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Electroacupuncture Downregulating Neuronal Ferroptosis in MCAO/R Rats by Activating Nrf2/SLC7A11/GPX4 Axis 电针通过激活Nrf2/SLC7A11/GPX4轴下调MCAO/R大鼠神经元铁凋亡
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-05-31 DOI: 10.1007/s11064-024-04185-x
Wei Zhu, Jianjian Dong, Yongsheng Han

Ischemic stroke involves various pathological processes, among which ferroptosis is crucial. Previous studies by our group have indicated that electroacupuncture (EA) mitigates ferroptosis after ischemic stroke; however, the precise mechanism underlying this effect remains unclear. In the present study, we developed a rat model of middle cerebral artery occlusion/reperfusion. We chose the main acupoint of the treatment methods of the “Awakening and Opening of the Brain”. Rats’ neurological function and motor coordination were evaluated by neurological function score and the rotarod test, respectively, and the volume of cerebral infarction was analyzed by 2,3,5-triphenyltetrazolium chloride Staining. The cerebrovascular conditions were visualized by time-of-flight magentic resonance angiography. In addition, we detected changes in lipid peroxidation and endogenous antioxidant activity by measuring the malondialdehyde, glutathione, superoxide dismutase activities, glutathione/oxidized glutathione and reduced nicotinamide adenine dinucleotide phosphate/oxidized nicotinamide adenine dinucleotide phosphate ratios. Inductively coupled plasma-mass spectrometry, western blot, reverse transcription-polymerase chain reaction, fluoro-jade B staining, immunofluorescence analysis, and transmission electron microscopy were utilized to examine the influence of EA. The results indicate that EA treatment was effective in reversing neurological impairment, neuronal damage, and protecting mitochondrial morphology and decreasing the cerebral infarct volume in the middle cerebral artery occlusion/reperfusion rat model. EA reduced iron levels, inhibited lipid peroxidation, increased endogenous antioxidant activity, modulated the expression of several ferroptosis-related proteins, and promoted nuclear factor-E2-related factor 2 (Nrf2) nuclear translocation. However, the protective effect of EA was hindered by the Nrf2 inhibitor ML385. These findings suggest that EA can suppress ferroptosis and decrease damage caused by cerebral ischemia/reperfusion by activating Nrf2 and increasing the protein expression of solute carrier family 7 member 11 and glutathione peroxidase 4.

缺血性脑卒中涉及多种病理过程,其中铁细胞减少是关键因素。我们小组之前的研究表明,电针(EA)可减轻缺血性中风后的铁蛋白沉着,但这种作用的确切机制仍不清楚。在本研究中,我们建立了一个大脑中动脉闭塞/再灌注大鼠模型。我们选择了 "醒脑开窍 "治疗方法的主要穴位。大鼠的神经功能和运动协调性分别通过神经功能评分和转体试验进行评价,脑梗死体积通过 2,3,5-三苯基氯化四氮唑染色法进行分析。通过飞行时间磁共振血管造影观察脑血管状况。此外,我们还通过测量丙二醛、谷胱甘肽、超氧化物歧化酶活性、谷胱甘肽/氧化谷胱甘肽和还原烟酰胺腺嘌呤二核苷酸磷酸酯/氧化烟酰胺腺嘌呤二核苷酸磷酸酯比率,检测脂质过氧化和内源性抗氧化活性的变化。利用电感耦合等离子体质谱法、Western 印迹法、逆转录聚合酶链反应、荧光玉 B 染色法、免疫荧光分析法和透射电子显微镜等方法研究了 EA 的影响。结果表明,在大脑中动脉闭塞/再灌注大鼠模型中,EA能有效逆转神经功能损伤、神经元损伤,保护线粒体形态,减少脑梗死体积。EA 可降低铁含量,抑制脂质过氧化,提高内源性抗氧化活性,调节多种铁变态反应相关蛋白的表达,促进核因子-E2 相关因子 2(Nrf2)的核转位。然而,EA 的保护作用受到 Nrf2 抑制剂 ML385 的阻碍。这些研究结果表明,EA能通过激活Nrf2和增加溶质运载家族7成员11和谷胱甘肽过氧化物酶4的蛋白表达来抑制铁变态反应,减轻脑缺血/再灌注造成的损伤。
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引用次数: 0
Schwann Cell-Derived Exosomes Induced Axon Growth after Spinal Cord Injury by Decreasing PTP-σ Activation on CSPGs via the Rho/ROCK Pathway 许旺细胞衍生的外泌体通过Rho/ROCK通路减少CSPG上PTP-σ的活化,从而诱导脊髓损伤后的轴突生长
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-05-31 DOI: 10.1007/s11064-024-04166-0
Shibo Zhu, Hongpeng Ma, Mengfan Hou, Hailiang Li, Guangzhi Ning

Spinal cord injury (SCI) is a severe neurological condition that involves a lengthy pathological process. This process leads to the upregulation of chondroitin sulfate proteoglycans (CSPGs) by reactive glia, which impedes repair and regeneration in the spinal cord. The role of the CSPG-specific receptor protein tyrosine phosphatase-sigma (PTP-σ) in post-SCI remains largely unexplored. Exosomes have great potential in the diagnosis, prognosis, and treatment of SCI due to their ability to easily cross the blood‒brain barrier. Schwann cell-derived exosomes (SCDEs) promote functional recovery in mice post-SCI by decreasing CSPG deposition. However, the mechanism by which SCDEs decrease CSPGs after SCI remains unknown. Herein, we observed elevated levels of PTP-σ and increased CSPG deposition during glial scar formation after SCI in vivo. After SCDEs were injected into SCI mice, CSPG deposition decreased in scar tissue at the injury site, the expression of PTP-σ increased during axonal growth around the injury site, and motor function subsequently recovered. Additionally, we demonstrated that the use of both Rho/ROCK inhibitors and SCDEs inhibited the reparative effects of SCDEs on scar tissue after SCI. In conclusion, our study revealed that treatment with SCDEs targeting the Rho/ROCK signaling pathway reduced PTP-σ activation in the CSPG post-SCI, which inhibited scar tissue formation.

脊髓损伤(SCI)是一种严重的神经系统疾病,涉及一个漫长的病理过程。这一过程会导致反应性神经胶质上调硫酸软骨素蛋白多糖(CSPGs),从而阻碍脊髓的修复和再生。CSPG特异性受体蛋白酪氨酸磷酸酶-σ(PTP-σ)在脊髓损伤后的作用在很大程度上仍未得到探索。由于外泌体能够轻松穿过血脑屏障,因此在 SCI 的诊断、预后和治疗方面具有巨大潜力。许旺细胞衍生的外泌体(SCDEs)通过减少CSPG沉积促进了SCI后小鼠的功能恢复。然而,SCDEs 减少 SCI 后 CSPGs 的机制仍不清楚。在此,我们观察到体内 SCI 后神经胶质疤痕形成过程中 PTP-σ 水平升高,CSPG 沉积增加。向 SCI 小鼠注射 SCDE 后,损伤部位瘢痕组织中的 CSPG 沉积减少,损伤部位周围轴突生长过程中 PTP-σ 的表达增加,运动功能随之恢复。此外,我们还证明,同时使用 Rho/ROCK 抑制剂和 SCDEs 可抑制 SCI 后 SCDEs 对瘢痕组织的修复作用。总之,我们的研究揭示了针对 Rho/ROCK 信号通路的 SCDEs 可减少 SCI 后 CSPG 中 PTP-σ 的激活,从而抑制瘢痕组织的形成。
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引用次数: 0
AdipoRon Ameliorates Synaptic Dysfunction and Inhibits tau Hyperphosphorylation through the AdipoR/AMPK/mTOR Pathway in T2DM Mice AdipoRon 可通过 AdipoR/AMPK/mTOR 途径改善 T2DM 小鼠的突触功能障碍并抑制 tau 过度磷酸化。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-05-31 DOI: 10.1007/s11064-024-04162-4
Wenyan Zhao, Wei Zhang, Yingying Hu, Yuliang Zhou, Jinying Zhao, Yahong Li, Zhipeng Xu

There is growing evidence showing that adiponectin (APN) can improve Alzheimer’s disease(AD)-like pathological changes by improving insulin resistance. However, the role of AdipoRon (an Adiponectin receptor agonist) on synaptic plasticity and cognitive dysfunction in the early stages of type 2 diabetes mellitus(T2DM) remains unknown. In this study, we investigated the neuroprotective effect and the molecular mechanism underlying the effect of AdipoRon in T2DM mice. We found that AdipoRon significantly restored the cognitive deficits in T2DM mice, including shorter escape latency, more crossing times, increased distances, and percentage of time in the target quadrant. In addition, AdipoRon treatment up-regulated synaptic proteins (PSD95, SYN, GAP43, and SYP), increased the number of hippocampal synapses and attenuated synaptic damage, including the length, the number and the density of dendritic spines in CA1 and DG regions. Furthermore, AdipoRon attenuated Tau phosphorylation at multiple AD-related sites (p-tau 205, p-tau 396, p-tau 404) by promoting AdipoR expression and activating the AMPK/mTOR pathway. Our data suggests that AdipoRon exerts neuroprotective effects on the T2DM mice, which may be mediated by the activation of the AdipoR/AMPK/mTOR signaling pathway.

越来越多的证据表明,脂肪连接素(APN)可以通过改善胰岛素抵抗来改善阿尔茨海默病(AD)样病理变化。然而,在2型糖尿病(T2DM)的早期阶段,AdipoRon(一种脂肪连接素受体激动剂)对突触可塑性和认知功能障碍的作用仍然未知。本研究探讨了 AdipoRon 对 T2DM 小鼠神经的保护作用及其分子机制。我们发现,AdipoRon能显著恢复T2DM小鼠的认知缺陷,包括更短的逃逸潜伏期、更多的穿越时间、更长的距离以及在目标象限的时间百分比。此外,AdipoRon还能上调突触蛋白(PSD95、SYN、GAP43和SYP),增加海马突触数量,减轻突触损伤,包括CA1和DG区树突棘的长度、数量和密度。此外,AdipoRon 还通过促进 AdipoR 的表达和激活 AMPK/mTOR 通路,减轻了多个 AD 相关位点(p-tau 205、p-tau 396、p-tau 404)的 Tau 磷酸化。我们的数据表明,AdipoRon对T2DM小鼠具有神经保护作用,这可能是通过激活AdipoR/AMPK/mTOR信号通路介导的。
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引用次数: 0
Activation of Ventral Tegmental Area Dopaminergic Neurons Projecting to the Parabrachial Nucleus Promotes Emergence from Propofol Anesthesia in Male Rats 激活投射到副腋核的腹侧被盖区多巴胺能神经元可促进雄性大鼠从丙泊酚麻醉中苏醒。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-05-30 DOI: 10.1007/s11064-024-04169-x
Lei Jia, Jieting Yin, Tielong Liu, Wenqiang Qi, Tongyu Du, Quntao Li, Ketao Ma, Junqiang Si, Jiangwen Yin, Yan Li

Since the clinical introduction of general anesthesia, its underlying mechanisms have not been fully elucidated. The ventral tegmental area (VTA) and parabrachial nucleus (PBN) play pivotal roles in the mechanisms underlying general anesthesia. However, whether dopaminergic (DA) projections from the VTA to the PBN play a role in mediating the effects of general anesthesia is unclear. We microinjected 6-hydroxydopamine into the PBN to damage tyrosine hydroxylase positive (TH+) neurons and found a prolonged recovery time from propofol anesthesia. We used calcium fiber photometry recording to explore the activity of TH + neurons in the PBN. Then, we used chemogenetic and optogenetic approaches either activate the VTADA-PBN pathway, shortening the propofol anesthesia emergence time, or inhibit this pathway, prolonging the emergence time. These data indicate the crucial involvement of TH + neurons in the PBN in regulating emergence from propofol anesthesia, while the activation of the VTADA-PBN pathway facilitates the emergence of propofol anesthesia.

自全身麻醉应用于临床以来,其基本机制尚未完全阐明。腹侧被盖区(VTA)和膀胱旁核(PBN)在全身麻醉的机制中起着关键作用。然而,从 VTA 到 PBN 的多巴胺能(DA)投射是否在介导全身麻醉效应中发挥作用尚不清楚。我们将 6-羟基多巴胺显微注射到 PBN,以损伤酪氨酸羟化酶阳性(TH+)神经元,结果发现异丙酚麻醉后的恢复时间延长了。我们使用钙纤维光度记录来探究脑桥中 TH+ 神经元的活动。然后,我们使用化学遗传学和光遗传学方法激活 VTADA-PBN 通路,缩短异丙酚麻醉苏醒时间,或抑制该通路,延长苏醒时间。这些数据表明,PBN 中的 TH + 神经元在调节异丙酚麻醉苏醒中起着至关重要的作用,而 VTADA-PBN 通路的激活则有利于异丙酚麻醉的苏醒。
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引用次数: 0
Mechanism of Purinergic Regulation of Neurotransmission in Mouse Neuromuscular Junction: The Role of Redox Signaling and Lipid Rafts 嘌呤能调节小鼠神经肌肉接头神经递质的机制:氧化还原信号和脂质筏的作用
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-05-30 DOI: 10.1007/s11064-024-04153-5
Arthur R. Giniatullin, Kamilla A. Mukhutdinova, Alexey M. Petrov

Acetylcholine is the main neurotransmitter at the vertebrate neuromuscular junctions (NMJs). ACh exocytosis is precisely modulated by co-transmitter ATP and its metabolites. It is assumed that ATP/ADP effects on ACh release rely on activation of presynaptic Gi protein-coupled P2Y13 receptors. However, downstream signaling mechanism of ATP/ADP-mediated modulation of neuromuscular transmission remains elusive. Using microelectrode recording and fluorescent indicators, the mechanism underlying purinergic regulation was studied in the mouse diaphragm NMJs. Pharmacological stimulation of purinoceptors with ADP decreased synaptic vesicle exocytosis evoked by both low and higher frequency stimulation. This inhibitory action was suppressed by antagonists of P2Y13 receptors (MRS 2211), Ca2+ mobilization (TMB8), protein kinase C (chelerythrine) and NADPH oxidase (VAS2870) as well as antioxidants. This suggests the participation of Ca2+ and reactive oxygen species (ROS) in the ADP-triggered signaling. Indeed, ADP caused an increase in cytosolic Ca2+ with subsequent elevation of ROS levels. The elevation of [Ca2+]in was blocked by MRS 2211 and TMB8, whereas upregulation of ROS was prevented by pertussis toxin (inhibitor of Gi protein) and VAS2870. Targeting the main components of lipid rafts, cholesterol and sphingomyelin, suppressed P2Y13 receptor-dependent attenuation of exocytosis and ADP-induced enhancement of ROS production. Inhibition of P2Y13 receptors decreased ROS production and increased the rate of exocytosis during intense activity. Thus, suppression of neuromuscular transmission by exogenous ADP or endogenous ATP can rely on P2Y13 receptor/Gi protein/Ca2+/protein kinase C/NADPH oxidase/ROS signaling, which is coordinated in a lipid raft-dependent manner.

Graphical Abstract

乙酰胆碱是脊椎动物神经肌肉接头(NMJ)的主要神经递质。乙酰胆碱的外渗受共递质 ATP 及其代谢物的精确调节。一般认为,ATP/ADP 对 ACh 释放的影响依赖于激活突触前的 Gi 蛋白偶联 P2Y13 受体。然而,ATP/ADP 介导的神经肌肉传导调节的下游信号机制仍未确定。研究人员使用微电极记录和荧光指示剂研究了小鼠膈肌 NMJ 的嘌呤能调节机制。用 ADP 对嘌呤受体进行药理刺激可减少低频和高频刺激所诱发的突触小泡外泌。这种抑制作用被 P2Y13 受体(MRS 2211)、Ca2+动员(TMB8)、蛋白激酶 C(chelerythrine)和 NADPH 氧化酶(VAS2870)的拮抗剂以及抗氧化剂所抑制。这表明 Ca2+ 和活性氧(ROS)参与了 ADP 触发的信号传导。事实上,ADP 会引起细胞膜 Ca2+ 的增加,进而导致 ROS 水平的升高。MRS 2211 和 TMB8 阻止了[Ca2+]in 的升高,而百日咳毒素(Gi 蛋白抑制剂)和 VAS2870 则阻止了 ROS 的上调。以脂质筏的主要成分胆固醇和鞘磷脂为靶点,可抑制 P2Y13 受体依赖性的外吞减弱和 ADP 诱导的 ROS 生成增强。抑制 P2Y13 受体可减少 ROS 的产生,并提高剧烈活动时的外泌率。因此,外源性 ADP 或内源性 ATP 对神经肌肉传导的抑制可能依赖于 P2Y13 受体/Gi 蛋白/Ca2+/蛋白激酶 C/NADPH 氧化酶/ROS 信号传导,这种信号传导以脂质筏依赖的方式协调进行。
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引用次数: 0
miR-206-3p Targets Brain-Derived Neurotrophic Factor and Affects Postoperative Cognitive Function in Aged Mice miR-206-3p 靶向脑源性神经营养因子并影响老年小鼠的术后认知功能
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-05-30 DOI: 10.1007/s11064-024-04174-0
Shentong Wang, Jia Zhao, Chengran Wang, Yuhan Yao, Zhiyao Song, Longyun Li, Jinlan Jiang

Postoperative cognitive dysfunction (POCD) occurs after surgery and severely impairs patients’ quality of life. Finding POCD-associated variables can aid in its diagnosis and prognostication. POCD is associated with noncoding RNAs, such as microRNAs (miRNAs), involved in metabolic function, immune response alteration, and cognitive ability impairment; however, the underlying mechanisms remain unclear. The aim of this study was to investigate hub miRNAs (i.e., miRNAs that have an important regulatory role in diseases) regulating postoperative cognitive function and the associated mechanisms. Hub miRNAs were identified by bioinformatics, and their expression in mouse hippocampus tissues was determined using real-time quantitative polymerase chain reaction. Hub miRNAs were overexpressed or knocked down in cell and animal models to test their effects on neuroinflammation and postoperative cognitive function. Six differentially expressed hub miRNAs were identified. miR-206-3p was the only broadly conserved miRNA, and it was used in follow-up studies and animal experiments. Its inhibitors reduced the release of proinflammatory cytokines in BV-2 microglia by regulating its target gene, brain-derived neurotrophic factor (BDNF), and the downstream signaling pathways. miR-206-3p inhibition suppressed microglial activation in the hippocampi of mice and improved learning and cognitive decline. Therefore, miR-206-3p significantly affects POCD, implying its potential as a therapeutic target.

手术后会出现认知功能障碍(POCD),严重影响患者的生活质量。找到与 POCD 相关的变量有助于诊断和预后。POCD 与参与代谢功能、免疫反应改变和认知能力损伤的非编码 RNAs(如 microRNAs,miRNAs)有关,但其潜在机制仍不清楚。本研究旨在研究调控术后认知功能的枢纽 miRNA(即在疾病中具有重要调控作用的 miRNA)及其相关机制。研究人员通过生物信息学方法鉴定了枢纽miRNA,并利用实时定量聚合酶链反应测定了它们在小鼠海马组织中的表达。在细胞和动物模型中过表达或敲除枢纽miRNA,以检测它们对神经炎症和术后认知功能的影响。研究发现了六种不同表达的中枢 miRNA,其中 miR-206-3p 是唯一一种广泛保守的 miRNA,它被用于后续研究和动物实验。其抑制剂通过调节其靶基因脑源性神经营养因子(BDNF)和下游信号通路,减少了 BV-2 小胶质细胞中促炎细胞因子的释放。抑制 miR-206-3p 可抑制小鼠海马中的小胶质细胞活化,改善学习和认知能力下降。因此,miR-206-3p 对 POCD 有重大影响,意味着它有可能成为治疗靶点。
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引用次数: 0
Effect of Capsaicin on 3-NP-Induced Neurotoxicity: A Pre-Clinical Study 辣椒素对 3-NP 诱导的神经毒性的影响:临床前研究
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-05-30 DOI: 10.1007/s11064-024-04158-0
Sakshi Tyagi, Ajit Kumar Thakur

The study objectives are to investigate the ability of capsaicin to revert the toxic effects in glutamate and lipopolysaccharide (LPS)-induced neurotoxicity in Neuro2a (N2a) cells as well as thwarting cognitive impairments, mitochondrial deficits, and oxidative insults induced by 3-nitropropanoic acid (3-NP) in a rodent model of Huntington’s disease. In-vitro study with N2a cells was performed through MTT and LDH assay and their biochemical examinations were also performed. 3-NP-administered mice (n = 6) were treated with capsaicin (5, 10, and 20 mg/kg) through the per-oral (p.o.) route for 7 consecutive days. Physiological and behavioral studies were performed in drug-treated mice. After behavioral studies, biochemical parameters were performed for cytokines levels, various oxidative stress parameters, and mitochondrial enzyme complex activities with mitochondrial permeability. N2a cells treated with capsaicin demonstrated neuroprotective effects and reduced neurotoxicity. Based on experimental observation, in an in-vitro study, the effective dose of CAP was 50 µM. Moreover, a 100 µM dose of capsaicin had toxic effects on neuronal cells (N2a cells). On the other hand, the effective dose of 3-NP was 20 mg/kg, (p.o.) in animals (in-vivo). All tested doses of capsaicin upturned the cognitive impairment and motor in-coordination effects induced by 3-NP. 3-NP-injected mice demonstrated substantially increased pro-inflammatory cytokine concentrations, defective mitochondrial complex activity, and augmented oxidative insult. However, capsaicin at different doses reduced oxidative damage and cytokines levels and improved mitochondrial complex activity along with mitochondrial permeability. Furthermore, capsaicin (10 and 20 mg/kg) improved the TNF-α concentration. These findings suggested because of the anti-inflammatory and antioxidant effect, capsaicin can be considered a novel treatment for the management of neurodegenerative disorders by reverting the antioxidant enzyme activity, pro-inflammatory cytokines concentration, and mitochondrial functions.

研究的目的是探讨辣椒素能否逆转谷氨酸和脂多糖(LPS)诱导的神经毒性对神经2a(N2a)细胞的影响,以及能否挫败3-硝基丙酸(3-NP)在亨廷顿氏病啮齿动物模型中诱导的认知障碍、线粒体缺陷和氧化损伤。通过 MTT 和 LDH 试验对 N2a 细胞进行了体外研究,并对其进行了生化检查。连续 7 天通过口服(p.o.)途径用辣椒素(5、10 和 20 毫克/千克)治疗服用 3-NP 的小鼠(n = 6)。对用药小鼠进行了生理和行为研究。行为研究后,对细胞因子水平、各种氧化应激参数、线粒体酶复合物活性和线粒体通透性等生化参数进行了检测。经辣椒素处理的 N2a 细胞具有神经保护作用,并降低了神经毒性。根据实验观察,在体外研究中,辣椒素的有效剂量为 50 µM。此外,100 µM剂量的辣椒素会对神经细胞(N2a细胞)产生毒性作用。另一方面,3-NP 对动物(体内)的有效剂量为 20 毫克/千克(口服)。所有测试剂量的辣椒素都能逆转 3-NP 引起的认知障碍和运动不协调效应。注射 3-NP 的小鼠表现出促炎细胞因子浓度大幅增加、线粒体复合物活性缺陷和氧化损伤加剧。然而,不同剂量的辣椒素可降低氧化损伤和细胞因子水平,改善线粒体复合物活性和线粒体通透性。此外,辣椒素(10 毫克/千克和 20 毫克/千克)还能改善 TNF-α 的浓度。这些研究结果表明,由于辣椒素具有抗炎和抗氧化作用,它可以通过恢复抗氧化酶活性、促炎细胞因子浓度和线粒体功能来治疗神经退行性疾病。
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引用次数: 0
Advances in Exosome-Based Therapies for the Repair of Peripheral Nerve Injuries 基于外泌体的外周神经损伤修复疗法的进展。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-05-28 DOI: 10.1007/s11064-024-04157-1
Sana Rahimian, Hossein Najafi, Christine A. Webber, Hanieh Jalali

Peripheral nerve injuries (PNIs) are the term used to describe injuries that occur to the nerve fibers of the peripheral nervous system (PNS). Such injuries may be caused by trauma, infection, or aberrant immunological response. Although the peripheral nervous system has a limited capacity for self-repair, in cases of severe damage, this process is either interrupted entirely or is only partially completed. The evaluation of variables that promote the repair of peripheral nerves has consistently been a focal point. Exosomes are a subtype of extracellular vesicles that originate from cellular sources and possess abundant proteins, lipids, and nucleic acids, play a critical role in facilitating intercellular communication. Due to their modifiable composition, they possess exceptional capabilities as carriers for therapeutic compounds, including but not limited to mRNAs or microRNAs. Exosome-based therapies have gained significant attention in the treatment of several nervous system diseases due to their advantageous properties, such as low toxicity, high stability, and limited immune system activation. The objective of this review article is to provide an overview of exosome-based treatments that have been developed in recent years for a range of PNIs, including nerve trauma, diabetic neuropathy, amyotrophic lateral sclerosis (ALS), glaucoma, and Guillain-Barre syndrome (GBS). It was concluded that exosomes could provide favorable results in the improvement of peripheral PNIs by facilitating the transfer of regenerative factors. The development of bioengineered exosome therapy for PNIs should be given more attention to enhance the efficacy of exosome treatment for PNIs.

Graphical Abstract

Inspired by the positive effects of exosomes on peripheral nerve regeneration, the figure illustrates the rejuvenating effect of exosomes on the peripheral nervous system

周围神经损伤(PNIs)是指发生在周围神经系统(PNS)神经纤维上的损伤。此类损伤可能由创伤、感染或异常免疫反应引起。尽管周围神经系统的自我修复能力有限,但在严重损伤的情况下,这一过程要么完全中断,要么只能部分完成。对促进周围神经修复的变量进行评估一直是一个焦点。外泌体是细胞外囊泡的一种亚型,来源于细胞,含有丰富的蛋白质、脂类和核酸,在促进细胞间通信方面发挥着关键作用。由于外泌体的组成可以改变,因此具有作为治疗化合物(包括但不限于 mRNA 或 microRNA)载体的特殊能力。由于外泌体具有低毒性、高稳定性和有限的免疫系统激活等优势特性,它在治疗多种神经系统疾病方面受到了广泛关注。这篇综述文章的目的是概述近年来针对神经创伤、糖尿病神经病变、肌萎缩性脊髓侧索硬化症(ALS)、青光眼和格林-巴利综合征(GBS)等一系列神经系统疾病开发的基于外泌体的疗法。研究认为,外泌体可通过促进再生因子的转移,在改善外周神经损伤方面取得良好效果。为提高外泌体治疗 PNIs 的疗效,应更加重视开发用于 PNIs 的生物工程外泌体疗法。
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引用次数: 0
Correction to: Knock‑Down of CD24 in Astrocytes Aggravates Oxyhemoglobin‑Induced Hippocampal Neuron Impairment Correction to:敲除星形胶质细胞中的 CD24 会加重氧合血红蛋白诱导的海马神经元损伤
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-05-27 DOI: 10.1007/s11064-024-04155-3
Xiang‑Xin Chen, Tao Tao, Sen Gao, Han Wang, Xiao‑Ming Zhou, Yong‑Yue Gao, Chun‑Hua Hang, Wei Li
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引用次数: 0
Physical Exercise-Induced Activation of NRF2 and BDNF as a Promising Strategy for Ferroptosis Regulation in Parkinson’s Disease 体育锻炼诱导的 NRF2 和 BDNF 激活有望成为调节帕金森病铁蛋白沉积的策略。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-05-24 DOI: 10.1007/s11064-024-04152-6
Anand Thirupathi, Luis Felipe Marqueze, Tiago F. Outeiro, Zsolt Radak, Ricardo A. Pinho

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. Ferroptosis, an iron-dependent form of regulated cell death, may contribute to the progression of PD owing to an unbalanced brain redox status. Physical exercise is a complementary therapy that can modulate ferroptosis in PD by regulating the redox system through the activation of nuclear factor (erythroid-derived 2)-like 2 (NRF2) and brain-derived neurotrophic factor (BDNF) signaling. However, the precise effects of physical exercise on ferroptosis in PD remain unclear. In this review, we explored how physical exercise influences NRF2 and BDNF signaling and affects ferroptosis in PD. We further investigated relevant publications over the past two decades by searching the PubMed, Web of Science, and Google Scholar databases using keywords related to physical exercise, PD, ferroptosis, and neurotrophic factor antioxidant signaling. This review provides insights into current research gaps and demonstrates the necessity for future research to elucidate the specific mechanisms by which exercise regulates ferroptosis in PD, including the assessment of different exercise protocols and their long-term effects. Ultimately, exploring these aspects may lead to the development of improved exercise interventions for the better management of patients with PD.

帕金森病(PD)是一种进行性神经退行性疾病,其特征是黑质中多巴胺能神经元的丧失。由于大脑氧化还原状态失衡,铁中毒(一种依赖铁的调节性细胞死亡形式)可能会导致帕金森病的进展。体育锻炼是一种辅助疗法,可通过激活核因子(红细胞衍生 2)-类 2(NRF2)和脑源性神经营养因子(BDNF)信号来调节氧化还原系统,从而调节帕金森病的铁氧化。然而,体育锻炼对帕金森病铁氧化的确切影响仍不清楚。在这篇综述中,我们探讨了体育锻炼如何影响 NRF2 和 BDNF 信号传导,以及如何影响帕金森病的铁蛋白沉积。我们使用与体育锻炼、帕金森病、铁突变和神经营养因子抗氧化信号转导相关的关键词搜索了 PubMed、Web of Science 和 Google Scholar 数据库,进一步研究了过去二十年中的相关文献。本综述深入探讨了目前的研究空白,并表明未来研究有必要阐明运动调节帕金森病铁蛋白沉积的具体机制,包括评估不同的运动方案及其长期影响。最终,对这些方面的探索可能会开发出更好的运动干预措施,从而更好地管理帕金森病患者。
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Neurochemical Research
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