Points - Recent Research
Hypothalamic DNA Methylation in Rats with Dihydrotestosterone-Induced Polycystic Ovary Syndrome: Effects of Low-Frequency Electro-Acupuncture
Cytoprotective Effects of the Astragalus Membranaceus on Lipopolysaccharide Exposed Cells
The Effect of TCM Zhike-Houpu herbal pair (ZKHPHP) on Depressive Behaviors and Hippocampal Serotonin 1A Receptors in Rats Following Chronic Unpredictable Mild Stress (CUMS)

Hypothalamic DNA Methylation in Rats with Dihydrotestosterone-Induced Polycystic Ovary Syndrome: Effects of Low-Frequency Electro-Acupuncture

Cui P1, et al.

NEW FINDINGS: What is the central question of this study? What is the role of hypothalamic DNA methylation in the development of PCOS and the response to electro-acupuncture treatment. What is the main finding and its importance? Global DNA methylation and expression of DNA methyltransferases (Dnmts) were increased in PCOS-like rats, and electro-acupuncture decreased global DNA methylation and Dnmt3b expression. Pyrosequencing showed that the DNA methylation of some PCOS candidate genes was changed in the PCOS and PCOS+EA groups, suggesting that hypothalamic DNA methylation plays an important role in the development of PCOS and in mediating the effects of electro-acupuncture treatment.
ABSTRACT: Polycystic ovary syndrome (PCOS) is a common reproductive and endocrine disease of unknown etiology. Recently, epigenetic studies focusing on DNA methylation in PCOS have received much attention, but the mechanisms are still unclear. In the present study, we used the 5a-dihydrotestosterone-induced PCOS-like rat model and treated the rats with electro-acupuncture (EA). Rats were randomly divided into four groups - controls, diet-induced obesity (DIO), PCOS, and PCOS+EA. We examined the reproductive, metabolic, and behavioral phenotypes, validated the effect of EA, and explored the role of hypothalamic DNA methylation by analyzing the methylation of global DNA and selected candidate genes. The PCOS rats presented with reproductive dysfunctions such as lack of regular estrus cyclicity, metabolic disorders such as increased body weight and insulin resistance, and depression and anxiety-like behaviors. EA improved the reproductive functions, decreased body weight, and improved experimental depressive behavior. Furthermore, global DNA methylation and the expression of DNA methyltransferases (Dnmts) were increased in PCOS rats compared to the control group, and EA decreased the global DNA methylation and the expression of Dnmt3b. In addition, pyrosequencing showed that the DNA methylation of certain CpG sites in targeted genes (Plcg1, Camk2b, Esr2, and Pgr) was increased in the PCOS group, but the DNA methylation of Camk2b and Ar was decreased after EA treatment. These results indicate that hypothalamic DNA methylation might be correlated with the development of PCOS and that EA has an effect on hypothalamic DNA methylation in PCOS rats.

Exp Physiol. 2018 Sep 11. doi: 10.1113/EP087163. [Epub ahead of print]

Source: PubMed

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Cytoprotective Effects of the Astragalus Membranaceus on Lipopolysaccharide-Exposed Cells

Wu X1, et al.

NEW FINDINGS: What is the central question of this study? What is the role of hypothalamic DNA methylation in the development of PCOS and the response to electro-acupuncture treatment. What is the main finding and its importance? Global DNA methylation and expression of DNA methyltransferases (Dnmts) were increased in PCOS-like rats, and electro-acupuncture decreased global DNA methylation and Dnmt3b expression. Pyrosequencing showed that the DNA methylation of some PCOS candidate genes was changed in the PCOS and PCOS+EA groups, suggesting that hypothalamic DNA methylation plays an important role in the development of PCOS and in mediating the effects of electro-acupuncture treatment.
ABSTRACT: Polycystic ovary syndrome (PCOS) is a common reproductive and endocrine disease of unknown etiology. Recently, epigenetic studies focusing on DNA methylation in PCOS have received much attention, but the mechanisms are still unclear. In the present study, we used the 5a-dihydrotestosterone-induced PCOS-like rat model and treated the rats with electro-acupuncture (EA). Rats were randomly divided into four groups - controls, diet-induced obesity (DIO), PCOS, and PCOS+EA. We examined the reproductive, metabolic, and behavioral phenotypes, validated the effect of EA, and explored the role of hypothalamic DNA methylation by analyzing the methylation of global DNA and selected candidate genes. The PCOS rats presented with reproductive dysfunctions such as lack of regular estrus cyclicity, metabolic disorders such as increased body weight and insulin resistance, and depression and anxiety-like behaviors. EA improved the reproductive functions, decreased body weight, and improved experimental depressive behavior. Furthermore, global DNA methylation and the expression of DNA methyltransferases (Dnmts) were increased in PCOS rats compared to the control group, and EA decreased the global DNA methylation and the expression of Dnmt3b. In addition, pyrosequencing showed that the DNA methylation of certain CpG sites in targeted genes (Plcg1, Camk2b, Esr2, and Pgr) was increased in the PCOS group, but the DNA methylation of Camk2b and Ar was decreased after EA treatment. These results indicate that hypothalamic DNA methylation might be correlated with the development of PCOS and that EA has an effect on hypothalamic DNA methylation in PCOS ratsAstragalus membranaceus (AM) is a traditional Chinese medicinal herb, whose cytoprotective effects remain largely unknown. Here, the bacterial endotoxin lipopolysaccharide (LPS) was applied to a human pulmonary type IIlike epithelial lung adenocarcinoma cell line, a human umbilical vein endothelial cell line, and a human bladder carcinoma cell line to construct in vitro models of intracellular oxidative stress. The authors assayed the cellular and mitochondrial cytoprotective effects of varying doses of AM root extract upon these cell lines. The cell lines were cultured as follows: LPS;only group, four LPS+AM groups treated with various AM concentrations plus LPS, and an untreated control group. Flow cytometry was used to assess apoptosis and cell cycle progression. A 2',7'dichlorofluorescein;diacetate assay was used to quantitate reactive oxygen species (ROS) generation. Mitochondrial membrane potential was analyzed by Rhodamine 123 assay. Western blotting was performed to detect cleaved caspase3, p53, and B cell lymphoma (Bcl);2 levels. Across all cell lines, LPS significantly elevated apoptosis rates, shifted cells to S/G2 phase, increased ROS production, reduced, upregulated cleaved caspase3, upregulated p53, and downregulated Bcl9;2 relative to controls (all P<0.05). As a general trend, increasing AM concentrations produced progressively greater reductions in the apoptosis rate, greater reductions in S/G2 phase %, greater reductions in ROS production, greater increases in, greater reductions in cleaved caspase and p53 expression, and greater increases in Bcl2 expression. AM treatment protects human pulmonary and bladder epithelial cells, in addition to human endothelial cells, from LPS;induced apoptosis, in a dose dependent manner..

Mol Med Rep. 2018 Sep 14. doi: 10.3892/mmr.2018.9483. [Epub ahead of print]

Source: PubMed

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The Effect of TCM Zhike-Houpu herbal pair (ZKHPHP) on Depressive Behaviors and Hippocampal Serotonin 1A Receptors in Rats Following Chronic Unpredictable Mild Stress (CUMS)

Xia Z1, et al.

OBJECTIVE: Zhike-Houpu herbal pair (ZKHPHP) is a well-known Chinese medicine to treat gastrointestinal motility dysfunction. Recently, many researchers have found that some of the compounds of ZKHPHP such as meranzin hydrate and magnolol have antidepressant effects. However, little is known about the antidepressant mechanism of ZKHPHP. Therefore, the main aim of the study is to evaluate the antidepressant-like effects of ZKHPHP and its possible mechanism of action on HTR1A (5-hydroxytryptamine receptor 1A) in the hippocampus CA1 region in rats exposed to chronic unpredictable mild stress.
METHODS: Male Sprague Dawley (SD) rats were randomly divided into six groups: Normal, Model, ZKHPHP(3g/kg), ZKHPHP(10g/kg), ZKHPHP(20g/kg) and ZKHPHP(30g/kg); N=8 per group. We exposed the rats to chronic unpredictable mild stress (CUMS) and then assessed antidepressant-like effects of ZKHPHP by measuring weight change, observing the open-field test and measuring sucrose water consumption. The antidepressant mechanism was examined by measuring the effect of ZKHPHP on HTR1A protein expression and HTR1A mRNA expression in the hippocampus CA1 region by using immunohistochemistry analysis, western blotting, and Real-time RT-PCR.
RESULTS: ZKHPHP (10 or 20g/kg) reduced the incidence of depressive-like behaviors and increased HTR1A protein and HTR1A mRNA expression in the hippocampus CA1 in rats displaying depressive behavior, while ZKHPHP (3 or 30g/kg) had no obvious effect on the measured depression indicators.
CONCLUSIONS: These data show that ZKHPHP has antidepressant-like effects based on a CUMS-induced depression model in rats. ZKHPHP may be attractive as an antidepressant because of its beneficial effects on depression and the absence of gastrointestinal dysregulation, which is a frequently observed unintended effect of many commonly used antidepressive medications.

Psychosom Med. 2018 Sep 13. doi: 10.1097/PSY.0000000000000639. [Epub ahead of print]

Source: PubMed

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