INTERNATIONAL JOURNAL OF NEUROSCIENCE
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2021
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IF 2.292
Hongyan Wang,Huaiqing Gao
Aim Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique showing improvement effects on Parkinson’s disease (PD). Multiple microRNAs (miRs) are dys-expressed during the progression of PD. In the current study, the potential involvement of miRs in the anti-PD effects of rTMS was explored.Methods PD symptoms were induced in mice with 6-OHDA. The expression profile of miRs influenced by rTMS in PD mice was detected by microarray technique and validated by RT-qPCR detection. The PD mice were treated with rTMS and the changes in cognitive behaviors, substantia nigra neuron number, brain histology, and Aβ1-42 level were detected. The activity of miR-409-3p/PDHB axis was also detected to preliminarily explain the interaction between miRs and rTMS.Results The detection of microarray showed that 266 miRs were dys-expressed in PD mice after the administration of rTMS, including 101 up-regulated ones and 146 down-regulated ones. With validation by RT-qPCR detection, miR-409-3p was selected for subsequent assays. Administrations of rTMS improved cognitive behaviors of mice, increased neuron number, and attenuated brain injuries induced by 6-OHDA. The cerebrospinal fluid (CSF) level of Aβ1-42 was induced, while the brain level of Aβ1-42 was suppressed by rTMS. Regarding miR-409-3p/PDHB axis, rTMS administrations suppressed miR-409-3p level and increased the expression of PDHB.Conclusion Administrations of rTMS showed considerable protective effects on brain tissues against PD-induced injuries, which was associated with the changes in miR levels. The current study demonstrated that the inhibition of miR-409-3p by rTMS contributed to the attenuation of PD by inducing PDHB.
研究领域:
神经科学
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分子生物学
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PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
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2019
·Vol. 458
·期 1
·71-78
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IF 2.884
Ba Fang,Zhou Yuxin,Zhou Jie,Chen Xueyun
Repetitive transcranial magnetic stimulation (rTMS) is a technique protecting neurons against diverse neurodegenerative disorders by delivering magnetic stimuli into the brain through the intact scalp. In the current study, the protection effect of rTMS on Parkinson’s disease (PD) and the associated mechanism driving the treatment were explored. The PD symptoms were induced using 6-OHDA in mice, and the effect of rTMS of two frequencies (1 Hz and 10 Hz) on the cognitive behaviors and neuron viability was detected. Afterwards, the level of Aβ 1–42 and activity of MKK7-ERK-Fos-APP axis under the administration of rTMS were recorded as well. The intracranial injection of 6-OHDA impaired the cognitive behaviors of the mice in the test of Morris water maze as well as reducing the viability and number of neurons in PD mice. After the treatment of rTMS of both frequencies, the cognitive function of mice was improved and the neuron viability and number were restored in mice brain tissues. The administration of rTMS also increased the cerebrospinal fluid (CSF) level of Aβ 1–42 in PD mice, which was accompanied by the suppressed levels of p-MKK7, p-ERK1/2, p–c-Fos, and APP. Moreover, the effect of rTMS on mice nerve system was all exerted in a frequency-dependent manner. In conclusion, the findings outlined in the current study affirmed the protection effect of rTMS against PD. The anti-PD function of rTMS was associated with the suppression of MKK7-ERK-Fos-APP axis, which subsequently resulted in the increased CSF Aβ 1–42 level and decreased brain Aβ 1–42 level.
研究领域:
神经科学
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药理学
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神经退行性疾病
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PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
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2024
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IF 4.2
Hongying Zhao,Jiaxin Song,Tian Wang,Xiaodan Fan
Parkinson's disease (PD) is a neurodegenerative disorder and identifying disease-causing pathways and drugs that target them has remained challenging. Herein, selenium nanoparticles decorated with polysaccharides from Sargassum fusiforme (SFPS-SeNPs) were investigated on 6-OHDA-induced neurotoxicity in PC12 cells and rats. 6-OHDA can significantly increase neurotoxicity, oxidative stress and decrease the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) both in vitro and vivo. In vitro, treatment with SFPS-SeNPs can significantly decrease 6-OHDA cytotoxicity, reactive oxygen species (ROS) production or malondialdehyde (MDA) levels, and cell apoptosis, significantly increased the activity of SOD and GPx. In vivo, 6-OHDA exposure could also decrease the expression of Nrf2 and OH-1, while treatment with SFPS-SeNPs (1 mg Se/kg) increased. SFPS-SeNPs can protect neurons from 6-OHDA-induced neurotoxicity by regulating apoptosis and Nrf2/ARE pathway. The present study demonstrated that SFPS-SeNPs is a good candidate for developing a new drug against neurodegenerative diseases such as PD.
研究领域:
神经科学
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药理学
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纳米技术
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生物医学工程
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PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
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2021
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IF 6.543
Wei Wu,Hui Han,Jingwangwei Liu,Min Tang,Xiaoyu Wu,Xiaojun Cao,Tiantian Zhao,Yujia Lu,Tingting Niu,Juanjuan Chen,Haimin Chen
As the most abundant marine carotenoid extracted from seaweeds, fucoxanthin (FUC) is considered to have excellent neuroprotective activity. However, the target of FUC for its neuroprotective properties remains largely unclear. Oxidative stress is one of the initiating factors causing neuronal cell loss and necrosis, and it is also an important inducement of Parkinson’s disease (PD). In the present study, the neuroprotective effect of FUC was assessed using a 6-hydroxydopamine- (6-OHDA-) induced neurotoxicity model. FUC suppressed 6-OHDA-induced accumulation of intracellular ROS, the disruption of mitochondrial membrane potential, and cell apoptosis through the Nrf2-ARE pathway. Keap1 as a repressor of Nrf2 can regulate the activity of Nrf2. Here, the biolayer interferometry (BLI) assay demonstrated that FUC specifically targeted Keap1 and inhibited the interaction between Keap1 and Nrf2. FUC bound to the hydrophobic region of Keap1 pocket and formed hydrogen bonding interactions with Arg415 and Tyr525. Besides, it also dose-dependently upregulated the expressions of antioxidant enzymes, such as nicotinamide heme oxygenase-1, glutamate-cysteine ligase modifier subunit, and glutamate-cysteine ligase catalytic subunit, in 6-OHDA-induced PC12 cells. In 6-OHDA-exposed zebrafish, FUC pretreatment significantly increased the total swimming distance of zebrafish larvae and improved the granular region of the brain tissue damage. These results suggested that FUC could protect the neuronal cells against 6-OHDA-induced injury via targeting Keap1.
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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毒理学
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PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
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2023
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IF 3.3
Minyan Li,Sha Wang,Chunmei Fu,Hongyu Chen,Yuxia Su,Peng Wu,Xinhao Yan,Juanjuan Gao
Parkinson's disease (PD) is the second-most common neurodegenerative disease, and the development and progression of PD is characterized by oxidative stress (OS). This study determined the neuroprotective effects of salidroside (Sal). We report that Sal with scavenging ROS capabilities could regulate oxidative stress for the prevention of pathologic α-synuclein (α-syn) transmission in 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in PC12 cells. Sal exhibits effective free radical quenching ability and safe use in biological systems. The protective effects of Sal against 6-OHDA-induced neurotoxicity in PC12 cells were investigated using the DPPH method for free radical scavenging, CCK8 for cell viability, DCFH-DA for ROS levels, immunohistochemical staining for α-syn, and western blot for SOD, CAT, and GPX4 protein detection. The results obtained through our studies showed that 6-OHDA-induced neurotoxicity significantly decreased cell viability, antioxidant enzyme (SOD, CAT, and GPX4) expression, increased ROS levels, and α-syn accumulation, while on Sal (50 mg mL−1) pretreatment obviously regulated the cellular redox balance and decreased α-syn accumulation. With further study, these findings may provide new insight into the protective mechanisms against neurodegenerative diseases and synucleinopathies.
研究领域:
神经科学
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药理学
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细胞生物学
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DOI
高影响因子
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
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2022
·Vol. 322
·期 6
·G553
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IF 4.871
Yan-Yan Fan,Yue Zhang,Rui-Fang Fan,Tao Wang,Xiao Yu,Li-Fei Zheng,Jin-Xia Zhu
Download figureDownload PowerPoint Patients with Parkinson’s disease (PD) often suffer from delayed gastric emptying, but the underlying mechanism remains unclear. We have shown previously that a PD rat model comprising bilateral substantia nigra destruction by 6-hydroxydopamine (6-OHDA rats) exhibits gastroparesis with alteration of neural nitric oxide synthase (nNOS) and acetylcholine in gastric corpus. However, changes in pyloric motility in the 6-OHDA rats have not been characterized. Solid gastric emptying test, immunofluorescence, Western blot, and in vitro pyloric motility recordings were used to assess pyloric motor function in the 6-OHDA rats. The 6-OHDA-treated rats displayed delayed solid gastric emptying and a lower basal pyloric motility index. In the 6-OHDA rats, high K+-induced transient contractions were weaker in pyloric sphincters. Electric field stimulation (EFS)-induced pyloric sphincter relaxation was lower in the 6-OHDA rats. NG-nitro-l-arginine methyl ester (l-NAME), a nonselective inhibitor of NOS, markedly inhibited the EFS-induced relaxation in both control and 6-OHDA rats. Pretreatment of tetrodotoxin abolished the effect of EFS on the pyloric motility. In addition, nNOS-positive neurons were extensively distributed in the pyloric myenteric plexus, whereas the number of nNOS-immunoreactive neurons and the protein expression of nNOS were significantly decreased in the pyloric muscularis of 6-OHDA rats. However, sodium nitroprusside-induced pyloric relaxations were similar between the control and 6-OHDA rats. These results indicate that the pyloric sphincters of 6-OHDA rats exhibit both weakened contraction and relaxation. The latter may be due to reduced nNOS in the pyloric myenteric plexus. The dysfunction of the pyloric sphincter might be involved in the delayed gastric emptying.NEW & NOTEWORTHY Reduced nitrergic neurons in pyloric myenteric plexus potently contributed to the attenuated relaxation in 6-hydroxydopamine (6-OHDA) rats, subsequently affecting gastric emptying. SNP could well improve the relaxation of pylori in 6-OHDA rats. The present study provides new insight into the diagnosis and treatment of delayed gastric emptying in patients with PD.
研究领域:
神经科学
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胃肠生理学
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DOI
PubMed
高影响因子
NEUROSCIENCE LETTERS
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2023
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IF 2.5
Wanran Huang,Yanni Wang,Wei Huang
Parkinson's disease (PD) is a neurodegenerative disorder with a lack of effective treatment options. mangiferin, a bioactive compound derived from mango, has been shown to possess strong neuroprotective properties. In this study, we investigated the neuroprotective effects of mangiferin on PD and its underlying mechanisms using both in vitro and in vivo models of 6-OHDA-induced PD. Additionally, we conducted molecular docking experiments to evaluate the interaction between mangiferin and AKR1C3 and β-catenin. Our results demonstrated that treatment with mangiferin significantly attenuated 6-OHDA-induced cell damage in PC12 cells, reducing intracellular oxidative stress, improving mitochondrial membrane potential, and restoring the expression of tyrosine hydroxylase (TH), a characteristic protein of dopaminergic neurons. Furthermore, mangiferin reduced the accumulation of α-synuclein and inhibited the expression of AKR1C3, thereby activating the Wnt/β-catenin signaling pathway. In vivo studies revealed that mangiferin improved motor dysfunction in 6-OHDA-induced PD mice. Molecular docking analysis confirmed the interaction between mangiferin and AKR1C3 and β-catenin. These findings indicate that mangiferin exerts significant neuroprotective effects in 6-OHDA-induced PD by inhibiting AKR1C3 and activating the Wnt/β-catenin signaling pathway. Therefore, mangiferin may emerge as an innovative therapeutic strategy in the comprehensive treatment regimen of PD patients, providing them with better clinical outcomes and quality of life.
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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PubMed
高影响因子
Chinese Herbal Medicines
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2020
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IF 0
Xin Li,Xiao-wen Jiang,Hai-xiao Chu,Qing-chun Zhao,Huai-wei Ding,Chao-hong Cai
Objective Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in substantia nigra (SN). Our previous study demonstrated kukoamine A (KuA) to exhibit strong neuroprotective effects through antioxidative stress, and autophagy in MPTP/MPP + -induced PD models in vivo and in vitro . It is necessary to evaluate the efficacy of the anti-PD effects under various models. Methods In the present study, total chemical synthesis was used to obtain KuA, which performed low content in Lycii Cortex . Then, 6-OHDA-induced PD model of PC12 cells was used to investigate the effects of KuA on PD. Results Our results demonstrated that KuA ameliorated cell loss and mitochondrial membrane potential (MMP) loss, and inhibited Bax/Bcl-2 ratio increase that were induced by 6-OHDA. Iron accumulation in SN is thought to participate in neuronal death in PD, which subsequently resulted in oxidative stress and overexpression of α-synuclein caused by iron metabolism protein disorder. In our study, KuA could chelate cellular iron content and decrease iron influx. Moreover, KuA could upregulate the expression of ferroportin1 and Hephaestin, downregulate the expression of DMT1, TfR, and Ferritin to maintain cellular iron homeostasis avoiding neuronal death from cellular iron deposition. Moreover, KuA could decrease the expression of a-synuclein in cells. All the results indicated that KuA protected against neurotoxin-induced PD due to the apoptosis inhibition and iron homeostasis maintaining. Conclusion KuA treatment might represent a neuroprotective treatment for PD.
研究领域:
神经科学
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药理学
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细胞生物学
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神经退行性疾病
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PubMed
Journal of Integrative Neuroscience
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2026
·Vol. 25
·期 7
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IF 3.3
Wenyu Yan,Xianyue Meng,Yan Wang,Chuanfei Wei,Fabin Han,Xueli Li
Background: Parkinson’s disease (PD) is a neurodegenerative disorder marked by motor dysfunction. No definitive methods exist to repair damaged neurons. Vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) are two neuroprotective agents that work synergistically. However, these large molecular proteins have difficulty crossing the blood–brain barrier (BBB). Extracellular vesicles (EVs) offer superior targeting and low immunogenicity, making them excellent carriers. In this study we examined the protective effects of VEGF and NGF in a cell model and evaluated the therapeutic potential of VEGF–NGF contained within EVs in PD rats. Methods: EVs were isolated using sequential differential centrifugation and characterized using transmission electron microscopy, nanoparticle tracking analysis, and western blotting (WB). VEGF and NGF were loaded into the EVs using a saponin-assisted method to create VEGF@EVs, NGF@EVs, and VEGF/NGF@EVs. The viability of 6-hydroxydopamine hydrochloride (6-OHDA)-induced SH-SY5Y cells was measured using the cell counting kit-8 assay before and after treatment with VEGF and NGF. Autophagy levels were assessed using WB, and the role of autophagy was further explored using the autophagy inhibitor chloroquine. Unilateral PD rat models were established via stereotactic injection of 6-OHDA into male Sprague–Dawley rats. Behavioral changes were monitored before and after treatment. Neuronal recovery, neurotransmitter levels, and autophagy levels in the rat brains were evaluated using immunohistochemistry, enzyme-linked immunosorbent assay, and WB. Results: VEGF/NGF@EVs significantly enhanced the viability of 6-OHDA-induced SH-SY5Y cells. A complete autophagic process was identified as essential for this protective effect. The intranasal administration of VEGF/NGF@EVs improved motor behavior in PD rats, with performance better than that of single growth factor treatments. The number of tyrosine hydroxylase (TH)–positive neurons, TH protein expression, and dopamine content were significantly increased. In addition, the level of autophagy in the rat substantia nigra was elevated. Conclusions: VEGF/NGF@EVs exert protective effects in both in vitro and in vivo 6-OHDA-induced PD models by promoting autophagy, demonstrating greater efficacy than either growth factor alone. By transplanting VEGF/NGF@EVs into PD rats, we showed that these vesicles can effectively cross the BBB and deliver targeted therapy to the central nervous system. This study highlights the significant potential of EV-mediated protein transplantation strategies for treating neurological disorders.
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PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
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2025
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IF 8.4
Zhang Jia-qi,Li Shu-yi,Yin Cui,Ji Ying,Zhang Xiang,Liu Dan-yang,Yang Hang,Niu Yong,Cui Gui-yun,Zhou Chun-yi,Xiao Cheng
Anxiety and depression are common non-motor symptoms severely affecting the quality of life in patients with Parkinson’s disease, but the underlying pathophysiological mechanisms remain elusive. As dopaminergic (DA) system and the subthalamic nucleus (STN) are involved in motor control and emotional processing, we herein investigated the role of DA circuitry in the STN in regulating depression in parkinsonian mice. A hemi-parkinsonian mouse model was established by injection of 6-OHDA into the right medial forebrain bundle (MFB), desipramine (20 mg/kg, i.p.) was injected 30 min before the intracranial injection. Motor function was monitored in open field test and apomorphine-induced contra-lesional rotation and rotarod tests; anxiety- and depression-like behaviors were assessed with the open field test, elevated plus maze, tail suspension test and forced swim test. We found that the hemi-parkinsonian mice displayed motor dysfunction and depression-like behaviors at different time points. Fiber photometry recording revealed that STN neurons were hypersensitive to anxiety- and depression-like stimulation; chemogenetic inhibition of STN neurons mitigated anxiety- and depression-like behaviors. While dopamine release was significantly reduced in the STN of the parkinsonian mice in response to anxiety- and depression-like stimulation, the expression of D1- and D2-like dopamine receptors was time-dependently changed. Intracranial injection of either D1- or D2-like dopamine receptor agonist into the STN mitigated anxiety- and depression-like behaviors in the parkinsonian mice. We conclude that STN DA circuitry may be promising targets to treat anxiety and depression in PD.
研究领域:
神经科学
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药理学
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行为学
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DOI
PubMed
高影响因子
Food & Function
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2022
·Vol. 13
·期 11
·6008-6021
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IF 6.317
Rui Ma,Qiqi Chen,Yanping Dai,Yan Huang,Qing Hou,Yuting Huang,Kai Zhong,Yina Huang,Hong Gao,Qian Bu
Ocean life contains a wealth of bioactive peptides that could be utilized in nutraceuticals and pharmaceuticals. This study aimed to obtain neuroprotective antioxidant peptides in sea squirt (Halocynthia roretzi) through protamex enzymolysis. Fraction F4 (ultrafiltration generated four fractions) had a lower molecular weight (<500 Dalton (Da)) with greater 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) radical scavenging activities (94.24 ± 2.50% and 91.80 ± 1.19%). After gel filtration, six peptides, including Phe-Gly-Phe (FGF), Leu-Gly-Phe (LGF), Leu-Phe-VAL (LFV), Val-Phe-Leu (VFL), Trp-Leu-Pro (WLP), and Ile-Ser-Trp (ISW), were identified and sequenced by liquid chromatography-mass spectrometry (LC-MS/MS). Peptides WLP and ISW showed higher oxygen radical absorbance capacity (ORAC) values (2.72 ± 0.47 and 1.93 ± 0.01 μmol L−1 of Trolox equivalent (TE) per μmol L−1 of peptide) than glutathione (GSH). Additionally, WLP effectively increased cell viability, dramatically attenuated 6-Hydroxydopamine (6-OHDA)-induced cell apoptosis and decreased reactive oxygen species (ROS) levels to nearly two-fold, and significantly boosted glutathione peroxidase (GSH-Px) activity in PC12 cells. Transcriptome sequencing revealed differential expression of genes associated with various oxidative stress pathways after WLP treatment, such as glutathione metabolism. These results suggest that the Halocynthia roretzi-derived tripeptide WLP could alleviate neurodegenerative diseases associated with oxidative stress.
研究领域:
海洋生物学
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药理学
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神经科学
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生物化学
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产品关联
DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
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2023
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IF 5.5
Xiaolu Hu,Lan Yu,Yatong Li,Xiaoxi Li,Yimeng Zhao,Lijuan Xiong,Jiaxuan Ai,Qijun Chen,Xing Wang,Xiaoqing Chen,Yinying Ba,Yaonan Wang,Xia Wu
Aim Tyrosine decarboxylase (TDC) presented in the gut-associated strain Enterococcus faecalis can convert levodopa (L-dopa) into dopamine (DA), and its increased abundance would potentially minimize the availability and efficacy of L-dopa. However, the known human decarboxylase inhibitors are ineffective in this bacteria-mediated conversion. This study aims to investigate the inhibition of piperine (PIP) on L-dopa bacterial metabolism and evaluates the synergistic effect of PIP combined with L-dopa on Parkinson's disease (PD). Methods Metagenomics sequencing was adopted to determine the regulation of PIP on rat intestinal microbiota structure, especially on the relative abundance of E. faecalis . Then, the inhibitory effects of PIP on L-dopa conversion and TDC expression of E. faecalis were tested in vitro. We examined the synergetic effect of the combination of L-dopa and PIP on 6-hydroxydopamine (6-OHDA)-lesioned rats and tested the regulations of L-dopa bioavailability and brain DA level by pharmacokinetics study and MALDI-MS imaging. Finally, we evaluated the microbiota-dependent improvement effect of PIP on L-dopa availability using pseudo-germ-free and E. faecalis -transplanted rats. Results We found that PIP combined with L-dopa could better ameliorate the move disorders of 6-OHDA-lesioned rats by remarkably improving L-dopa availability and brain DA level than L-dopa alone, which was associated with the effect of PIP on suppressing the bacterial decarboxylation of L-dopa via effectively downregulating the abnormal high abundances of E. faecalis and TDC in 6-OHDA-lesioned rats. Conclusion Oral administration of L-dopa combined with PIP can improve L-dopa availability and brain DA level in 6-OHDA-lesioned rats by suppressing intestinal bacterial TDC.
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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神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）