School of Pharmacy, Anhui Medical University, Hefei, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Hefei, China; The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China.
School of Pharmacy, Anhui Medical University, Hefei, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Hefei, China; The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China.
J Affect Disord. 2020 Sep 1;274:144-158. doi: 10.1016/j.jad.2020.05.017. Epub 2020 May 24.
Increasing evidence has shown the important role of exosomes in the maintenance of brain function and pathogenesis of brain disease, but little is known about their association with depression. The aim of this project was to explore the miRNA profile of exosomes in the serum of rats with depression induced by chronic unpredictable mild stress (CUMS).
A rat model of depression was replicated via CUMS. Behavioral performance was observed, and serum exosomes were isolated and identified. The protein expression levels of brain-derived neurotrophic factor (BDNF), TrkB, and synaptotagmin 1 in the hippocampus, prefrontal cortex (PFC), and serum exosomes were measured. GO and KEGG enrichment analysis of differential genes was carried out using the R package clusterProfiler.
The CUMS rats showed depression-like behaviors, together with decreased expression levels of BDNF, TrkB, and synaptotagmin 1 in the hippocampus, PFC, and serum exosomes. GO and KEGG enrichment analysis indicated that the differential expression of miRNAs might play an important role in the pathogenesis of stress-induced depression through the MAPK pathway, Wnt pathway, and mTOR pathway.
The protein expression levels of BDNF, TrkB, and synaptotagmin 1 were measured only in the hippocampus and PFC. The function of the differentially expressed miRNAs was not verified in the animal model, which should be investigated in detail in future studies.
The miRNA profile was altered in rats with stress-induced depression, which might be considered a potential biomarker for the early diagnosis of depression.
越来越多的证据表明外泌体在维持大脑功能和脑部疾病发病机制中的重要作用，但它们与抑郁症的关系知之甚少。本项目旨在探讨慢性不可预测轻度应激（CUMS）诱导的抑郁大鼠血清中外泌体的 miRNA 谱。
通过 CUMS 复制大鼠抑郁模型。观察行为表现，分离并鉴定血清外泌体。测量海马、前额叶皮质（PFC）和血清外泌体中脑源性神经营养因子（BDNF）、TrkB 和突触结合蛋白 1 的蛋白表达水平。使用 R 包 clusterProfiler 对差异基因进行 GO 和 KEGG 富集分析。
CUMS 大鼠表现出抑郁样行为，同时海马、PFC 和血清外泌体中 BDNF、TrkB 和突触结合蛋白 1 的表达水平降低。GO 和 KEGG 富集分析表明，差异表达的 miRNAs 可能通过 MAPK 通路、Wnt 通路和 mTOR 通路在应激诱导的抑郁症发病机制中发挥重要作用。
BDNF、TrkB 和突触结合蛋白 1 的蛋白表达水平仅在海马和 PFC 中进行了测量。动物模型中未验证差异表达 miRNAs 的功能，这应在未来的研究中进行详细研究。
应激诱导的抑郁大鼠的 miRNA 谱发生改变，这可能被认为是早期诊断抑郁症的潜在生物标志物。
