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2.
J Affect Disord ; 274: 144-158, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32469797

RESUMO

BACKGROUND: 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). METHODS: 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. RESULTS: 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. LIMITATIONS: 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. CONCLUSIONS: The miRNA profile was altered in rats with stress-induced depression, which might be considered a potential biomarker for the early diagnosis of depression.


Assuntos
Exossomos , MicroRNAs , Animais , Antidepressivos , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/genética , Modelos Animais de Doenças , Exossomos/genética , Exossomos/metabolismo , Hipocampo/metabolismo , MicroRNAs/genética , Ratos , Estresse Psicológico/complicações , Estresse Psicológico/genética
3.
Front Pharmacol ; 10: 1544, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32009956

RESUMO

Quercetin is a polyphenol with multiple biological activities, and results of our preliminary study showed that it could shorten the immobility time of mice in the forced swimming test and tail suspending test. The aim of this study was to investigate its effects on the behavioral performance of lipopolysaccharide (LPS)-challenged rats and explore the potential mechanism. The results showed that intragastrical administration of quercetin (40 mg/kg) could improve the bodyweight gain of LPS-challenged rats, increase the saccharin preference index in the saccharin preference test and the novel arm preference index in the Y-maze, and decrease the immobility time in the FST. However, it showed no significant effect on the performance of LPS-challenged rats in the Morris water maze and the plasma concentrations of nesfatin-1, C-reactive protein (CRP), and IL-6. Results of western blot showed that the expression levels of BDNF, Copine 6, p-TrkB, and the triggering receptors expressed on myeloid cells (TREM) 1 were decreased in both the hippocampus and the prefrontal cortex (PFC) of LPS-challenged rats, while the expression of TREM2 was increased. The protein expression of synapsin-1 was decreased in the hippocampus without significant changes in the PFC. These imbalance protein expressions could be balanced by treatment with quercetin. The results suggested that quercetin could alleviate LPS-induced depression-like behaviors and impairment of learning and memory in rats, the mechanism of which might be involved with regulating the BDNF-related imbalance expression of Copine 6 and TREM1/2 in the hippocampus and the PFC.

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