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Chronic restraint stress–induced depression-like behavior is mediated by upregulation of melanopsin expression in C57BL/6 mice retina

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Abstract

Background

Depression is associated with circadian disturbances in which melanopsin was a key mechanism. Further studies have demonstrated that melanopsin gene variations are associated with some depressive disorders and aberrant light can impair mood through melanopsin-expressing retinal ganglion cells (mRGCs). The goal of this study was to explore the direct relationship between depression and melanopsin.

Methods

Adult C57BL/6 male mice were physically restrained for 16 h in a 50-ml polypropylene centrifuge tube and all behavioral tests were performed after CRS treatment. Western blot analysis and immunofluorescence were used to detect melanopsin expression in the retina of C57BL/6 mice. And we observed the change of the electrophysiological function and release of glutamate of mRGCs.

Results

The melanopsin expression upregulate in mRGCs of chronic restraint stress (CRS)-treating mice which exhibit depression-like behavior. The frequency of blue light-induced action potentials and light-induced glutamate release mediated by melanopsin also increase significantly. This change of melanopsin is mediated by the CRS-induced glucocorticoid.

Conclusions

CRS may induce the depression-like behavior in mice via glucocorticoid-melanopsin pathway. Our findings provide a novel mechanistic link between CRS-induced depression and melanopsin in mice.

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Funding

This work was supported by the Natural Science Foundation of Shanghai (20ZR1448400, 21ZR1455100 and 22ZR1453900), Science and Technology Innovation 2030-Major Project (2021ZD0203501 to Jiamin Xu), Shanghai “Science and Technology Innovation Action Plan” medical innovation research (21Y11905600), and the National Nature Science Foundation of China (81371491).

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Author notes

  1. Yingmei Fu, Shanshan Liu, and Yigang Dong are co-first authors.

Authors and Affiliations

  1. Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Yingmei Fu, Hongmei Liu, Qingqing Xu, Ruixue Yuan, Ailing Ning, Yanmin Peng & Shunying Yu

  2. Department of Anesthesiology, Nanjing Drum Tower Hospital, Nanjing, China

    Shanshan Liu

  3. Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, School of Physical Education & Health Care, East China Normal University, Shanghai, 200241, China

    Yigang Dong & Yixia Gan

  4. Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Xiaoyun Guo & Wu Hong

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  1. Yingmei Fu
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Fu, Y., Liu, S., Dong, Y. et al. Chronic restraint stress–induced depression-like behavior is mediated by upregulation of melanopsin expression in C57BL/6 mice retina. Psychopharmacology 240, 283–293 (2023). https://doi.org/10.1007/s00213-022-06302-6

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