TOXICOLOGY AND INDUSTRIAL HEALTH
·
2024
·
IF 1.7
Yuxin Wang,Yi Guo,Jiajia Ren,Qiling Liu,Chong Wang
Earlier research has demonstrated that developmental exposure to bisphenol A (BPA) has persistent impacts on both adult brain growth and actions. It has been suggested that BPA might obstruct the methylation coding of the genes in the brain. In this study, the methylation changes in the hippocampus tissue of male rat pups were examined following prenatal BPA exposure. Pregnant Sprague-Dawley rats were treated with either vehicle (tocopherol-stripped corn oil) or BPA (4, 40, or 400 μg/kg·body weight/day) throughout the entire duration of gestation and lactation. At 3 weeks of age, the male rat offspring were euthanized, and the hippocampus were dissected out for analysis. The expression levels of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) and DNA demethylases (TET1, Gadd45a, Gadd45b, and Apobec1) were analyzed in the hippocampus by means of quantitative real-time polymerase chain reaction and Western blotting, respectively. The results showed that prenatal exposure to BPA upregulated the expression of enzymes associated with DNA methylation and demethylation processes in the hippocampus of male rat offspring. These findings suggest that prenatal exposure to a low dose of BPA could potentially disrupt the balance of methylation and demethylation in the hippocampus, thereby perturbing epigenetic modifications. This may represent a neurotoxicity mechanism of BPA.
研究领域:
神经科学
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表观遗传学
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毒理学
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DOI
PubMed
高影响因子
BIOSCIENCE REPORTS
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2020
·Vol. 40
·期 8
·
IF 2.942
Zhu Jialei,Tang Jing
Postpartum depression (PPD) is a kind of mental disorder characterized by persistent low emotions in puerperium. The most significant physiological change in postpartum is lactation which is regulated by oxytocin receptor (OXTR). However, whether OXTR is related to pathological process of PPD and the potential mechanism still remain unclear. In the present study, we prepared hormone-simulated pregnancy (HSP)-induced PPD mouse model and found that the protein level of OXTR in hippocampus of PPD model mice was down-regulated and Nod-like receptor protein 3 (NLRP3) inflammasome was activated. We identified five long non-coding RNAs (lncRNAs) related to PPD by transcriptome sequencing, including three up-regulated and two down-regulated. The five lncRNAs were associated with the signaling pathway of OXTR according to the bioinformatics analysis. Furthermore, we focused on one of the five lncRNAs, Gm14205, and found that it targeted OXTR which inhibited astrocytic NLRP3 inflammasome activation in hippocampal primary astrocytes. These findings illustrate that OXTR has protective effects in PPD by inhibiting NLRP3 inflammasome activation and provides a new strategy for targeting lncRNA Gm14205 in the pathogenesis of PPD.
研究领域:
神经科学
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分子生物学
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药理学
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精神病学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND INDUSTRIAL HEALTH
·
2021
·
IF 2.273
Chong Wang,Yao Shu,Li Xu,Qiling Liu,Bei Zhang,Hong Zhang
Bisphenol A (BPA), a component of polycarbonate and epoxy resins, has been reported to induce learning and memory deficits. However, the mechanisms have not been fully elucidated. Growing evidence has suggested that N-methyl-d-aspartate receptors (NMDARs) are involved in cognitive impairments. In this study, BPA was administered to female Sprague–Dawley rats (six per dose group) at concentrations of 0 (control), 4, 40, and 400 μg/kg·body weight/day from gestation day 1 through lactation day 21. Spatial learning was evaluated using the Morris water maze on postnatal day 22. Expression levels of NMDARs were determined using real-time polymerase chain reaction and Western blot. The results showed that male offspring exposed to BPA exhibited increased latency in reaching the platform and reduced time in the target quadrant, and the number of crossing the platform was less, as compared with the control group. The mRNA and protein expression levels of NMDARs in the hippocampus were significantly downregulated when compared with the control group of male offspring. The data showed that maternal exposure to BPA at low dosage can cause cognitive deficits in male rat offspring, probably due to a decrease in NMDARs in the hippocampus.
研究领域:
神经科学
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毒理学
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发育生物学
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DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2018
·Vol. 32
·期 11
·e4338
·
IF 1.688
Dan Huang,Qing-Song Jiang,Jun-Qing Yang,Ting Cui,Nian-Ru Wang,Ting-Ting Du,Xin-Hui Jiang
The determination of amino acids and monoamine with actions like neurotransmitters or modulators has become increasingly important for studying the relationship between the dysfunction of neurotransmitters and the pathogenesis of diabetic encephalopathy. Here, a high-performance liquid chromatography with fluorescence detection method was developed to simultaneously determine nine monoamines and amino acids including three excitatory neurotransmitters (aspartate, glutamate, and serotonin), four inhibitory neurotransmitters (glycine, γ -aminobutyric acid, taurine, dopamine), a precursor of 5-HT (tryptophan) and methionine using homoserine as the internal standard. The separation was performed on a BDS column with methanol-buffer solution of 35 mmol/L sodium acetate and 5 mmol/L citric acid (pH 6.0) using a simple gradient elution. Several parameters including specificity, precision, and recovery were validated after optimization of the analytical conditions. The developed method was successfully applied to determine the cortex and the hippocampus samples from Sprague–Dawley rats. Our results showed that various neurotransmitters involved in diabetes mellitus may tend to be differentially modulated and present a different alteration tendency at different time course, which might be associated with the duration of diabetes mellitus.
研究领域:
神经科学
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药理学
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分析化学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2022
·
IF 6.117
Huawu Gao,Xin Lei,Shu Ye,Ting Ye,Rupeng Hua,Guoquan Wang,Hang Song,Peng Zhou,Yan Wang,Biao Cai
Genistein (GS), an isoflavone compound found in soybean, plays a neuroprotective role in Alzheimer's disease (AD). However, the mechanism of its action remains unclear. Herein, binding ability between GS and GRP78 was predicted by molecular docking , and the effect of GS in vivo and vitro were further studied. In this study, the effects of GS on learning and memory ability, changes of hippocampal neurons and ultrastructure of hippocampal CA3 region in AD rats were investigated. Besides, the protein or mRNA levels of the related proteins were detected. The results showed GS could effectively improve the learning and the memory ability, reduce the damage of hippocampal neurons, and decrease the protein or mRNA expression levels of GRP78, CHOP, Caspase-12, Cle-Caspase-9, Cle-Caspase-3, PERK, and p-PERK. Taken together, our data reveal GS has a neuroprotective effect by inhibiting the ERS-mediated apoptotic pathway, which may be a new therapeutic target for the treatment of AD .
研究领域:
神经科学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2024
·
IF 4.2
Tingting Wang,Xia Wu,Xiaoli Zhao,Jiaqi Li,Jian Yu,Maozheng Sheng,Mingyuan Gao,Yutang Cao,Jiawen Wang,Xiaozhen Guo,Kai Zeng
Purpose Postoperative cognitive dysfunction (POCD) is a central nervous system complication that occurs after anesthesia, particularly among the elderly. However, the neurological pathogenesis of postoperative cognitive dysfunction remains unclear. The aim of this study was to evaluate the effects of sevoflurane exposure on serum metabolites and hippocampal gene expression in elderly patients and aging mice by metabolomics and transcriptomic analysis and to explore the pathogenesis of sevoflurane induced POCD.Patients and Methods Human serum samples from five patients over 60 years old were collected before sevoflurane anesthesia and 1 hour after anesthesia. Besides, mice aged at 12 months (n=6 per group) were anesthetized with sevoflurane for 2 hours or with sham procedure. Subsequently, serum and hippocampal tissues were harvested for analysis. Further investigation into the relationship between isatin and neuroinflammation was conducted using BV2 microglial cells.Results Sevoflurane anesthesia led to the activation of inflammatory pathways, an increased presence of hippocampal astrocytes and microglia, and elevated expression of neuroinflammatory cytokines. Comparative analysis identified 12 differential metabolites that exhibited changes in both human and mouse serum post-sevoflurane anesthesia. Notably, isatin levels were significantly decreased after anesthesia. Notably, isatin levels significantly decreased after anesthesia, a factor known to stimulate proliferation and proinflammatory gene expression in microglia—the pivotal cell type in inflammatory responses.Conclusion Sevoflurane-induced alterations in serum metabolites in both elderly patients and aging mice, subsequently contributing to increased inflammation in the hippocampus.
研究领域:
麻醉学
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神经科学
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老年医学
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药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Pengfei Yan,Junchao Wang,Xiyu Zhao,Liangyu Wang,Jia Xu,Weijia Li,Weihong Min,Dan Wu,Chunlei Liu
QMDDQ is peptide derived from shrimp that ameliorates scopolamine-induced memory impairment. In this study, behavioral experiments in mice showed that QMDDQ could reduce the latency, number of working memory errors of the total distance moved, number of reference memory errors, number of traversals of the original platform, and escape latency in mice. QMDDQ decreased AChE vitality and increased ACh, DA, and 5-HT content. HE staining revealed that the cells in the hippocampal areas exhibited a tight tissue structure, neat arrangement, clear outline, and no cell necrosis in the QMDDQ group. Immunohistochemistry showed that, the expression level of Notch1 protein was reduced, and that of the antibody antigen complex was reduced in the QMDDQ group. Immunofluorescence staining showed a decrease in the number of GFAP and Iba-1 of QMDDQ group. TEM revealed that the mitochondrial cristae are intact and clear of QMDDQ group. QMDDQ decreased expression levels of Notch 1, STAT3, HES1, GFAP, and Iba-1 and activated Notch1 signaling via western-blotting. Pharmacokinetic studies have shown that QMDDQ can be stably absorbed into the bloodstream, with absorption occurring within 12 h and metabolism being completed within 24 h. This study establishes a theoretical basis for active peptides to ameliorate memory impairment and initiates the development of memory-enhancing functional foods.
研究领域:
神经科学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2017
·Vol. 32
·期 3
·e4114
·
IF 1.613
Hongli Du,Hai Zhang,Yahong Zhao,Min Liu,Anni Chen,Shiyu Liu,Dan Xue,Yanjun Liu,Guoqing Zhang
In recent years, vascular depression has become the focus of international attention. Yangxinshi Tablet (YXST) is usually used in cthe linic for the treatment of arrhythmia and heart failure, but we found that it also has antidepressive effects. The objective of the study was to identify biomarkers related to vascular depression in hippocampus and explore the antidepressive effects of YXST on the mouse model. Untargeted metabolomics based on UHPLC-Q-TOF/MS was applied to identify significantly differential biomarkers between the model group and control group. Unsupervised principal component analysis (PCA) was used to scan the tendency of groups and partial least squares-discriminant analysis (PLS-DA) to distinguish between the vascular depressive mice and the sham. PCA stores showed clear differences in metabolism between the vascular depressive mice and sham groups. The PLS-DA model exhibited 38 metabolites as the biomarkers to distinguish the vascular depressive mice and the sham. Further, YXST significantly regulated 22 metabolites to normal levels. The results suggested that YXST has a comprehensive antidepressive effect on vascular depression via regulation of multiple metabolic pathways including amino acid, the tricarboxylic acid cycle and phosphoglyceride metabolisms. These findings provide insight into the pathophysiological mechanism underlying vascular depression and the mechanism of YXST.
研究领域:
药理学
·
神经科学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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