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Downregulation of Adhesion Molecule CHL1 in B Cells but Not T Cells of Patients with Major Depression and in the Brain of Mice with Chronic Stress

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Abstract

Depression is a common serious mental disorder with unclear pathogenesis. Currently, specific diagnostic biomarkers are yet to be characterized. The close homolog of L1 (CHL1) is a L1 family cell adhesion molecule involved in the regulation of neuronal survival and growth. Although genome-wide expression profiling of human lymphoblastoid cell lines (LCLs) reported neural cell adhesion molecule (NCAM) L1 as a tentative biomarker for selective serotonin reuptake inhibitor (SSRI) antidepressant response, the involvement of CHL1 in depression is unclear. In this study, using a well-established chronic unpredictable mild stress (CUMS) depression mouse model, we examined the mRNA and protein expression of CHL1 in normal control, CUMS, vehicle (VEH), fluoxetine (FLU), and clozapine (CLO) groups. We found that in the CUMS group, both mRNA and protein expression of CHL1 were downregulated in both the hippocampus and the cortex. Treatment of CUMS mice with FLU and CLO reversed CHL1 mRNA and protein expression. In the human study, we showed that CHL1 expression was significantly downregulated in monocytes of unipolar and bipolar depressive patients compared with healthy donors (HD) at both mRNA and protein levels. Consistently, ELISA showed that CHL1 levels in the serum of patients with depression were reduced and negatively correlated with their HRSD-21 scores. Further flow cytometry studies showed that the reduced number of CHL1 positive CD19+ and CD20+ B cells of patients with depression was subsequently reversed with antidepressant treatment. Our findings suggested that downregulation of CHL1 from both immune cells and the brain may be linked to the immunopathogenesis of depression. In conclusion, CHL1 may be an important predictive marker for both diagnosis and treatment outcome of depression.

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Funding

This research was supported by grant from the Science & Technology Development Fund of Tianjin Education Commission for Higher Education (2018KJ086), by the Youth Fund of the Second Hospital of Tianjin Medical University (2018ydey01) and by the MST grant (2011CB944200) to XFZ.

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Authors and Affiliations

  1. Department of Pathology, The Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China

    C. R. Yang

  2. School of Pharmacology and Medical Science, University of South Australia, Adelaide, 5000, Australia

    Xin-Fu Zhou

  3. Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, People’s Republic of China

    C. R. Yang, Q. Sun, H. P. Meng, S. Liu, X. H. Li, B. Zheng & Dong Ming

  4. Department of Clinical Laboratory, The Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China

    L. Ning

  5. Department of Stomatology, The Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China

    Z. Han

  6. Tianjin Mental Health Center, Tianjin, People’s Republic of China

    Y. Liu

  7. Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China

    W. Huang

  8. Faculty of Health Sciences, School of Medicine, University of Adelaide, Adelaide, 5000, Australia

    F. H. Zhou

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  1. C. R. Yang
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  2. L. Ning
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  3. F. H. Zhou
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  4. Q. Sun
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  9. S. Liu
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  10. X. H. Li
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  12. Dong Ming
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  13. Xin-Fu Zhou
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Correspondence to Dong Ming or Xin-Fu Zhou.

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All experiments were performed in accordance with the Animal Management Rules of the Ministry of Health of the People’s Republic of China. We declare that our study was carried out in accordance with the latest version of the Declaration of Helsinki. The Ethics Committee of Tianjin Mental Hospital approved all procedures (KY2018K015).

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Yang, C.R., Ning, L., Zhou, F.H. et al. Downregulation of Adhesion Molecule CHL1 in B Cells but Not T Cells of Patients with Major Depression and in the Brain of Mice with Chronic Stress. Neurotox Res 38, 914–928 (2020). https://doi.org/10.1007/s12640-020-00234-9

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