Food & Function
·
2019
·Vol. 10
·期 9
·6009-6019
·
IF 3.241
Yun Yu,Xiu-Yuan Lang,Xi-Xi Li,Run-Ze Gu,Qing-Shan Liu,Rongfeng Lan,Xiao-Yan Qin
The major bioactive ingredient THSG of Polygonum multiflorum is well established for its anti-oxidation, anti-aging and anti-inflammation properties. Increasing evidence supports the capacity of THSG to ameliorate the biochemistry of neurotrophins and their downstream signaling axis in mouse models to attenuate neurodegenerative diseases such as Alzheimer's and Parkinson's disease. In this study, the neuroprotective effects of THSG were studied in vitro and in vivo. In cultured mesencephalic dopamine neurons and SH-SY5Y cell line, it was found that THSG protected the integrity of the cell body and neurite branching from MPP+-induced toxicity by restoring the expression of FGF2 and BDNF and their downstream signaling pathways to inhibit apoptosis and promote cell survival. The inhibition of Akt signaling by LY294002 or TrkB activity by K252a eliminated the neuroprotective effects of THSG. In the MPTP-induced mouse models of Parkinson's disease, THSG ameliorated the animal behaviors against MPTP-induced neurotoxicity, which was demonstrated by the pole test and the tail suspension test. Biochemical and immunohistochemical analysis verified the THSG-mediated restoration of the FGF2-Akt and BDNF-TrkB signaling axis in the substantia nigra and corpus striatum and the recovery of dopaminergic neurons. These results establish the neuroprotective effects of THSG in vitro and in vivo and unravel the underlying mechanism against toxin-induced neural atrophy, providing a new avenue for the use and pharmacological research of edible medicine for anti-neurodegenerative diseases.
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高影响因子
Science of Advanced Materials
·
2021
·Vol. 13
·期 5
·864-873
·
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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高影响因子
EUROPEAN JOURNAL OF NEUROSCIENCE
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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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高影响因子
METABOLIC BRAIN DISEASE
·
2017
·Vol. 32
·期 3
·789-798
·
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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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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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
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再生医学
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组织工程
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纳米技术
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干细胞生物学
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高影响因子
Progress in Orthodontics
·
2024
·Vol. 25
·期 1
·1-13
·
IF 3.5
Chen Wenyuanfeng,Qu Yuan,Liu Yining,Zhang Guorui,Sharhan Hasan M.,Zhang Xinzhu,Zhang Kunwu,Cao Baocheng
Background Orthodontic pain affects the physical and mental health of patients. The spinal trigeminal subnucleus caudalis (SPVC) contributes to the transmission of pain information and serves as a relay station for integrating orofacial damage information. Recently, glial cells have been found to be crucial for both acute and maintenance phases of pain. It has also been demonstrated that rho kinase (ROCK) inhibitors can manage different pain models by inhibiting glial cell activation. Here, we hypothesized that orthodontic pain is related to glial cells in the SPVC, and Fasudil, a representative rho/rock kinase inhibitor, can relieve orthodontic pain by regulating the function of glial cells and the related inflammatory factors. In this study, we constructed a rat model of tooth movement pain and used immunofluorescence staining to evaluate the activation of microglia and astrocytes. Quantitative real-time PCR was used to detect the release of related cytokines and the expression of pain-related genes in the SPVC. Simultaneously, we investigated the effect of Fasudil on the aforementioned indicators. Results In the SPVC, the expression of c-Fos peaked on day 1 along with the expression of OX42 (related to microglial activation), CD16 (a pro-inflammatory factor), and CD206 (an anti-inflammatory factor) on day 3 after tooth movement, followed by a gradual decrease. GFAP-staining showed that the number of activated astrocytes was the highest on day 5 and that cell morphology became complex. After Fasudil treatment, the expression of these proteins showed a downward trend. The mRNA levels of pro-inflammatory factors (IL-1β and TNF-α) peaked on day 3, and the mRNA expression of the anti-inflammatory factor TGF-β was the lowest 3 days after tooth movement. Fasudil inhibited the mRNA expression of pain-related genes encoding CSF-1, t-PA, CTSS, and BDNF. Conclusion This study shows that tooth movement can cause the activation of glial cells in SPVC, and ROCK inhibitor Fasudil can inhibit the activation of glial cells and reduce the expression of the related inflammatory factors. This study presents for the first time the potential application of Fasudil in othodontic pain.
研究领域:
牙科学
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神经科学
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疼痛管理
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药理学
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高影响因子
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
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2019
·
IF 4.315
JiaJia Wang,YanJun Li,Ke Lai,QiMei Zhong,Konstantin A. Demin,Allan V. Kalueff,Cai Song
Neuroinflammation and metabolic deficits contribute to the etiology of human affective disorders, such as anxiety and depression. The zebrafish ( Danio rerio ) has recently emerged as a powerful new model organism in CNS disease modeling. Here, we exposed zebrafish to 2% glucose and 10% cholesterol for 19 days to experimentally induce type 2 diabetes (DM) and to assess stress responses, microglia , inflammation and apoptosis . We analyzed zebrafish anxiety-like behavior in the novel tank and light-dark box (Days 15–16) tests, as well as examined their biochemical and genomic biomarkers (Day 19). Confirming DM-like state in zebrafish, we found higher whole-body glucose, triglyceride , total cholesterol, low-density lipoprotein levels and glucagon mRNA expression, and lower high-density lipoprotein levels. DM zebrafish also showed anxiety-like behavior, elevated whole-body cortisol and cytokines IFN-γ and IL-4, as well as higher brain mRNA expression of the glucocorticoid receptor , CD11b (a microglial biomarker), pro-inflammatory cytokines IL-6 and TNF-α (but not IL-1β or anti-inflammatory cytokines IL-4 and IL-10), GFAP (an astrocytal biomarker), neurotrophin BDNF , its receptors p75 and TrkB, as well as apoptotic Bax and Caspase-3 (but not BCl-2 ) genes. Collectively, this supports the overlapping nature of DM-related affective pathogenesis and emphasizes the role of peripheral and central inflammation and apoptosis in DM-related affective and neuroendocrine deficits in zebrafish.
研究领域:
神经科学
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代谢紊乱
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行为科学
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炎症研究
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分子生物学
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Chang Liu,Qi Yan,Xuying Ding,Meijun Zhao,Chen Chen,Qian Zheng,Huiying Yang,Yining Xie
Brain-derived neurotrophic factor (BDNF) is a neurotrophic protein that promotes neuronal survival, increases neurotransmitter synthesis, and has potential therapeutic effects in neurodegenerative and psychiatric diseases, but its drug development has been limited by the fact that recombinant proteins of BDNF are unstable and do not penetrate the blood-brain barrier (BBB). In this study, we fused a TAT membrane-penetrating peptide with BDNF to express a recombinant protein (TBDNF), which was then PEG-modified to P-TBDNF. Protein characterization showed that P-TBDNF significantly improved the stability of the recombinant protein and possessed the ability to penetrate the BBB, and in cellular experiments, P-TBDNF prevented MPTP-induced nerve cell oxidative stress damage, apoptosis and inflammatory response, and its mechanism of action was closely related to the activation of tyrosine kinase B (TrkB) receptor and inhibition of microglia activation. In animal experiments, P-TBDNF improved motor and cognitive deficits in MPTP mice and inhibited pathological changes in Parkinson's disease (PD). In conclusion, this paper is expected to reveal the mechanism of action of P-TBDNF in inhibiting neurotoxicity, provide a new way for treating PD, and lay the foundation for the future development of recombinant P-TBDNF.
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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神经退行性疾病
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高影响因子
BRAIN RESEARCH BULLETIN
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2024
·
IF 3.5
Yingying Sun,Dandan Zhou,Anlan Liu,Yu Zhou,Yang Zhao,Yuan Yuan,Weifeng Guo,Jianxiang Li
Liangxue Tongyu Prescription (LTP) is a classic herbal formula for treating acute intracerebral hemorrhage (AICH) in China. Previous studies have shown that LTP significantly ameliorates neurological impairments and gastrointestinal dysfunction in patients with AICH. However, the underlying molecular mechanism remains unclear. The aim of this study is to investigate whether LTP exerts its neuroprotective effect on AICH rats through the microbiota-gut-brain axis and explore its potential underlying mechanism. In the current study, AICH models were established by injecting autologous whole blood into the right caudate nucleus of rats. Behavioural and pathological evaluations demonstrated that LTP ameliorated neuronal and intestinal damage in AICH rats. Analysis via western blot, quantitative real-time PCR, immunohistochemistry (IHC) and tunel staining indicated that LTP upregulated the expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor(NGF) and reduced neuronal cell apoptosis. Additionally, 16S rDNA sequencing revealed that LTP mitigated dysbiosis of intestinal microbiota in AICH rats. LTP increased the levels of noradrenaline (NA), dopamine (DA), glutamate (GLU) and modulated brain-gut peptides such as gastrin (GAS), motilin (MTL), ghrelin in AICH rats. Furthermore, LTP enhanced vagus nerve discharge. In summary, this research provides evidence suggesting that LTP’s influence on AICH may involve modulation of the microbiota-gut-brain axis, offering a potential scientific rationale for its therapeutic efficacy in improving outcomes of AICH.
研究领域:
神经科学
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药理学
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微生物学
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分子生物学
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高影响因子
Journal of Integrative Neuroscience
·
2024
·Vol. 23
·期 8
·145
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IF 2.5
Yuan Xu,Yushi Yang,Jie Yang,Junshuan Cui,Jian Yan,Jiannan Jiang,Zhangwei Yan,Hua Yang
Background: Ischemic stroke is mainly caused by cerebral artery thrombosis. This study investigated the role of glycine receptor beta subunit (GlyR-β) in the recovery from cerebral ischemia stroke/reperfusion. Methods: The oxygen glucose deprivation and recovery (OGD/R) bEnd3 cell model and the middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model were used in this study. Results: Expression of both the GlyR-β gene and vascular endothelial growth factor (Vegf), cell proliferation, and tube formation ability was decreased in bEnd3 cells after OGD/R, and was reversed by overexpression of GlyR-β. Neurological function, asindicated by Zea Longa scores, area of cerebral ischemia, and pathological changes were increased in mice after MCAO/R, and were ameliorated by overexpression of the glycine receptor beta (Glrb) gene at 24 h and 7 d after MCAO/R. Expression of GlyR-β and Gap-43 was decreased, and the expression of CD34, Vegf, and Bdnf, and cell growth as determined by a bromodeoxyuridine (BrdU) assay, increased in the affected brain tissue of MCAO/R mice in a time-dependent manner. GlyR-β overexpression resulted in enhanced expression of CD34, Vegf, Growth association protein 43 (Gap-43), and brain-derived neurotrophic factor (Bdnf) and cell growth in affected brain tissue of MCAO/R mice in a time-dependent manner. Conclusions: GlyR-β promoted potential angiogenesis and neurological regeneration in affected brain tissue, thus promoting recovery from cerebral ischemia stroke/reperfusion.
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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病理生理学
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细胞生物学
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高影响因子
Nano Today
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2024
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IF 13.2
Ziyao Chen,Dongju Zhao,Meng Cheng,Fan Yang,Yining Liu,Jin Chang,Yan Dou
Alzheimer's disease (AD) has much higher incidence and mortality in women, largely attributed to the dramatic decline in estrogen levels during menopause. Therefore, tailoring therapeutic strategies targeting estrogen deprivation is essential to achieve female-specific AD treatment. Herein, we developed a multifunctional phytoestrogen nanomodulator (LQ-LPs) and revealed its feasibility and key pharmacological mechanisms for female-sensitive AD management. Benefiting from the greatly improved bioavailability and pharmacokinetics by liposomes , LQ-LPs amplified multiple biological properties of loaded liquiritigenin against estrogen-deprived AD progression, including enhancing synaptoprotective and anti-apoptotic effects through activation of ERβ/BDNF/ERK signaling, as well as simultaneously inhibiting Ca 2+ influx spike, oxidative damage , and cholinergic dysfunction caused by glutamate excitotoxicity . Taking advantage of the favorable brain-targeting properties conferred by intranasal delivery, LQ-LP administration exhibited remarkable anti-AD efficacy in reversing ovariectomy-induced neuropathology and rescuing cognitive deficits in estrogen-deprived AD mice. This work reveals for the first time the attractive promise of phytoestrogen-derived versatile nanotherapeutics for female-specific AD management, providing advanced insights into precision drug development for female AD.
研究领域:
药理学
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纳米技术
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神经科学
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老年医学
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女性健康研究
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高影响因子
危险品化学品经营许可证（带存储）