Involvement of proBDNF in Monocytes/Macrophages with Gastrointestinal Disorders in Depressive Mice
Involvement of proBDNF in Monocytes/Macrophages with Gastrointestinal Disorders in Depressive Mice
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proBDNF 参与抑郁小鼠胃肠道疾病的单核细胞/巨噬细胞
DOI：
10.1007/s12640-020-00235-8
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发表时间：
2020-06
影响因子：
3.7
通讯作者：
Dai Ru-Ping
中科院分区：
文献类型：
--
作者：
Yu Yun-Qing;Zhang Yan-Ling;Wang Zhe;Liu Yu;Li Hui;Zhou Xin-Fu;Hu Zhao-Lan;Dai Ru-Ping
重性抑郁症（MDD）通常与胃肠道（GI）疾病共病。脑源性神经营养因子前体（proBDNF）已被报道有助于小鼠模型中抑郁症的发展。然而，proBDNF在抑郁症相关的胃肠道疾病中的作用仍然未被揭示。小鼠经历不可预测的慢性轻度应激（UCMS）程序，然后腹膜内注射氟西汀（20 mg/kg）。采用旷场试验（OFT）、强迫游泳试验（FST）和蔗糖偏好试验（SPT）评定抑郁程度。进行口服食用染料凝胶和组织学染色以评估GI转运和形态学改变。进行QPCR以评估炎症细胞因子的mRNA水平。此外，流式细胞术，免疫组织化学和免疫荧光法进行检查的表达和细胞定位的proBDNF。结果发现：（a）抑郁症小鼠外周血中proBDNF及其受体p75 NTR在CD 11 B+细胞上的表达高于对照组，（B）UCMS手术后胃肠道运动减少，氟西汀治疗后胃肠道运动部分恢复，（c）proBDNF/p75 NTR在肠固有层巨噬细胞上高表达，（d）proBDNF/p75 NTR在肠固有层巨噬细胞上高表达，（e）proBDNF/p75 NTR在肠固有层巨噬细胞上高表达，（f）proBDNF/p75 NTR在肠固有层巨噬细胞上高表达。（4）proBDNF/p75 NTR的上调和IL-1 β、IL-6、IL-10、IFN-γ等细胞因子的激活与抑郁症和胃肠道疾病的发生呈正相关，氟西汀治疗可抑制其表达。UCMS程序上调了外周血单核/巨噬细胞和肠固有层中proBDNF和p75 NTR的表达，可能参与了抑郁症相关胃肠道疾病的发病机制。氟西汀逆转了抑郁小鼠的GI功能障碍、巨噬细胞浸润和proBDNF信号转导的上调。
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/p75NTRwas highly expressed in macrophages in the intestinal lamina propria; (d) the upregulated proBDNF/p75NTRand 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 p75NTRin 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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影响因子：
--
作者：
S. Hosseinzadeh;Sara Poorsaadati;Babak Radkani;M. Forootan
通讯作者：
S. Hosseinzadeh;Sara Poorsaadati;Babak Radkani;M. Forootan
ProBDNF 在单核细胞功能中的调节作用：对斯坦福 A 型主动脉夹层疾病的影响
影响因子：
4.8
作者：
Shen, Wei-Yun;Luo, Cong;Dai, Ru-Ping
通讯作者：
Dai, Ru-Ping
外周脑源性神经营养因子前体作为炎症介质调节疼痛
影响因子：
4.6
作者：
Luo C;Zhong XL;Zhou FH;Li JY;Zhou P;Xu JM;Song B;Li CQ;Zhou XF;Dai RP
通讯作者：
Dai RP
沉默 miR-150 可改善实验性自身免疫性脑脊髓炎
影响因子：
4.3
作者：
Hu Z;Cui Y;Qiao X;He X;Li F;Luo C;Wang S;Li C;Dai R
通讯作者：
Dai R
DOI：
10.1177/0269881117711708
发表时间：
2017-09
期刊：
Journal of psychopharmacology (Oxford, England)
影响因子：
--
作者：
Kopschina Feltes P;Doorduin J;Klein HC;Juárez-Orozco LE;Dierckx RA;Moriguchi-Jeckel CM;de Vries EF
通讯作者：
de Vries EF