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Involvement of proBDNF in Monocytes/Macrophages with Gastrointestinal Disorders in Depressive Mice

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A Correction to this article was published on 19 September 2020

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Abstract

Major depressive disorders (MDD) are often comorbid with the gastrointestinal (GI) disorders. Brain-derived neurotrophic factor precursor (proBDNF) has been reported to contribute to the development of depression in mouse models. However, the role of proBDNF in depression-associated GI disorders is still unrevealed. Mice experienced unpredictable chronic mild stress (UCMS) procedure and were then intraperitoneally injected with fluoxetine (20 mg/kg). Open field test (OFT), forced swimming test (FST), and sucrose preference test (SPT) were performed to evaluate the severity of depression. Oral administration of food dye gel and histological staining were performed to assess GI transit and morphological alterations. QPCR was performed to assess the mRNA levels of inflammatory cytokines. Additionally, flow cytometry, immunohistochemistry, and immunofluorescence were performed to examine the expression and cellular localization of proBDNF. It was found that (a) in the peripheral blood, the expression of proBDNF and its receptor pan neurotrophin receptor 75 (p75NTR) in CD11b+ cells in depressive mice was higher than in controls; (b) the GI motility was decreased after the UCMS procedure and partly reversed by fluoxetine treatment; (c) proBDNF/p75NTR was highly expressed in macrophages in the intestinal lamina propria; (d) the upregulated proBDNF/p75NTR and the activated cytokines, including IL (interleukin)-1β, IL-6, IL-10, and IFN (interferon)-γ, were positively correlated with the depression and GI disorders, and were inhibited by fluoxetine treatment. UCMS procedure upregulated the expression of proBDNF and p75NTR in monocytes/macrophages of peripheral blood and intestinal lamina propria, which may be involved in the pathogenesis of depression-associated GI disorders. Fluoxetine reversed the GI dysfunction, infiltration of macrophages, and upregulation of proBDNF signaling in the depressive mice.

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Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Change history

  • 19 September 2020

    Dr. Chang-Qi Li should be added as co-author because Fig. 1 originated from him.

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Acknowledgments

We thank Shanghai Yile Biotechnology Corp. for providing the biotin humanized monoclonal anti-proBDNF antibody.

Funding

This research was supported by National Natural Science Foundation of China (81771354 to RD, 81873770 to LH, and 81901231 to ZLH), and the Fundamental Research Funds for the Central Universities of Central South University (2019zzts812 to Yu YQ, 2019zzts1048 to Wang Z, and 506021710 to Liu Y).

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  1. Zhao-Lan Hu and Ru-Ping Dai contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, China

    Yun-Qing Yu, Yan-Ling Zhang, Zhe Wang, Hui Li, Zhao-Lan Hu & Ru-Ping Dai

  2. Anesthesia Medical Research Center, Central South University, Changsha, China

    Yun-Qing Yu, Hui Li & Ru-Ping Dai

  3. Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, China

    Yu Liu

  4. School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, Australia

    Xin-Fu Zhou

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Contributions

YY conducted the study, data collection, data analysis, and manuscript preparation; YZ conducted the study, data collection, and data analysis; ZW and YL helped do the animal-related experiments; HL helped design and analyze the data; XFZ provided reagents, interpreted data, and revised manuscripts; RD and ZH were responsible for designing and interpretation of the work, data collection, data analysis, and manuscript drafting; all authors had a final approval of the manuscript submission.

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Yu, YQ., Zhang, YL., Wang, Z. et al. Involvement of proBDNF in Monocytes/Macrophages with Gastrointestinal Disorders in Depressive Mice. Neurotox Res 38, 887–899 (2020). https://doi.org/10.1007/s12640-020-00235-8

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