Involvement of proBDNF in Monocytes/Macrophages with Gastrointestinal Disorders in Depressive Mice
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ORIGINAL ARTICLE
Involvement of proBDNF in Monocytes/Macrophages with Gastrointestinal Disorders in Depressive Mice Yun-Qing Yu 1,2 & Yan-Ling Zhang 1 & Zhe Wang 1 & Yu Liu 3 & Hui Li 1,2 & Xin-Fu Zhou 4 & Zhao-Lan Hu 1 & Ru-Ping Dai 1,2 Received: 19 January 2020 / Revised: 19 May 2020 / Accepted: 7 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Brain-derived neurotrophic factor precursor . Depression . Fluoxetine . Gastrointestinal disorders . Macrophage
Introduction
Yun-qing Yu and Yan-ling Zhang are co-first authors. Zhao-Lan Hu and Ru-Ping Dai contributed equally to this work. * Zhao-Lan Hu [email protected] * Ru-Ping Dai [email protected] 1
Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, China
2
Anesthesia Medical Research Center, Central South University, Changsha, China
3
Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, China
4
School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, Austr
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