxiety-like behaviors. The expressions of P2Y1R were well co-localized with GFAP-positive astrocytes and increased in the prefrontal cortex and hippocampus of SI mice. After treated with MRS2179, the depression-like behaviors of SI mice were attenuated, but not with MRS2365. Meanwhile, we found that EA could attenuate social isolation caused depression- and anxiety-like behaviors, and inhibited the up-regulation of P2Y1R in the prefrontal cortex and hippocampus of SI mice. Notably, the positive effects of EA on depression-like behaviors of SI mice could be reversed by MRS2365, while MRS2365 had no effect on the anxiolytic-like effects of EA. Therefore, we provide new evidence that EA could ameliorate depression- and anxiety-like behaviors in social isolation stress mice, and P2Y1R was involved in the antidepressant-like effects of EA.

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Funding

This work was supported by National Natural Science Foundation of China (82174500, 82004491), China Postdoctoral Science Foundation (2017M612472), and Young Excellent Medical Scholarship of Hubei Province (2020 LJRC011).

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Authors and Affiliations

  1. Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, China

    Lingling Yu & Guang Chen

  2. Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Lingling Yu, Yao Wang, Jiahuan Hao & Minjie Xie

  3. Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Hong Zhang & Man Li

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  1. Lingling Yu
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  2. Yao Wang
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  5. Guang Chen
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Contributions

LY and MX designed the experiments. LY conducted the EA treatment and performed the experiments. JH and HZ performed the data analysis. LY wrote the manuscript. YW added the experimental data and GC mainly takes charge of checking format and grammar errors in the revised manuscript. All authors helped revise the manuscript and approved the final manuscript.

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Correspondence to Jiahuan Hao or Minjie Xie.

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The experimental procedure was approved by the Animal Ethics Committee of Tongji Hospital, Huazhong University of Science and Technology.

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Conflicts of interest

Lingling Yu declares that she has no conflict of interest.

Wang Yao declares that he has no conflict of interest.

Hong Zhang declares that he has no conflict of interest.

Man Li declares that she has no conflict of interest.

Chen Guang declares that he has no conflict of interest.

Jiahuan Hao declares that he has no conflict of interest.

Minjie Xie declares that she has no conflict of interest.

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Yu, L., Wang, Y., Zhang, H. et al. Involvement of purinergic P2Y1R in antidepressant-like effects of electroacupuncture treatment on social isolation stress mice. Purinergic Signalling 19, 55–68 (2023). https://doi.org/10.1007/s11302-021-09827-1

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