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Frontiers in Psychiatry · 2021 · IF 4.157

The Antidepressant-Like Effects of Shen Yuan in a Chronic Unpredictable Mild Stress Rat Model

Jiang Ning,Wang Haixia,Huang Hong,Lv Jingwei,Zeng Guirong,Wang Qiong,Bao Yu,Chen Ying,Liu Xinmin

Depression is a common yet severe neuropsychiatric condition that causes imposes considerable personal, economic, and social burdens worldwide. Medicinal plant species (e.g., Panax ginseng and Polygala tenuifolia) demonstrate potent antidepressant-like effects with less toxicity and other side effects. Shen yuan prescription (SY), composed of Panax ginseng (GT) and Polygala tenuifolia (YT). The present study aimed to elucidate the effects of SY treatment on chronic unpredictable mild stress (CUMS) rats and study the underlying mechanism. Our results indicated that SY (67.5, 135, or 270 mg/kg) significantly reverses the depressive-like behaviors in rats with a 5-week CUMS exposure, as demonstrated by increased sucrose consumption in the sucrose preference test, and decreased immobility time in the tail suspension and forced swim test. Moreover, SY altered serum corticosterone levels, pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), and oxidative markers (SOD, CAT, and MDA), and increased the levels of hippocampal neurotransmitters (5-HT, DA, and NE) in rats exposed to CUMS. Furthermore, rats treated with SY showed a reduction in the protein expression of BDNF, p-TrkB, p-Akt, and p-mTOR proteins induced by CUMS exposure in the hippocampus. In conclusion, SY prevented depressive-like behaviors in CUMS-exposed rats by preventing hypothalamus-pituitary-adrenal axis dysfunction, decreasing the levels of the neurotransmitters, minimizing oxidative stress, suppressing neuroinflammation, and activating the PI3K/Akt/mTOR-mediated BDNF/TrkB pathway, all of which are the key players in the pathological basis of depression.

CAS / MDL: 56296-78-7
研究领域: 神经精神病学 · 药理学 · 行为神经科学 · 分子生物学
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BRAIN RESEARCH BULLETIN · 2023 · IF 3.8

Exposure to enriched environment ameliorated chronic unpredictable mild stress-induced depression-like symptoms in rats via regulating the miR-92a-3p/kruppel-like factor 2 (KLF2) pathway

Xiao Ji,Zhenwu Zhao

Background Silencing of miR-92a-3p may be beneficial in relieving depression of chronically stressed rats. The level of kruppel-like factor 2 (KLF2) was increased in the striatum of depressed rats after ketamine treatment. Enriched environment (EE) ameliorated depression-like behaviors in rats. However, the specific mechanism of EE treatment on depression induced by chronic unpredictable mild stress (CUMS) remains unclear. Methods After CUMS-induced male Sprague Dawley rats were treated under EE or/and Adeno-Associated Virus (AAV)-miR-92a-3p, depression-like behaviors, cognitive ability, dendritic spine density, as well as levels of miR-92a-3p and KLF2 were detected by the behavioral tests, morris water maze test, Golgi staining, and quantitative real-time polymerase chain reaction (qRT-PCR) as needed. The body weight of rats was also measured. Next, primary hippocampal neurons were cultivated. The targeting relationship between miR-92a-3p and KLF2 was analyzed by TargetScan v7.2 and dual-luciferase reporter assay. After hippocampal neurons were transfected with miR-92a-3p mimic or/and overexpressed KLF2 vector, the cell viability, and apoptosis, together with the levels of KLF2, brain-derived neurotrophic factor (BDNF), phosphorylated (p)-tropomysin related kinase B (p-TrkB) and TrkB were determined by MTT assay, flow cytometry, qRT-PCR, and western blot as needed. Results EE ameliorated CUMS-induced depression-like behaviors and cognitive ability, and elevated the neuronal dendritic spine density and KLF2 level, but reduced miR-92a-3p level in hippocampal tissues, while the above effects were reversed by AAV-miR-92a-3p. MiR-92a-3p mimic restrained cell viability, along with p-TrkB/ TrkB and BDNF levels, but promoted apoptosis in hippocampal neurons, which were reversed by overexpressed KLF2. Conclusion EE ameliorates CUMS-induced depression-like symptoms in rats via regulating the miR-92a-3p/KLF2 pathway.

CAS / MDL: 64-17-5
研究领域: 神经科学 · 分子生物学 · 行为科学 · 药理学
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