SKF83959 Produces Antidepressant Effects in a Chronic Social Defeat Stress Model of Depression through BDNF-TrkB Pathway

Jiang, Bo; Wang, Fang; Yang, Shuxu; Peng, Fang; Deng, Zhifang; Xiao, Jun-Li; Hu, Zhuang-Li; Chen, Jianguo

doi:10.1093/ijnp/pyu096

Cited by 47 publications

(42 citation statements)

References 49 publications

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Section: Methodsmentioning

confidence: 99%

“…The dosages of these compounds were chosen according to previous reports. 12,15,16) For drug administration, intraperitoneally (i.p.) injected in a volume of 10 mL/kg was employed.…”

Section: Methodsmentioning

confidence: 99%

“…11) We noticed that in 2014, Jiang et al demonstrated the antidepressant effects of SKF83959 in mice which were mediated through activating the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) pathway. 12) It is wellknown that BDNF plays a very important role in synaptic plasticity, learning and memory. 13) Loss of BDNF function in the hippocampus and cortex leads to significant impairments in ability of memory.…”

Section: )mentioning

confidence: 99%

“…After denaturation, 30 µg of protein samples were loaded in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels and then transferred to polyvinylidene difluoride (PVDF) membranes. After that, the membranes were blocked in 5% bovine serum albumin (BSA) and then incubated in diluted various primary antibodies [as described in previous studies 12,15,16) ] overnight at 4°C. Next, the membranes were washed and incubated in diluted horseradish peroxidaseconjugated secondary antibodies (1: 5000) for 2 h at room temperature.…”

Section: Morris Water Mazementioning

confidence: 99%

“…The housing environment was set as described. 12,15,16) All the procedures involving mice were conducted in accordance with the Guide for the Care and Use of Laboratory Animals (8th edition, Institute of Laboratory Animal Resources on Life Sciences, National Research Council, National Academy of Sciences, Washington DC, U.S.A.), and approved by the Lab Animal Ethical Committee of Nantong University.Drugs and Treatments SKF83959 (0.5, 1 mg/kg; Tocris Bioscience, Bristol, U.K.), donepezil (5 mg/kg; Sigma, St. Louis, MO, U.S.A.), scopolamine (1 mg/kg; Sigma) and K252a (25 µg/kg; Alomone Laboratories, Jerusalem, Israel) were all dissolved in 1% dimethyl sulfoxide (DMSO) in 0.9% saline. The dosages of these compounds were chosen according to previous reports.…”

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confidence: 99%

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SKF83959 Has Protective Effects in the Scopolamine Model of Dementia

Sheng

Zhang

Gao

et al. 2018

Biological & Pharmaceutical Bulletin

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Patients with Alzheimer's disease (AD) always have cognitive impairments. In this study we investigated whether 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) has improvements on cognitive dysfunction. The scopolamine model of dementia was used to investigate the anti-amnesic activities of SKF83959, and then, Western blotting and pharmacological inhibitor were used to assay the anti-amnesic mechanisms of SKF83959. It was found that SKF83959 administration significantly improved the scopolamine-induced memory impairments in the passive avoidance task, Y-maze test, and Morris water maze task. Moreover, SKF83959 treatment significantly antagonized the down-regulating effects of scopolamine on brain-derived neurotrophic factor (BDNF) signaling cascade in the hippocampus, but not cortex. Importantly, the usage of K252a, a selective inhibitor of tyrosine kinase B (TrkB), significantly attenuated the protective effects of SKF83959 in the scopolamine model. Collectively, this study shows that SKF83959 has beneficial effects in the scopolamine model of dementia by modulation of hippocampal BDNF signaling, implying a novel and potential therapeutic agent for treating dementia in AD.Key words brain-derived neurotrophic factor; memory; scopolamine; SKF83959 As a world-wide neurodegenerative disease, Alzheimer's disease (AD) causes huge damage to our society.1) In clinical, patients with AD always have dementia, meaning the loss of memory.2,3) Dementia is very common in older persons, and leads to severe interference in occupational and social performance. Current researches have revealed that patients with AD have severe cholinergic dysfunction in the brain, [4][5][6] and some cholinergic antagonists, especially scopolamine, have been shown to induce memory impariments in rodents. 7) In contrast, some acetylcholinesterase inhibitors (AChEIs), such as donepezil, were developed for AD therapy in clinical. However, current AChEIs used clinically have various adverse effects including diarrhea, insomnia and vomiting, and their efficacy are not very good.8) Therefore, developing novel therapeutic agents to treat dementia in AD is very necessary.6-Chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) is one compound which belongs to benzazepine family and has been acknowledged as a selective D 1 -D 2 heteromer agonist. Until now, a lot of reports have been showing the effects of SKF83959 on the brain. For example, Wu et al. showed that SKF83959 has protective effects against neuroinflammation. 9)Chu et al. reported that SKF83959 has promoting effects on neuronal release of glutamate. 10) Zhang et al. found that SKF83959 administration has beneficial and reversing effects in the 6-hydroxy-dopamine (6-OHDA) model of Parkinson's disease. 11) We noticed that in 2014, Jiang et al. demonstrated the antidepressant effects of SKF83959 in mice which were mediated through activating the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (Tr...

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Section: Methodsmentioning

confidence: 99%

“…The dosages of these compounds were chosen according to previous reports. 12,15,16) For drug administration, intraperitoneally (i.p.) injected in a volume of 10 mL/kg was employed.…”

Section: Methodsmentioning

confidence: 99%

Section: )mentioning

confidence: 99%

Section: Morris Water Mazementioning

confidence: 99%

mentioning

confidence: 99%

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SKF83959 Has Protective Effects in the Scopolamine Model of Dementia

Sheng

Zhang

Gao

et al. 2018

Biological & Pharmaceutical Bulletin

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A comprehensive review of genetic and epigenetic mechanisms that regulate BDNF expression and function with relevance to major depressive disorder

Hing

Sathyaputri

Potash

2017

American J of Med Genetics Pt B

112

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Major depressive disorder (MDD) is a mood disorder that affects behavior and impairs cognition. A gene potentially important to this disorder is the brain derived neurotrophic factor (BDNF) as it is involved in processes controlling neuroplasticity. Various mechanisms exist to regulate BDNF's expression level, subcellular localization, and sorting to appropriate secretory pathways. Alterations to these processes by genetic factors and negative stressors can dysregulate its expression, with possible implications for MDD. Here, we review the mechanisms governing the regulation of BDNF expression, and discuss how disease-associated single nucleotide polymorphisms (SNPs) can alter these mechanisms, and influence MDD. As negative stressors increase the likelihood of MDD, we will also discuss the impact of these stressors on BDNF expression, the cellular effect of such a change, and its impact on behavior in animal models of stress. We will also describe epigenetic processes that mediate this change in BDNF expression. Similarities in BDNF expression between animal models of stress and those in MDD will be highlighted. We will also contrast epigenetic patterns at the BDNF locus between animal models of stress, and MDD patients, and address limitations to current clinical studies. Future work should focus on validating current genetic and epigenetic findings in tightly controlled clinical studies. Regions outside of BDNF promoters should also be explored, as should other epigenetic marks, to improve identification of biomarkers for MDD.

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The antidepressant‐like effects of Shen Yuan: Dependence on hippocampal BDNF–TrkB signaling activation in chronic social defeat depression‐like mice

Jiang

Huang

Wang

et al. 2021

Phytotherapy Research

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The aim of this paper is to elucidate the effects of SY treatment on chronic social defeat stress (CSDS)-induced depression-like symptoms and the related mechanism.Our results indicated that SY treatment reverses the depressive-like behaviors induced by CSDS as measured by the social interaction test, sucrose preference test, forced swim test, and tail suspension test. SY decreased the serum levels of CORT and increased hippocampal neurotransmitters (5-HT, DA, and NE) in CSDS mice.Meanwhile, SY upregulated the brain-derived neurotrophic factor (BDNF) signaling pathway and reversed the decreased hippocampal neurogenesis caused by CSDS. In addition, we found that the TrkB antagonist K252a fully blocked the SY effects on behavioral improvement and eliminated the promoting effects of SY on hippocampal neurogenesis and BDNF-TrkB signaling (including the downstream ERK and Akt pathways) activation, thus further demonstrating that BDNF-TrkB signaling was necessary for the SY effects. In conclusion, our study showed that SY acted as an antidepressant in mice exhibiting CSDS-induced depression-like symptoms, and its effect was facilitated by promoting hippocampal neurogenesis and BDNF signaling pathway activation.

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SKF83959 Produces Antidepressant Effects in a Chronic Social Defeat Stress Model of Depression through BDNF-TrkB Pathway

Cited by 47 publications

References 49 publications

SKF83959 Has Protective Effects in the Scopolamine Model of Dementia

SKF83959 Has Protective Effects in the Scopolamine Model of Dementia

A comprehensive review of genetic and epigenetic mechanisms that regulate BDNF expression and function with relevance to major depressive disorder

The antidepressant‐like effects of Shen Yuan: Dependence on hippocampal BDNF–TrkB signaling activation in chronic social defeat depression‐like mice

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