BIOLOGICAL TRACE ELEMENT RESEARCH
·
2023
·
IF 3.9
Yan Nan,Wang Zhengdong,Li Zhou,Zheng Yang,Chang Nan,Xu Kangjie,Wang Qian,Duan Xiaoxu
This study aimed to examine the immuntoxic effects of arsenic in the nervous system. Our results showed that arsenic increased corticocerebral and hippocampal weights ( p < 0.05). Morris water maze tests revealed that arsenic significantly increased the time spent in latency to platform on the fourth day in 50 mg/L arsenic exposure and the fifth day in 25 and 50 mg/L arsenic exposure, as well as reduced the path length in target quadrant, time spent in target quadrant, and crossing times of the platform ( p < 0.05). Hematoxylin–eosin staining showed that the vacuolated degeneration and pyknosis was found in the cerebral cortex and hippocampus of arsenic-treated mice. The mRNA levels of corticocerebral and hippocampal brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were decreased in the 50 mg/L arsenic-treated group ( p < 0.05). In addition, immunofluorescence staining showed that 25 and 50 mg/L arsenic all increased the expression of CD11b and glial fibrillary acidic protein (GFAP) in the cerebral cortex and hippocampus ( p < 0.05). Arsenic markedly raised antigen-presenting molecule MHCII and CD40 mRNA levels in the cerebral cortex and hippocampus and upregulated the cell chemokine receptor 5 (CCR5) and CCR7 mRNA levels in the cerebral cortex at the 50 mg/L arsenic group, and increased the CCR7 mRNA levels in the hippocampus at the 25 and 50 mg/L arsenic groups ( p < 0.05). Arsenic activated the nucleotide-binding domain-like receptor protein-3 (NLRP3) inflammasome, and enhanced its upstream promoter NF-κB protein level and downstream regulators IL-18 mRNA levels. Collectively, these results provide new evidences for the neuro-immune toxicity of arsenic. Graphical abstract
研究领域:
神经毒理学
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免疫毒理学
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神经科学
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DOI
PubMed
高影响因子
Foods
·
2026
·Vol. 15
·期 9
·1535
·
IF 6
Fangling Feng,Shuo Zhang,Chencen Lai,Zhiyu Chen,Jian Zhang,Jiuming He,Min Zhang,Pengjiao Wang,Xiuli Gao
Depression is a common mental disorder that substantially impairs patients’ daily life and work. To identify natural and safe preventive options, we investigated the preventive effect and underlying mechanism of theGanoderma lucidumandRosa roxburghiiTratt formula (GLRRTF) on depression. A total of 72 chemical components in GLRRTF were identified by UHPLC-ESI-Q-Exactive Plus Orbitrap-MS Analysis. GLRRTF (containing 400 mg/kg ofG. lucidumextract and 800 mg/kg ofR. roxburghiiextract per day), administered as a 1-week preventive intervention followed by 4 weeks of co-administration with chronic unpredictable mild stress, prevented the development of depression-like behaviors in male C57BL/6J mice and reduced neuronal damage in the hippocampus. Airflow-assisted desorption electrospray ionization mass spectrometry imaging and enzyme-linked immunosorbent assays showed that GLRRTF corrected abnormalities in neurotransmitter levels. The 16S rRNA sequencing indicated that GLRRTF restored dysbiosis of the gut microbiota. Metabolomic profiling revealed that GLRRTF increased the level of tryptophan and promoted tryptophan metabolism towards the 5-HT and indole pathways in feces and the brain. Western blot demonstrated that GLRRTF increased 5-HT production from tryptophan in the brain by regulating tryptophan hydroxylase 2 and DOPA decarboxylase. GLRRTF activated the PI3K/AKT pathway by regulating brain-derived neurotrophic factor and its receptor tropomyosin receptor kinase B. This research provides a comprehensive mechanistic understanding of GLRRTF’s preventive effect against depression, highlighting its potential as a novel, safe, and preventive functional food formulation.
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PubMed
高影响因子
EUROPEAN JOURNAL OF NEUROSCIENCE
·
2021
·Vol. 54
·期 6
·6304-6321
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IF 3.386
Jin Huang,Ya-Xin Tan,Lu-Lu Xue,Ruo-Lan Du,Jun-Jie Chen,Li Chen,Ting-Ting Li,Xue Bai,Si-Jin Yang,Liu-Lin Xiong,Ting-Hua Wang
Neonatal hypoxic–ischaemic (HI) injury is a serious complication of neonatal asphyxia and the leading cause of neonatal acute death and chronic neurological injury, and the effective therapeutic method is lacking to improve patients' outcomes. We reported in this study that panax notoginseng saponin (PNS) may provide a treatment option for HI. HI model was established using neonatal Sprague–Dawley rats and then intraperitoneally injected with different dosage of PNS, once a day for 7 days. Histological staining and behavioural evaluations were performed to elucidate the pathological changes and neurobehavioural variation after PNS treatment. We found PNS administration significantly reduced the infarct volume of brain tissues and improved the autonomous activities of neonatal rats, especially with higher dosage. PNS treatment at 40 mg/kg reduced neuronal damage, suppressed neuronal apoptosis and depressed astroglial reactive response. Moreover, the long-term cognitive and motor functions were also improved after PNS treatment at 40 mg/kg. Importantly, PNS treatment elevated the levels of BDNF and TrkB but decreased the expression of p75NTR both in the cortex and hippocampus of HI rats. The therapeutic efficacy of PNS might be correlated with PNS-activated BDNF/TrkB signalling and inactivation of p75NTR expression, providing a novel potential therapy for alleviating HI injury.
研究领域:
神经科学
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药理学
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儿科
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DOI
PubMed
高影响因子
Science of Advanced Materials
·
2021
·Vol. 13
·期 5
·864-873
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IF 1.474
Chen Ping,Yue Xinai,Dai Wei,Wang Xia,Li Yingying,Xie Hongjian,Jiang Dongmei,Jiang Yongmei
N-acetyl-L-cysteine-modified CdTe QDs (Cadmium Telluride Quantum Dots) were obtained by hydrothermal method, and DA (amino deoxyglucose), PEG (polyethylene glycol), and 9-p-D (9 polyamine acid) were obtained by ligand substitution, which were used for remodifying CdTe
QDs. Successively, a novel CdTe QDs nanoma-terial, CdTe-NALC, was obtained. This composite nanometer material was characterized by ultraviolet, fluorescence spectrum, nuclear magnetic resonance hydrogen-spectrum, and other methods to study further its biocompatibility and toxic effect on the
primary cultured mouse hippocampus neurons. PC12 cells were vitro-cultured and dissolved in the CdTe-NALC solution with different concentrations. After 24 h, the expression levels of proteins related to the cAMP (cyclic adenosine monophosphate)-CREB (cAMP response element-binding proteins)-BDNF
(brain-derived neurotrophic factor) signaling pathway in the cells were detected by ELISA (enzyme-linked immunosorbent assay) kit. In the experiment, the DA/9-p-D/PEG-modified CdTe QDs composite nanometer material was successfully manufactured by ligand replacement. The nanoparticles
had good dis-persibility with an average particle size of about 9.2 nm. DA/9-p-D/PEG modification improved the biocompatibil-ity of the QDs. CdTe composite nanomaterials could significantly reduce the cell activity of mouse hippocampal neurons and promote their apoptosis, with an evident
dose-apoptosis relationship. With the increase of CDTE-NALC solution concentration, cAMP, pCREB (phosphorylated CREB), and BDNF protein content decreased (P < 0.05).
研究领域:
纳米技术
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神经科学
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细胞生物学
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生物化学
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DOI
高影响因子
METABOLIC BRAIN DISEASE
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2017
·Vol. 32
·期 3
·789-798
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IF 2.297
Wu Xiang,Chen Huixin,Huang Chunhui,Gu Xinmei,Wang Jialing,Xu Dilin,Yu Xin,Shuai Chu,Chen Liping,Li Shun,Xu Yiguo,Gao Tao,Ye Mingrui,Su Wei,Liu Haixiong,Zhang Jinrong,Wang Chuang,Chen Junping,Wang Qinwen,Cui Wei
Post-operative cognitive dysfunction (POCD) is associated with elderly patients undergoing surgery. However, pharmacological treatments for POCD are limited. In this study, we found that curcumin, an active compound derived from Curcuma longa , ameliorated the cognitive dysfunction following abdominal surgery in aged mice. Further, curcumin prevented surgery-induced anti-oxidant enzyme activity. Curcumin also increased brain-derived neurotrophic factor (BDNF)-positive area and expression of pAkt in the brain, suggesting that curcumin activated BDNF signaling in aged mice. Furthermore, curcumin neutralized cholinergic dysfunction involving choline acetyltransferase expression induced by surgery. These results strongly suggested that curcumin prevented cognitive impairments via multiple targets, possibly by increasing the activity of anti-oxidant enzymes, activation of BDNF signaling, and neutralization of cholinergic dysfunction, concurrently. Based on these novel findings, curcumin might be a potential agent in POCD prophylaxis and treatment.
研究领域:
神经科学
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药理学
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老年学
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DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
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2022
·Vol. 47
·期 12
·3761-3776
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IF 4.414
He Junhui,Li Dongmei,Wei Jie,Wang Sheng,Chu Shifeng,Zhang Zhao,He Fei,Wei Dongmei,Li Yi,Xie Jiaxiu,Lai Kedao,Chen Naihong,Wei Guining
Depression has become an important disease threatening human health. In recent years, the efficacy of Traditional Chinese Medicine (TCM) in treating the disease has become increasingly prominent, so it is meaningful to find new antidepressant TCM. Mahonia fortune (Lindl.) Fedde is a primary drug in traditional formulas for the treatment of depression, and alkaloids are the main components of it. However, the detailed mechanism of Mahonia alkaloids (MA) on depression remains unclear. This study aimed to investigate the effect of MA on gap junction function in depression via the miR-205/Cx43 axis. The antidepressant effects of MA were observed by a rat model of reserpine-induced depression and a model of corticosterone (CORT)-induced astrocytes. The concentrations of neurotransmitters were measured by ELISA, the expression of Connexin 43 (Cx43) protein was measured by Immunohistochemistry and western-blot, brain derived neurotrophic factor (BDNF), cAMP-response element binding protein (CREB) proteins were measured by western-blot, the pathological changes of prefrontal cortex were observed by hematoxylin–eosin (H&E) staining. Luciferase reporter assay was performed to verify the binding of miR-205 and Cx43. The regulation effect of Cx43 on CREB was verified by interference experiment. Gap junction dysfunction was detected by fluorescent yellow staining. The results confirmed that MA remarkably decreased miR-205 expression and increased Cx43, BDNF, CREB expression in depression rat and CORT-induced astrocytes. In addition, after overexpression of miR-205 in vitro, the decreased expression of Cx43, BDNF and CREB could be reversed by MA. Moreover, after interfering with Cx43, the decreased expression of CREB and BDNF could be reversed by MA. Thus, MA may ameliorate depressive behavior through CREB/BDNF pathway regulated by miR-205/Cx43 axis. Graphical Abstract
研究领域:
药理学
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神经科学
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分子生物学
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中药
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DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Zhiqiang Lu,Yuan Gao,Zhijie Bao,Songyi Lin
The peptide Ser-Phe-Gly-Asp-Ile (SFGDI), derived from sea cucumber, has demonstrated neuroprotective effects in cell models; however, the in vivo neuroprotective efficacy of SFGDI remains unexplored. In this study, we utilized a cognitive disorder mouse model induced by scopolamine and observed that daily oral administration of SFGDI at a dosage of 40 mg/kg resulted in improved behavioral performance in the Passive avoidance test, the Channel-type water maze test, and the Novel object recognition test (P < 0.05). Furthermore, our investigation into the underlying neuroprotective mechanisms of SFGDI revealed that it reduced oxidative stress levels through the activation of the Sirt3/SOD/ROS pathway, thereby balancing hippocampal unsaturated lipids (P < 0.05) in the mouse hippocampus. Moreover, SFGDI significantly decreased hippocampal neuroinflammation by modulating the activation of microglia and hypertrophy of astrocytes. Additionally, SFGDI was found to enhance synaptic plasticity in the mouse hippocampus by activating the ChAT/p-CaMKⅡ/BDNF pathway and increasing spine density in neuron cells (P < 0.05), particularly mushroom spines (P < 0.05). These experiments demonstrate that SFGDI exhibits neuroprotective effects by regulating hippocampal oxidative stress through the Sirt3/SOD/ROS pathway and synaptic plasticity via the ChAT/p-CaMKⅡ/BDNF pathway in the mouse hippocampus, thus emerging as a potential neuro-nutraceutical agent for alleviating memory impairment.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
高影响因子
Redox Biology
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2022
·
IF 10.787
Qian-Qian Han,Peng-Fei Wu,Yi-Heng Li,Yu Cao,Jian-Guo Chen,Fang Wang
Vitamin C, a key antioxidant in the central nervous system, cycles between ascorbic acid and dehydroascorbic acid under pathophysiological conditions. Clinical evidence supports that the absence of vitamin C may be linked to depressive symptoms, but much less is known about the mechanism. Herein, we show that chronic stress disrupts the expression of ascorbic acid transporter, sodium-dependent vitamin C transport 2, and induces a deficiency in endogenous ascorbic acid in the medial prefrontal cortex, leading to depressive-like behaviors by disturbing redox-dependent DNA methylation reprogramming. Attractively, ascorbic acid (100 mg/kg-1000 mg/kg, intraperitoneal injection, as bioequivalent of an intravenous drip dose of 0.48 g–4.8 g ascorbic acid per day in humans) produces rapid-acting antidepressant effects via triggering DNA demethylation catalyzed by ten-eleven translocation dioxygenases. In particular, the mechanistic studies by both transcriptome sequencing and methylation sequencing have shown that S100 calcium binding protein A4, a potentially protective factor against oxidative stress and brain injury, mediates the antidepressant activity of ascorbic acid via activating erb-b2 receptor tyrosine kinase 4 (ErbB4)-brain derived neurotrophic factor (BDNF) signaling pathway. Overall, our findings reveal a novel nutritional mechanism that couples stress to aberrant DNA methylation underlying depressive-like behaviors. Therefore, application of vitamin C may be a potential strategy for the treatment of depression.
研究领域:
神经科学
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药理学
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分子生物学
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精神病学
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产品关联
DOI
PubMed
高影响因子
Alexandria Engineering Journal
·
2024
·
IF 6.2
Huiyuan Peng,Weihua Guo,Jinsong Wang,Weili Xia,Yu Xiong,Wenhua Xu,Weibo Dai,Feng Zheng
Addressing the devastating and often irreversible effects of stroke necessitates innovative therapeutic strategies that go beyond the limitations of current treatments. This study heralds a promising interdisciplinary approach by employing LAP/PDA composite nanomaterials integrated into silk fibroin-based hydrogels. These engineered materials not only demonstrated significantly enhanced mechanical properties, but also showed excellent biocompatibility when co-cultured with human mesenchymal stem cells (hMSCs). Importantly, the application of these composite hydrogels in stroke models yielded remarkable therapeutic outcomes. The results indicated a substantial reduction in cerebral infarction volumes, improved survival rates of transplanted hMSCs, and increased neurogenesis, underlining their transformative potential in stroke management. Molecular markers such as AQP4, α-DG, and β-DG were also explored, revealing modulated astrocyte activation and cellular signaling pathways. In summary, the composite LAP/PDA nanomaterials, in conjunction with hMSCs and Brain-Derived Neurotrophic Factor (BDNF), unveil a compelling and multifaceted approach for addressing the unmet needs in stroke treatment, thereby opening new avenues in regenerative medicine and tissue engineering.
研究领域:
神经科学
·
再生医学
·
组织工程
·
纳米技术
·
干细胞生物学
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DOI
高影响因子
BRAIN BEHAVIOR AND IMMUNITY
·
2021
·
IF 7.217
Yun Wang,Ce Gao,Tianyu Gao,Lu Zhao,Shiguang Zhu,Lin Guo
A growing body of studies indicated that exosomes are one of vital players in pathological process of neuropsychiatric diseases, but their role in major depressive disorder (MDD) remains poorly understood. Here we purified plasma exosomes from depression including lipopolysaccharide (LPS)-challenged depression, chronic restraint stress (CRS)-induced depression, MDD subjects, and from control mice or volunteers. The therapeutic effect of these exogenous exosomes was assessed utilizing behavioral tests and biochemical approaches in the LPS-caused depression or microglial BV2 cells. The expression of exosomal sigma-1 receptor (Sig-1R) was evaluated by western blotting. The role of Sig-1R in the biological function of exosomes was determined using Sig-1R knockout mice and HEK 293 cells. Our results revealed that injection of exosomes from depression models or patients rather than normal controls significantly ameliorated depressive-like behaviors, deficiency of BDNF expression and neuro-inflammation in LPS-challenged mice. In addition, co-culture with exosomes from depression models or patients instead of from controls prevented LPS-induced inflammation responses in microglial BV2 cells. Moreover, Sig-1R was demonstrated for the first time to significantly be enriched in exosomes from depression models or patients compared with that from normal controls. However, Sig-1R null exosomes no longer emerged antidepressant-like action in LPS-challenged mice. Thus, we demonstrated that plasma exosomes from depression exerted antidepressant-like effects in a Sig-1R dependent manner in the LPS-induced depression. This work improves our understanding of the exosomes in depression, suggesting a novel exosomes-based approach for MDD treatment.
研究领域:
神经科学
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药理学
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分子生物学
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精神病学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2022
·Vol. 12
·期 9
·2202785
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IF 11.092
Jingzhi Xu,Kun Xi,Jincheng Tang,Juan Wang,Yunkai Tang,Liang Wu,Yichang Xu,Zonghan Xu,Liang Chen,Wenguo Cui,Yong Gu
Living biomaterials directly couple with live cells to synthesize functional molecules and respond to dynamic environments, allowing the design, construction and application of next generation composite materials. Improving the coordination and communication between artificial materials and living cells is essential. In this study, collagen self-assembly and micro-sol electrospinning techniques are used to prepare oriented living fiber bundles that can increase the transplantation rate of stem cells in the early stages of inflammation, indirectly enhancing the dynamic regulation of stem cells during inflammation. Additionally, brain-derived neurotrophic factor (BDNF) contained in the fiber can improve the differentiation of bone marrow mesenchymal stem cells (BMSCs) into neurons once the inflammatory storm subsides. The living oriented fiber bundles fully simulate the 3D structure of the central nervous system, activate integrin β 1, promote the growth and adhesion of stem cells in the acute stage of inflammation, upregulate anti-inflammatory genes by more than twofold via BMSCs in response to inflammation, and stably release BDNF for up to 4 weeks post-inflammation storm subsidence. Finally, the BDNF induces the differentiation of BMSCs to neurons by enhancing the expression of neural-related genes, which enables the recovery of neurological functions in the later stages of spinal cord injury.
研究领域:
生物医学工程
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组织工程
·
干细胞生物学
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神经科学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2021
·
IF 11.614
Ziru Yu,Dewen Kong,Yu Liang,Xiaoyue Zhao,Guanhua Du
Nicotinic α 4 β 2 receptor antagonists have drawn increasing attention in the development of new antidepressants. In this study, we aimed to investigate the protective effect of VMY-2-95, the new selective antagonist of α 4 β 2 nicotinic acetylcholine receptor (nAChR) on corticosterone (CORT) injured mice and cellular models. Fluoxetine was applied as a positive control, and the effects of VMY-2-95 were investigated with three different doses or concentrations (1, 3, 10 mg/kg in mice, and 0.003, 0.03, 0.1 μmol/L in cells). As a result, VMY-2-95 showed significant antidepressant-like effects in the CORT injured mice by improving neuromorphic function, promoting hippocampal nerve proliferation, and regulating the contents of monoamine transmitters. Meanwhile, VMY-2-95 exhibited protective effects on cell viability, cell oxidant, cell apoptosis, and mitochondrial energy metabolism on corticosterone-impaired SH-SY5Y cells. Also, the PKA–CREB–BDNF signaling pathway was up-regulated by VMY-2-95 both in vitro and in vivo , and pathway blockers were also combined with VMY-2-95 to verify the effects furtherly. Therefore, we preliminarily proved that VMY-2-95 had protective effects in depressed mice and SH-SY5Y cells against injuries induced by corticosterone. This work indicated that the application of VMY-2-95 is a potential pharmacological solution for depression. This study also supported the development of α 4 β 2 nAChR antagonists towards neuropsychiatric dysfunctions.
研究领域:
神经科学
·
药理学
·
分子生物学
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DOI
PubMed
高影响因子
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