Frontiers in Neuroscience
·
2023
·
IF 4.3
Xue Tao,Wang Shu,Chen Shujun,Wang Huizhi,Liu Chong,Shi Lin,Bai Yutong,Zhang Chunkui,Han Chunlei,Zhang Jianguo
Background: Focal motor seizures that originate in the motor region are a considerable challenge because of the high risk of permanent motor deficits after resection. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a potential treatment for motor epilepsy that may enhance the antiepileptic actions of the substantia nigra pars reticulata (SNr). Orexin and its receptors have a relationship with both STN-DBS and epilepsy. We aimed to investigate whether and how STN inputs to the SNr regulate seizures and the role of the orexin pathway in this process.Methods: A penicillin-induced motor epileptic model in adult male C57BL/6 J mice was established to evaluate the efficacy of STN-DBS in modulating seizure activities. Optogenetic and chemogenetic approaches were employed to regulate STN-SNr circuits. Selective orexin receptor type 1 and 2 antagonists were used to inhibit the orexin pathway.Results: First, we found that high-frequency ipsilateral or bilateral STN-DBS was effective in reducing seizure activity in the penicillin-induced motor epilepsy model. Second, inhibition of STN excitatory neurons and STN-SNr projections alleviates seizure activities, whereas their activation amplifies seizure activities. In addition, activation of the STN-SNr circuits also reversed the protective effect of STN-DBS on motor epilepsy. Finally, we observed that STN-DBS reduced the elevated expression of orexin and its receptors in the SNr during seizures and that using a combination of selective orexin receptor antagonists also reduced seizure activity.Conclusion: STN-DBS helps reduce motor seizure activity by inhibiting the STN-SNr circuit. Additionally, orexin receptor antagonists show potential in suppressing motor seizure activity and may be a promising therapeutic option in the future.
研究领域:
神经科学
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医学
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药理学
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DOI
PubMed
高影响因子
Antioxidants
·
2024
·Vol. 13
·期 10
·1183
·
IF 6
Hao Wu,Zhen-Hua Zhang,Ping Zhou,Xin Sui,Xi Liu,Yi Sun,Xin Zhao,Xiao-Ping Pu
Degeneration and death of dopaminergic neurons in the substantia nigra of the midbrain are the main pathological changes in Parkinson’s disease (PD); however, the mechanism underlying the selective vulnerability of specific neuronal populations in PD remains unclear. Here, we used single-cell RNA sequencing to identify seven cell clusters, including oligodendrocytes, neurons, astrocytes, oligodendrocyte progenitor cells, microglia, synapse-rich cells (SRCs), and endothelial cells, in the substantia nigra of a rotenone-induced rat model of PD based on marker genes and functional definitions. We found that SRCs were a previously unidentified cell subtype, and the tight interactions between SRCs and other cell populations can be improved by icaritin, which is a flavonoid extracted fromEpimedium sagittatumMaxim. and exerts anti-neuroinflammatory, antioxidant, and immune-improving effects in PD. We also demonstrated that icaritin bound with transcription factors of SRCs, and icaritin application modulated synaptic characterization of SRCs, neuroinflammation, oxidative stress, and survival of dopaminergic neurons, and improved abnormal energy metabolism, amino acid metabolism, and phospholipase D metabolism of astrocytes in the substantia nigra of rats with PD. Moreover, icaritin supplementation also promotes the recovery of the physiological homeostasis of the other cell clusters to delay the pathogenesis of PD. These data uncovered previously unknown cellular diversity in a rat model of Parkinson’s disease and provide insights into the promising therapeutic potential of icaritin in PD.
研究领域:
神经科学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MINERALS ENGINEERING
·
2025
·
IF 5
Xiaoxue Ma,Hao Zhang,Haifeng Wang,Zhuyan Ge,Guangwen Zhang,Ruoxi Zhao,Juan Hao,Shuai Wang,Weining Xie,Yaqun He
The separation of cathode and anode materials is essential for recycling spent lithium-ion batteries (LIBs). Due to graphite’s high hydrophobicity, flotation is the preferred method for separating black mass, graphite in the anode material is suitable for flotation due to its high hydrophobicity, but its fine particle size (<15 um) hinders particle-bubble collision and true flotation. However, the fine particle size of electrode materials hinders effective separation in conventional flotation. Therefore, micro-nano bubble enhanced flotation was investigated, and its mechanism was analyzed. Both micro-nano and conventional flotation methods were compared to assess their efficiency in graphite separation under varying parameters. The graphite concentrate grade peaks and then declines with slurry concentration, kerosene, and methyl isobutyl carbinol (MIBC) dosage, while recovery rises and then stabilizes. Under the optimal conditions of a flotation time of 3 min, a pulp density of 40 g/L, a kerosene dosage of 300 g/t, and an MIBC dosage of 150 g/t, the graphite grade of the micro-nano bubble flotation concentrate can reach 89.22 %, with a recovery rate of 85.83 %. Under the optimal conditions, the flotation rate constant k of micro-nano bubble flotation reaches 0.779, while conventional flotation only achieves 0.492, indicating that micro-nano bubbles significantly enhance the flotation separation performance. Contact angle measurements and optical microscopy revealed that micro-nano bubbles enhance the hydrophobicity of graphite and promote particle aggregation.
研究领域:
环境科学
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资源循环利用
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矿物加工
·
电化学储能
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界面科学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Lanxin Li,Yang Zhang,Zhengqian Chen,Can Xu,Zhongqiu Xu,Haitao Pei,Wei Wang,Ruyong Yao,Cui Hao
Parkinson's disease (PD) is a common age-related neurodegenerative disorder, which may be largely due to the mitochondrial dysfunction and impaired mitophagy. Thus, it is of great importance to seek novel therapeutic strategies for PD targeting mitochondrial function and mitophagy. Cytarabine is a marine-derived antimetabolite used in the treatment of acute leukemia, which is also used in the study of the nervous system. In this study, we found that cytarabine pretreatment significantly inhibited the apoptosis and necrosis in the ROT-induced SH-SY5Y cell PD model and reduced the oxidative stress, as evidenced by the reduced MDA levels and the increased levels of SOD, GSH, and total antioxidant capacity. Cytarabine can also enhance mitochondrial vitality, improve mitochondrial respiratory function, and preserve mitochondrial morphology. Cytarabine also enhanced the expression of the mitophagy-related proteins PINK1, Parkin, VDAC1, and DJ-1, and its actions can be reversed by treatment with AMPK inhibitor - Compound C (CC), suggesting that AMPK activation may be involved in cytarabine-enhanced mitophagy. Furthermore, cytarabine can also ameliorate the motor symptoms in the MPTP-induced PD-like mice model, and attenuate the neuropathy in the substantia nigra (SN) of PD mice, while Compound C antagonized cytarabine's beneficial effects. In summary, marine-derived compound cytarabine could resist neurological damage both in vitro and in vivo by activating AMPK to increase PINK1/Parkin-induced mitophagy, serving as a promising disease modulator for treating neurodegenerative disease.
研究领域:
神经科学
·
药理学
·
细胞生物学
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神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2016
·
IF 5.583
Nan Wang,Xin Jin,Dongbo Guo,Gangsheng Tong,Xinyuan Zhu
Iron accumulation in substantia nigra pars compacta (SNpc) has been proved to be a prominent pathophysiological feature of Parkinson’s diseases (PD), which can induce the death of dopaminergic (DA) neurons, up-regulation of reactive oxygen species (ROS), and further loss of motor control. In recent years, iron chelation therapy has been demonstrated to be an effective treatment for PD, which has shown significant improvements in clinical trials. However, the current iron chelators are suboptimal due to their short circulation time, side effects, and lack of proper protection from chelation with ions in blood circulation. In this work, we designed and constructed iron chelation therapeutic nanoparticles protected by a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) to delay the saturation of iron chelators in blood circulation and prolong the in vivo lifetime, with HIV-1 trans-activating transcriptor (TAT) served as a shuttle to enhance the blood-brain barrier (BBB) permeability. We explored and investigated whether the Parkinsonian neurodegeneration and the corresponding symptoms in behaviors and physiologies could be prevented or reversed both in vitro and in vivo. The results demonstrated that iron chelator loaded therapeutic nanoparticles could reverse functional deficits in Parkinsonian mice not only physiologically but also behaviorally. On the contrary, both untreated PD mice and non-TAT anchored nanoparticle treated PD mice showed similar loss in DA neurons and difficulties in behaviors. Therefore, with protection of zwitterionic polymer and prolonged in vivo lifetime, iron chelator loaded nanoparticles with delayed saturation provide a PD phenotype reversion therapy and significantly improve the living quality of the Parkinsonian mice.
研究领域:
神经科学
·
药学
·
纳米技术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2021
·Vol. 23
·期 1
·1-10
·
IF 2.447
Tian Zhang,Tan Wang,Xinxu Chen,Zhenqiang Zhao,Zhibin Chen
The composition of the intestinal flora of patients with Parkinson's disease (PD) can change. However, whether reshaping the gut microbial composition can treat PD remains to be seen. The present study evaluated the effect of intestinal flora in the treatment of PD in a C57BL/6 mouse PD model induced by 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP). Chronic, low‑dose, MPTP‑treated mice exhibited upregulated gene expression levels of TNF‑α and IL‑1β in the substantia nigra (SN) of the mice, and induced intestinal microbial disorders. This indicated that the chronic low‑dose MPTP model could be used to evaluate the progress of early intestinal pathology and intestinal flora imbalance in PD. After transplantation of faecal bacteria to MPTP‑induced PD mice, the level of inflammation in the SN of the mice was reduced, and motor dysfunction was alleviated. Notably, faecal microbiota transplantation (FMT) upregulated the abundance of Blautia but downregulated Anaerostipes, Bifidobacterium, ASF356 and Ruminococcus in the gut of PD mice. In addition, FMT reduced the activation of microglia and astrocytes in the SN and reduced the expression levels of GSK3β, IL‑1β, inducible nitric oxide synthase and phosphorylated PTEN in the SN. Overall, the present study demonstrated that gut microbial dysfunction is associated with the pathogenesis of PD, and that FMT can protect PD mice by inhibiting neuroinflammation.
研究领域:
神经科学
·
微生物学
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
iScience
·
2023
·
IF 5.8
Zhidan Liu,Kang Kang,Shulin Shan,Shuai Wang,Xianjie Li,Hui Yong,Zhengcheng Huang,Yiyu Yang,Zhaoxiong Liu,Yanan Sun,Yao Bai,Fuyong Song
Exposure to carbon disulfide (CS 2 ) has been associated with an increased incidence of parkinsonism in workers, but the mechanism underlying this association remains unclear. Using a rat model, we investigated the effects of chronic CS 2 exposure on parkinsonian pathology. Our results showed that CS 2 exposure leads to significant motor impairment and neuronal damage, including loss of dopaminergic neurons and degeneration of the substantia nigra pars compacta (SNpc). The immunoassays revealed that exposure to CS 2 induces aggregation of α-synuclein and phosphorylated α-synuclein, as well as activation of necroptosis in the SNpc. Furthermore, in vitro and in vivo experiments demonstrated that the interaction between α-synuclein and the necrosome complex (RIP1, RIP3, and MLKL) is responsible for the loss of neuronal cells after CS 2 exposure. Taken together, our results demonstrate that CS 2 -mediated α-synuclein aggregation can induce dopaminergic neuron damage and parkinsonian behavior through interaction with the necrosome complex.
研究领域:
神经科学
·
毒理学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2021
·Vol. 178
·期 24
·4808-4825
·
IF 8.74
Yan-Fei Yang,Hui Dong,Yan Shen,Lei Li,Michael Lazarus,Wei-Min Qu,Zhi-Li Huang
Background and Purpose Modafinil is a potent eugeroic (wakefulness-promoting) drug that is prescribed to treat narcolepsy and has a low incidence of abuse. Although previous studies have shown that modafinil-induced arousal depends on the dopamine receptors and transporters, the specific part/s of the dopamine transmitter system underlying this mechanism remained unclear. Here, we investigated the role of mesencephalic dopamine neurons in modafinil-evoked arousal. Experimental Approach A dopamine indicator (dLight1.1) was employed to detect dopamine changes in the nucleus accumbens (NAc) and dorsal striatum. We specifically lesioned mesencephalic dopamine neurons via diphtheria toxin (DTA) in the dopamine transporter (DAT)-Cre mice. Then, the sleep–wake states were recorded to evaluate the effect of modafinil on arousal. Finally, the extent of DTA-induced lesions was determined by immunohistochemistry. Key Results Modafinil promptly increased dopamine levels in the NAc and dorsal striatum in a dose-dependent manner. Lesioning of dopamine neurons in the substantia nigra pars compacta (SNc) or ventral tegmental area (VTA) had no significant effects on physiological sleep–wake cycles. Modafinil at 90 mg·kg −1 increased continuous wakefulness for 355 min in control mice. However, these effects were slightly decreased by 6.7% in the SNc-lesioned mice and were prominently diminished by 32.8% in VTA-lesioned mice. Furthermore, the modafinil-induced arousal was completely blocked in the SNc-VTA-lesioned mice, whereas lesions of the dorsal raphé nucleus had no effect. Conclusion and Implications Taken together, our findings indicate that mesencephalic dopamine neurons are essential for modafinil-induced arousal. Graphical
研究领域:
神经科学
·
药理学
·
睡眠医学
✓ 已验证
DOI
PubMed
高影响因子
Neurotherapeutics
·
2023
·
IF 5.7
Qiao Chen-Meng,Zhou Yu,Quan Wei,Ma Xiao-Yu,Zhao Li-Ping,Shi Yun,Hong Hui,Wu Jian,Niu Gu-Yu,Chen Yu-Nuo,Zhu Shan,Cui Chun,Zhao Wei-Jiang,Shen Yan-Qin
Accumulating data support a crucial role of gut microbiota in Parkinson’s disease (PD). However, gut microbiota vary with age and, thus, will affect PD in an age-dependent, but unknown manner. We examined the effects of fecal microbiota transplantation (FMT) pretreatment, using fecal microbiota from young (7 weeks) or aged mice (23 months), on MPTP-induced PD model. Motor function, pathological changes, striatal neurotransmitters, neuroinflammation, gut inflammation and gut permeability were examined. Gut microbiota composition and metabolites, namely short-chain fatty acids (SCFAs), were analyzed. Neurogenesis was also evaluated by measuring the number of doublecortin-positive (DCX + ) neurons and Ki67-positive (Ki67 + ) cells in the hippocampus. Expression of Cd133 mRNA, a cellular stemness marker, in the hippocampus was also examined. Mice who received FMT from young mice showed MPTP-induced motor dysfunction, and reduction of striatal dopamine (DA), dopaminergic neurons and striatal tyrosine hydroxylase (TH) levels. Interestingly and unexpectedly, mice that received FMT from aged mice showed recovery of motor function and rescue of dopaminergic neurons and striatal 5-hydroxytryptamine (5-HT), as well as decreased DA metabolism after MPTP challenge. Further, they showed improved metabolic profiling and a decreased amount of fecal SCFAs. High-throughput sequencing revealed that FMT remarkably reshaped the gut microbiota of recipient mice. For instance, levels of genus Akkermansia and Candidatus Saccharimonas were elevated in fecal samples of recipient mice receiving aged microbiota (AM + MPTP mice) than YM + MPTP mice. Intriguingly, both young microbiota and aged microbiota had no effect on neuroinflammation, gut inflammation or gut permeability. Notably, AM + MPTP mice showed a marked increase in DCX + neurons, as well as Ki67 + cells and Cd133 expression in the hippocampal dentate gyrus (DG) compared to YM + MPTP mice. These results suggest that FMT from aged mice augments neurogenesis, improves motor function and restores dopaminergic neurons and neurotransmitters in PD model mice, possibly through increasing neurogenesis.
研究领域:
神经科学
·
微生物学
·
药理学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2020
·
IF 6.17
Kang Han,Xiaofang Jin,Xin Guo,Guoli Cao,Siyu Tian,Yiming Song,Yuanyuan Zuo,Peng Yu,Guofen Gao,Yan-Zhong Chang
The transcription factor NF-E2-related factor 2 (Nrf2) is a central regulator of cellular antioxidant and detoxification response. The association between Nrf2 activity and iron-related oxidative stress in neurodegenerative diseases has been studied, and Nrf2 was found to transcriptionally regulate the expression of iron transporters and ferroptosis-related factors. However, the role of Nrf2 in age-related motor dysfunction and its link to iron metabolism dysregulation in brain have not been fully elucidated. In this study, with different ages of Nrf2 knockout (KO) and wild type (WT) mice, we investigated the effects of Nrf2 deficiency on brain oxidative stress, iron metabolism and the motor coordination ability of mice. In contrast to the predicted neuroprotective role of Nrf2 in oxidative stress-related diseases , we found that Nrf2 KO remarkably improved the motor coordination of aged mice, which was associated with the reduced ROS level and decreased apoptosis of dopaminergic neurons in substantia nigra (SN) of 18-month-old Nrf2 KO mice . With high-iron and Parkinson's disease (PD) mouse models, we revealed that Nrf2 KO prevented the deposition of brain iron, particularly in SN and striatum, which may subsequently delay motor dysfunction in aged mice. The regulation of Nrf2 KO on brain iron metabolism was likely mediated by decreasing the ferroportin 1 (FPN1) level on brain microvascular endothelial cells , thus hindering the process of iron entry into the brain. Nrf2 may be a potential therapeutic target in age-related motor dysfunction diseases for its role in regulating brain iron homeostasis .
研究领域:
神经科学
·
分子生物学
·
衰老研究
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2019
·
IF 3.845
Zhong Zhi-feng,Han Jing,Zhang Ji-Zhou,Xiao Qing,Chen Jing-yan,Zhang Kai,Hu Juan,Chen Li-dian
Salidroside, a phenylpropanoid glycoside, is the main bioactive component of Rhodiola rosea L. Salidroside has prominent anti-stroke effects in cerebral ischemia/reperfusion models. However, the underlying mechanisms of its actions are poorly understood. This study examined the anti-stroke effects of salidroside in middle cerebral artery occlusion (MCAO)-induced rat model of stroke and its potential mechanisms involving the dopaminergic system. Salidroside administration increased the levels of dopamine (DA), homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) in the ipsilateral striatum after induction of transient ischemia, which were assessed using microdialysis with high-performance liquid chromatography coupled with electrochemical detection (HPLC-ECD). Furthermore, treatment with salidroside ameliorated neurobehavioral impairment, assessed with the modified neurological severity scores (mNSS), the balance beam test, and the foot fault test. Moreover, enzyme-linked immunosorbent assay (ELISA) suggested that MCAO-induced reduction in monoamine oxidase (MAO) was inhibited by salidroside. Immunohistochemical and immunofluorescence analyses revealed high level of tyrosine hydroxylase (TH) in the ipsilateral striatal caudate putamen (CPu) after cerebral ischemia/reperfusion, which could be further elevated by salidroside. In addition, salidroside could reverse the decreased immunoreactivity of TH in the substantia nigra pars compacta (SNpc). These results suggest that the anti-stroke effects of salidroside in MCAO-induced cerebral ischemia/reperfusion may involve the modulation of monoamine metabolism in the striatum and SNpc, which may be related to the function of the dopaminergic system in the rat brain.
研究领域:
神经科学
·
药理学
·
神经病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 8
·期 4
·758-766
·
IF 5.047
Dong Han,Baolin Zhang,Chuangang Chong,Cuiping Rong,Jie Tan,Rusen Yang
Effective attachment of magnetic nanoparticles to neuronal membranes has far-reaching significance in activating ion channels and treating neurodegenerative diseases. Superparamagnetic iron oxide nanoparticles (SPIONs) synthesized by the polyol pyrolysis method have the advantages of rich surface functional groups, excellent magnetic properties, controllable particle size and water dispersibility. We propose that perfusion of biotin into the targeted brain area should be initially performed because it tends to be adsorbed by cell membranes, followed by injection of streptavidin (SA)-modified SPIONs into the same area of the brain. By means of the strong binding force between SA and biotin, the SPIONs may subsequently adhere to the cell surfaces in the brain area. In this work, fluorescein isothiocyanate-streptavidin (FITC-SA) was modified on the surface of polyethylene imine (PEI)-SPIONs by the EDC–NHS method and stereotaxically injected into the biotin-supplemented substantia nigra of mice. The combination of fluorescence detection with transmission electron microscopy (TEM) confirmed that FITC-SA/PEI-SPIONs adhered to neuronal membranes in the substantia nigra of mice 24 h after injection. The results show that our strategy can promote the attachment of SPIONs to neuronal membranes.
研究领域:
神经科学
·
纳米技术
·
生物医学工程
·
分子生物学
✓ 已验证
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）