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The possible protective effect of l-cysteine in a rat model of sciatic nerve ischemia-reperfusion: A possible role for NRF1 and Caspase 3; Biochemical, Histological, and Immunohistochemical study L-半胱氨酸对大鼠坐骨神经缺血再灌注模型的可能保护作用;NRF1 和 Caspase 3 的可能作用(生化、组织学和免疫组化研究)。
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-03-07 DOI: 10.1016/j.jchemneu.2024.102412
Sara Mohamed Naguib Abdel Hafez , El-Shimaa M.N. abdelhafez

Organ damage brought on by ischemia is exacerbated by the reperfusion process. L-cysteine is a semi-essential amino acid that acts as a substrate for cystathionine-β-synthase in the central nervous system. The aim of this study was to investigate the possible protective effects of L- cysteine against the structural and biochemical changes that occur in the rat sciatic nerve after ischemia reperfusion (I/R) and to address some of the underlying mechanisms of these effects. Rats were divided into 4 groups: sham, l-cysteine, I/R, and l-cysteine- I/R groups. Specimens of sciatic nerve were processed for biochemical, histological, and immunohistochemical assessment. The results showed in I/R group, a significant increase in malondialdehyde with a significant decrease in both Nuclear respiratory factor-1 (NRF1) and superoxide dismutase levels. Moreover, with histological alteration. There was a significant increase in the mean surface area fraction of anti-caspase immunopositive cells as well as a significantdecrease in mean surface area fraction of anti-CD 34 immunopositive cells. In contrast, the l-cysteine- I/R group showed amelioration of these biochemical, structural, and immunohistochemical changes. To the best of our knowledge, this is the first study showed the protective effects of l-cysteine in sciatic nerve I/R via NRF1and caspase 3 modulation as well as telocyte activation.

缺血造成的器官损伤会在再灌注过程中加剧。L- 半胱氨酸是一种半必需氨基酸,是中枢神经系统中胱硫醚-β-合成酶的底物。本研究旨在探讨 L-半胱氨酸对大鼠坐骨神经缺血再灌注(I/R)后发生的结构和生化变化可能具有的保护作用,并探讨这些作用的一些潜在机制。大鼠分为 4 组:假组、L-半胱氨酸组、I/R 组和 L-半胱氨酸-I/R 组。对坐骨神经标本进行生化、组织学和免疫组化评估。结果显示,在 I/R 组中,丙二醛显著增加,核呼吸因子-1(NRF1)和超氧化物歧化酶水平显著下降。此外,组织学也发生了改变。抗天冬酶免疫阳性细胞的平均表面积比例明显增加,抗 CD 34 免疫阳性细胞减少。相比之下,L-半胱氨酸-I/R 组的这些生化、结构和免疫组化变化有所改善。据我们所知,这是首次有研究表明 L-半胱氨酸通过 NRF1 和 caspase 3 调节以及端粒细胞活化对坐骨神经 I/R 有保护作用。
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引用次数: 0
Oxytocin-receptor-expressing neurons in the lateral parabrachial nucleus activate widespread brain regions predominantly involved in fluid satiation 外侧腋旁核中表达催产素受体的神经元能激活主要参与液体饱和的广泛脑区
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-03-06 DOI: 10.1016/j.jchemneu.2024.102403
Janine C.M. Jaramillo , Connor M. Aitken , Andrew J. Lawrence , Philip J. Ryan

Fluid satiation is an important signal and aspect of body fluid homeostasis. Oxytocin-receptor-expressing neurons (OxtrPBN) in the dorsolateral subdivision of the lateral parabrachial nucleus (dl LPBN) are key neurons which regulate fluid satiation. In the present study, we investigated brain regions activated by stimulation of OxtrPBN neurons in order to better characterise the fluid satiation neurocircuitry in mice. Chemogenetic activation of OxtrPBN neurons increased Fos expression (a proxy marker for neuronal activation) in known fluid-regulating brain nuclei, as well as other regions that have unclear links to fluid regulation and which are likely involved in regulating other functions such as arousal and stress relief. In addition, we analysed and compared Fos expression patterns between chemogenetically-activated fluid satiation and physiological-induced fluid satiation. Both models of fluid satiation activated similar brain regions, suggesting that the chemogenetic model of stimulating OxtrPBN neurons is a relevant model of physiological fluid satiation. A deeper understanding of this neural circuit may lead to novel molecular targets and creation of therapeutic agents to treat fluid-related disorders.

体液饱和是体液平衡的一个重要信号和方面。外侧腋旁核背外侧亚区(dl LPBN)的催产素受体表达神经元(OxtrPBN)是调节体液饱和度的关键神经元。在本研究中,我们调查了刺激 OxtrPBN 神经元所激活的脑区,以更好地描述小鼠体液饱和神经回路的特征。对 OxtrPBN 神经元的化学激活增加了已知体液调节脑核的 Fos 表达(神经元激活的替代标记物),也增加了与体液调节联系不明确的其他区域的表达,这些区域很可能参与了唤醒和压力缓解等其他功能的调节。此外,我们还分析并比较了化学激活的体液饱和与生理诱导的体液饱和之间的 Fos 表达模式。两种体液饱和模型激活的脑区相似,这表明刺激 OxtrPBN 神经元的化学遗传模型是生理性体液饱和的相关模型。深入了解这一神经回路可能会发现新的分子靶点,并创造出治疗流体相关疾病的药物。
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引用次数: 0
The neuroprotective effects of baobab and black seed on the rat hippocampus exposed to a 900-MHz electromagnetic field 猴面包树和黑籽对暴露于900兆赫电磁场的大鼠海马神经的保护作用
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-03-04 DOI: 10.1016/j.jchemneu.2024.102405
Hamza Mohamed , Omur Gulsum Deniz , Suleyman Kaplan

This study investigated the potential effects on the hippocampus of electromagnetic fields (EMFs) disseminated by mobile phones and the roles of baobab (Adansonia digitata) (AD) and black seed (Nigella sativa) (BS) in mitigating these. Fifty-six male, 12-week-old Wistar albino rats were divided into eight groups of seven animals each. No EMF exposure was applied to the control, AD or BS groups, while the rats in the Sham group were placed in an EMF system with no exposure. A 900-MHz EMF was applied to the EMF+AD, EMF+BS, EMF+AD+BS and EMF groups for 1 hour a day for 28 days. Pyramidal neurons in the hippocampus were subsequently counted using the optical fractionator technique, one of the unbiased stereological methods. Tissue sections were also evaluated histopathologically under light and electron microscopy. The activities of the enzymes catalase (CAT) and superoxide dismutase (SOD) were also determined in blood serum samples. Analysis of the stereological data revealed no statistically significant differences between the EMF and control or sham groups in terms of pyramidal neuron numbers (p>0.05). However, stereological examination revealed a crucial difference in the entire hippocampus between the control group and the AD (p<0.01) and BS (p<0.05) groups. Moreover, exposure to 900-MHz EMF produced adverse changes in the structures of neurons at histopathological analysis. Qualitative examinations suggest that a combination of herbal products such as AD and BS exerts a protective effect against such EMF side-effects.

本研究调查了移动电话传播的电磁场(EMF)对海马的潜在影响,以及猴面包树(Adansonia digitata)(AD)和黑种草(Nigella sativa)(BS)在减轻这些影响方面的作用。56 只 12 周大的雄性 Wistar 白化大鼠被分成 8 组,每组 7 只。对照组、AD 组和 BS 组不接触电磁场,而 Sham 组的大鼠则被放置在一个不接触电磁场的系统中。对EMF+AD组、EMF+BS组、EMF+AD+BS组和EMF组施加900兆赫的电磁场,每天1小时,持续28天。随后使用无偏立体学方法之一的光学分型器技术对海马中的锥体神经元进行计数。组织切片也在光镜和电子显微镜下进行了组织病理学评估。此外,还测定了血清样本中过氧化氢酶(CAT)和超氧化物歧化酶(SOD)的活性。立体学数据分析显示,就锥体神经元数量而言,EMF 组与对照组或假神经元组之间没有显著的统计学差异(P>0.05)。然而,立体学检查显示,对照组和 AD 组在整个海马体上存在关键性差异(p
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引用次数: 0
Curcumin abrogates cobalt-induced neuroinflammation by suppressing proinflammatory cytokines release, inhibiting microgliosis and modulation of ERK/MAPK signaling pathway 姜黄素通过抑制促炎细胞因子的释放、抑制小胶质细胞增生和调节ERK/MAPK信号通路来减轻钴诱导的神经炎症。
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-02-28 DOI: 10.1016/j.jchemneu.2024.102402
Rademene S. Oria , Godson E. Anyanwu , Johnson N. Nto , James O. Ikpa

Curcumin, a bioactive polyphenol derived from turmeric, has been reported to have anti-inflammatory properties. The current study investigated the anti-inflammatory effect of curcumin in the hippocampal subfields (CA1 and CA3) after exposure to cobalt (Co) and the impact of ERK protein. Twenty-eight albino Wistar rats were divided into four groups, each with seven randomly selected rats as follows: Control (distilled water), Cobalt (Co) only (40 mg/kg), 120 mg/kg or 240 mg/kg curcumin + Co (40 mg/kg). Treatment was via oral gavage for 28 days. We performed a biochemical investigation to determine the levels of proinflammatory cytokines (TNFα and IL-1β). Furthermore, we conducted an immunohistochemical evaluation to assess the expression of IBA1 by microglial cells and the immunoexpression of ERK protein in the hippocampus. Results revealed a significant (p<0.05) elevation in the tissue level of TNFα and IL-1β, an increase in the number of IBA1-positive microglia, and upregulation of ERK protein in the hippocampal subfields of the rats after exposure to cobalt-only. Nevertheless, pretreatment with curcumin restored these parameters to levels comparable to control. In conclusion, our results showed that curcumin abrogated the Co-induced neuroinflammation by suppressing the release of proinflammatory biomarkers, reducing microgliosis, and modulating the ERK/MAPK pathway.

姜黄素是从姜黄中提取的一种生物活性多酚,据报道具有抗炎特性。本研究探讨了姜黄素在暴露于钴(Co)后对海马亚区(CA1和CA3)的抗炎作用以及对ERK蛋白的影响。28 只白化 Wistar 大鼠被分为四组,每组随机抽取 7 只,具体如下:对照组(蒸馏水)、仅钴(Co)组(40 毫克/千克)、姜黄素 + Co(40 毫克/千克)组(120 毫克/千克或 240 毫克/千克)。治疗采用口服灌胃法,为期 28 天。我们进行了生化调查,以确定促炎细胞因子(TNFα和IL-1β)的水平。此外,我们还进行了免疫组化评估,以评估小胶质细胞中 IBA1 的表达以及海马中 ERK 蛋白的免疫表达。结果显示,暴露于纯钴后,大鼠组织中 TNFα 和 IL-1β 水平明显升高(p<0.05),IBA1 阳性小胶质细胞数量增加,海马亚场中 ERK 蛋白上调。然而,姜黄素预处理可使这些参数恢复到与对照组相当的水平。总之,我们的研究结果表明,姜黄素通过抑制促炎生物标志物的释放、减少小胶质细胞增生和调节ERK MAPK通路,减轻了钴诱导的神经炎症。
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引用次数: 0
Protective effects of myricetin and morin on neurological damage in Aβ1–42/Al3+ -induced Alzheimer’s disease model of rats 杨梅素和桑黄对 Aβ1-42/Al3+ 诱导的阿尔茨海默病模型大鼠神经损伤的保护作用
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-02-27 DOI: 10.1016/j.jchemneu.2024.102404
Linli Guo , Yanan Zhao , Zhengqiao Kong , Ruihua Liu , Ping Liu

Alzheimer's disease (AD) is a degenerative neurological disorder with unclear pathogenesis. Single-target drugs have very limited efficacy in treating AD, but synthetic multi-target drugs have poor efficacy and safety. Therefore, finding suitable natural multi-target drugs against AD is of great interest for research studies. We chose two flavonols, myricetin and morin, for the relevant study. In this study, we used microinjection of Aβ1–42 oligomers into the CA1 region of rat hippocampus, combined with gavage of Aluminum chloride hexahydrate (AlCl3·6H2O) solution to establish AD rat models, and myricetin and morin were selected as intervening drugs to explore the protective effects against neurological impairment. Experimental results showed that myricetin or morin could reduce the production of Aβ, Tubulin-associated unit (Tau), and Phosphorylated tubulin-associated unit (p-Tau), down-regulate the expression of relevant inflammatory factors, reduce hippocampal cell apoptosis in rats. There was a significant increase in the activity of adenosine triphosphatase, catalase, total superoxide dismutase, and the content of glutathione in the brain tissue. However, the content of malondialdehyde, inducible nitric oxide synthase, and the activity of acetylcholinesterase were decreased in the brain tissue. These two flavonols can regulate the imbalance of monoamine and amino acid neurotransmitter levels. In conclusion, Myricetin or morin can effectively improve learning and memory dysfunction in AD rats induced by Aβ1–42/Al3+ through anti-oxidative stress and anti-apoptotic features.

阿尔茨海默病(AD)是一种神经系统退行性疾病,发病机制尚不清楚。单靶点药物治疗阿尔茨海默病的疗效非常有限,而合成的多靶点药物疗效和安全性都很差。因此,寻找合适的天然多靶点药物来治疗注意力缺失症是一项非常有意义的研究。我们选择了两种黄酮醇,即 myricetin 和 morin,进行相关研究。在这项研究中,我们采用向大鼠海马 CA1 区显微注射 Aβ1-42 低聚物,并结合灌胃六水氯化铝(AlCl3-6H2O)溶液的方法建立了 AD 大鼠模型,并选择了杨梅素和吗啉作为干预药物,以探讨它们对神经损伤的保护作用。实验结果表明,制霉菌素和吗啉能减少大鼠脑内Aβ、Tau和磷酸化Tau的产生,下调相关炎症因子的表达,减少海马细胞凋亡。脑组织中三磷酸腺苷酶、过氧化氢酶、总超氧化物歧化酶的活性和谷胱甘肽的含量都有明显提高。然而,脑组织中丙二醛的含量、诱导型一氧化氮合酶和乙酰胆碱酯酶的活性则有所下降。这两种黄酮可以调节单胺和氨基酸神经递质水平的失衡。总之,杨梅素或吗啉可通过抗氧化应激和抗细胞凋亡功能有效改善 Aβ1-42/Al3+ 诱导的 AD 大鼠的学习和记忆功能障碍。
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引用次数: 0
Elderberry diet enhances motor performance and reduces neuroinflammation-induced cell death in cerebellar ataxia rat models 接骨木果实饮食可提高小脑共济失调大鼠模型的运动能力,并减少神经炎症引起的细胞死亡。
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-02-23 DOI: 10.1016/j.jchemneu.2024.102399
Maryam Raoofi nejad , Elham Siasi , Mohammad Amin Abdollahifar , Abbas Aliaghaei

Cerebellar ataxia (CA) is a condition in which cerebellar dysfunction results in movement disorders such as dysmetria, synergy and dysdiadochokinesia. This study investigates the therapeutic effects of elderberry (EB) diet on the 3-acetylpyridine-induced (3-AP) CA rat model. First, CA rat models were generated by 3-AP administration followed by elderberry diet treatment containing 2 % EB for 8 consecutive weeks. Motor performance, electromyographic activity and gene expression were then evaluated. The number of Purkinje neurons were evaluated by stereological methods. Immunohistochemistry for the microgliosis, astrogliosis and apoptosis marker caspase-3 was also performed. In addition, the morphology of microglia and astrocytes was assessed using the Sholl analysis method. The results showed that EB diet administration in a 3-AP ataxia model improved motor coordination, locomotor activity and neuro-muscular function, prevented Purkinje neurons degeneration, increased microglia and astrocyte complexity and reduced cell soma size. Moreover, EB diet administration decreased apoptosis in cerebellum of 3-AP ataxic model. In addition, elderberry diet treatment decreased the expression of inflammatory, apoptotic and necroptotic genes and increased the expression of antioxidant-related genes. The results suggest that the EB diet attenuates 3-AP-induced neuroinflammation leading to cell death and improves motor performance. Thus, the EB diet could be used as a therapeutic procedure for CA due to its neuroprotective effects.

小脑共济失调(CA)是一种由小脑功能障碍导致运动障碍的疾病,如构图障碍、协同障碍和运动障碍。本研究探讨了接骨木果(EB)饮食对 3-乙酰基吡啶诱导的 CA 大鼠模型的治疗作用。首先,给大鼠服用 3-AP 后,再用含 2% EB 的接骨木果实饮食连续治疗 8 周,从而建立 CA 大鼠模型。然后对大鼠的运动表现、肌电图活动和基因表达进行评估。通过立体学方法评估了Purkinje神经元的数量。还对小胶质细胞、星形胶质细胞和细胞凋亡标志物 caspase-3 进行了免疫组化。此外,还使用 Sholl 分析方法评估了小胶质细胞和星形胶质细胞的形态。结果表明,在 3-AP 共济失调模型中服用 EB 可改善运动协调性、运动活性和神经肌肉功能,防止浦肯野神经元变性,增加小胶质细胞和星形胶质细胞的复杂性并缩小细胞体大小。此外,接骨木果实饮食还能减少 3-AP 共济失调模型小脑的细胞凋亡。此外,接骨木果实饮食还能减少炎症、凋亡和坏死基因的表达,增加抗氧化相关基因的表达。这些结果表明,接骨木果实饮食可减轻 3-AP 诱导的导致细胞死亡的神经炎症,并改善运动能力。因此,EB饮食具有神经保护作用,可用作CA的治疗方法。
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引用次数: 0
Investigating the impact of nutritional insufficiency on parahippocampal neurons in domestic chickens, Gallus gallus domesticus 研究营养不足对家鸡海马旁神经元的影响
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-02-20 DOI: 10.1016/j.jchemneu.2024.102401
Adarsh Kumar , Kavita Tamta , Hemlata Arya , Shweta Arya , Ram Chandra Maurya

Over time, scientists have been fascinated by the complex connections among nutrition, brain development, and behavior. It's been well understood that the brain's peak performance relies on having the right nutrients available. Thus, nutritional insufficiency, where an organism lacks vital nutrients crucial for optimal growth and function, can upset the body's balance, potentially triggering stress responses. However, our grasp of how the brain reacts to insufficient nutrition, particularly in avian species like domestic chickens, has shown inconsistencies in our understanding. Domestic chickens have frequently served as subjects for studying memory and learning, primarily focusing on the hippocampus—a region highly responsive to environmental changes. Yet, another critical brain region, the parahippocampal region, integral to memory and spatial cognition, had received relatively little attention concerning the consequences of inadequate nutrition and hydration. To address this knowledge gap, our study sought to investigate the impact of stress induced by nutritional insufficiency on the neuronal cells within the region parahippocampalis in two distinct age groups of domestic chickens, Gallus gallus domesticus: fifteen and thirty days old. We employed the Golgi-Cox-Impregnation technique to explore whether the structural characteristics of neuronal cells, specifically the dendritic spines, underwent changes under transient stressful conditions during these crucial developmental stages. The results were intriguing. Stress evidently induced observable alterations in the dendritic spines of the parahippocampal neuronal cells, with the extent of these changes being age-dependent. In fifteen-day-old chickens, stress prompted substantial modifications in the dendritic spines of parahippocampal multipolar and pyramidal neurons. In contrast, among thirty-day-old chickens, the response to stress was less comprehensive, with only specific parahippocampal multipolar neurons displaying such alterations. These findings underscored the influential role of stress in reshaping the structure of parahippocampal neurons and emphasized the importance of considering age when studying the impact of stress on the brain. Through this research, we aim to enhance our understanding of the intricate interplay between stress, brain structure, and the critical role of adequate nutrition, especially during pivotal developmental stages. Our future research objectives include a deeper investigation into the intracellular events including cellular and molecular mechanisms precipitating these changes and determining whether these alterations have downstream effects on crucial brain functions like learning and memory.

长期以来,科学家们一直对营养、大脑发育和行为之间的复杂联系着迷。人们已经清楚地认识到,大脑的最佳表现有赖于适当的营养。因此,营养不足,即机体缺乏对最佳生长和功能至关重要的营养物质,会破坏机体平衡,可能引发应激反应。然而,我们对大脑如何对营养不足做出反应的了解并不一致,尤其是在家鸡等禽类物种中。家鸡经常作为研究记忆和学习的对象,主要集中在海马区--一个对环境变化高度敏感的区域。然而,另一个与记忆和空间认知密不可分的关键脑区--海马旁区--在营养和水分不足的后果方面受到的关注却相对较少。为了填补这一知识空白,我们的研究试图调查营养不足引起的应激对两个不同年龄组(15 天龄和 30 天龄)家鸡海马旁区域神经细胞的影响。我们采用了高尔基-考克斯浸渍技术来探讨在这些关键的发育阶段,神经元细胞的结构特征,特别是树突棘,是否会在短暂的应激条件下发生变化。研究结果耐人寻味。应激明显诱导了海马旁神经元细胞树突棘发生可观察到的变化,这些变化的程度与年龄有关。在 15 日龄的鸡中,应激导致海马旁多极神经元和锥体神经元的树突棘发生显著变化。相比之下,三十天龄的鸡对应激的反应不那么全面,只有特定的海马旁多极神经元显示出这种变化。这些发现强调了应激在重塑海马旁神经元结构中的影响作用,并强调了在研究应激对大脑的影响时考虑年龄因素的重要性。通过这项研究,我们希望进一步了解压力、大脑结构之间错综复杂的相互作用,以及充足营养的关键作用,尤其是在关键的发育阶段。我们未来的研究目标包括更深入地调查细胞内事件,包括引发这些变化的细胞和分子机制,并确定这些变化是否会对学习和记忆等关键大脑功能产生下游影响。
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引用次数: 0
Spexin and nesfatin-1-expressing neurons in the male human claustrum 雄性人耳廓中表达 Spexin 和 nesfatin-1 的神经元。
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-02-09 DOI: 10.1016/j.jchemneu.2024.102400
Artur Pałasz , Anna Lipiec-Borowicz , Aleksandra Suszka-Świtek , Julia Kistowska , Petra Horká , Andrzej Kaśkosz , Aneta Piwowarczyk-Nowak , John J. Worthington , Kinga Mordecka-Chamera

Neuropeptides are involved in numerous brain activities being responsible for a wide spectrum of higher mental functions. The purpose of this concise, structural and qualitative investigation was to map the possible immunoreactivity of the novel regulatory peptides: spexin (SPX) and nesfatin-1 within the human claustrum. SPX is a newly identified peptide, a natural ligand for the galanin receptors (GALR) 2/3, with no molecular structure similarities to currently known regulatory factors. SPX seems to have multiple physiological functions, with an involvement in reproduction and food-intake regulation recently revealed in animal studies. Nesfatin-1, a second pleiotropic neuropeptide, which is a derivative of the nucleobindin-2 (NUCB-2) protein, is characterized by a wide distribution in the brain. Nesfatin-1 is a substance with a strong anorexigenic effect, playing an important role in the neuronal circuits of the hypothalamus that regulate food intake and energy homeostasis. On the other hand, nesfatin-1 may be involved in several important brain functions such as sleep, reproductive behaviour, cognitive processes, stress responses and anxiety. For the first time we detected and described a population of nesfatin-1 and SPX expressing neurons in the human claustrum using immunohistochemical and fluorescent methods. The study presents the novel identification of SPX and nesfatin-1 immunopositive neurons in the human claustrum and their assemblies show similar patterns of distribution in the whole structure.

神经肽参与多种脑部活动,负责多种高级精神功能。这项简明、结构性和定性研究的目的是绘制新型调节肽--spexin(SPX)和nesfatin-1在人体鼓室内可能存在的免疫活性图。SPX是一种新发现的多肽,是加兰宁受体(GALR)2/3的天然配体,其分子结构与目前已知的调节因子没有相似之处。SPX 似乎具有多种生理功能,最近在动物实验中发现它参与生殖和食物摄取调节。Nesfatin-1是第二种多效神经肽,它是核宾蛋白-2(NUCB-2)的衍生物,在大脑中分布广泛。Nesfatin-1 是一种具有强烈厌食作用的物质,在调节食物摄入和能量平衡的下丘脑神经元回路中发挥着重要作用。另一方面,nesfatin-1 可能参与多种重要的大脑功能,如睡眠、生殖行为、认知过程、应激反应和焦虑。我们首次使用免疫组化和荧光方法检测并描述了人耳廓中表达内司蛋白-1和SPX的神经元群。这项研究新颖地发现了人耳蜗中 SPX 和 nesfatin-1 免疫阳性神经元,它们的集合体在整个结构中显示出相似的分布模式。
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引用次数: 0
The protective effect of methanolic extract of Verbascum cheiranthifolium and Biebersteinia multifida DC on hippocampus damage induced by diazinon in male Wistar rats: An experimental study Verbascum cheiranthifolium 和 Biebersteinia multifida DC 的甲醇提取物对重氮农诱导的雄性 Wistar 大鼠海马损伤的保护作用:一项实验研究。
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-02-09 DOI: 10.1016/j.jchemneu.2024.102398
Amir Delavar , Fatemeh Rahimi Anbarkeh , Raheleh Baradaran , Zohreh Arab , Seyed Hamidreza Rastegar Moghaddam , Mahmoud Hosseini , Mohammad Reza Nikravesh , Shahin Saeidi Nejat , Mehdi Jalali

Diazinon (DZN) an organophosphate (OP), with the most important mechanism of action of DZN being induction of oxidative stress (OS) and inhibition of the enzyme acetylcholinesterase (AChE). Verbascum cheiranthifolium (VER) and Biebersteinia multifida (BM) belong to the Scrophulariaceae and Biebersteiniaceae family respectively. These plants are widely used in Iranian traditional medicine due to their beneficial effects. Thus, this research aimed to appraise the protective effects of the methanolic extract of the VER and BM on changes in the level of expression of α7 and α4 subunits of nicotinic acetylcholine receptors (nAChRs) in hippocampus (HPC) of DZN-treated rats. In this research, 36 male Wistar rats were used and randomly divided into six groups: Control, DZN (40 mg/kg), VER (1 g/kg), DZN+VER (40 mg/kg+1 g/kg), BM (150 mg/kg), and DZN+BM (40 mg/kg+150 mg/kg). At the end of treatment periods, the animals of all groups underwent the Morris water maze (MWM) test. The rats were anesthetized, and blood sampling was performed. Eventually, the brain was removed for histological study and evaluation of OS parameters. The results indicated that DZN increased the extent of expression of nAChRs in the HPC and significantly inhibited cholinesterase (ChEs) activity plus OS parameters. Also, in MWM, the time to find the platform was significantly longer in the DZN group, while the time and the distance in the probe test were lower than in the control groups. VER and BM extract in the treatment groups simultaneously improved the extent of expression of nAChRs, ChEs activity, as well as the parameters of OS and spatial memory significantly. In conclusion, our results support the neuroprotective properties of VER and BM extract versus DZN in rats. Accordingly, the extracts of VER and BM may be useful as an approach for the treatment of learning disorders and memory enhancement.

二嗪农(DZN)是一种有机磷(OP),其最重要的作用机制是诱导氧化应激(OS)和抑制乙酰胆碱酯酶(AChE)。Verbascum cheiranthifolium(VER)和 Biebersteinia multifida(BM)分别属于 Scrophulariaceae 和 Biebersteiniaceae 科。这些植物因其有益功效而在伊朗传统医学中被广泛使用。因此,本研究旨在评估 VER 和 BM 的甲醇提取物对 DZN 治疗大鼠海马(HPC)中烟碱乙酰胆碱受体(nAChRs)α7 和 α4 亚基表达水平变化的保护作用。本研究使用了 36 只雄性 Wistar 大鼠,并将其随机分为六组:对照组、DZN(40mg/kg)组、VER(1g/kg)组、DZN+VER(40mg/kg+1g/kg)组、BM(150mg/kg)组和DZN+BM(40mg/kg+150mg/kg)组。治疗结束后,各组动物均进行莫里斯水迷宫(MWM)试验。对大鼠进行麻醉并抽血。最后,取出大鼠大脑进行组织学研究并评估操作系统参数。结果表明,DZN 增加了 HPC 中 nAChRs 的表达量,并显著抑制了胆碱酯酶(ChEs)活性和 OS 参数。此外,在 MWM 中,DZN 组找到平台的时间明显长于对照组,而探针测试的时间和距离则低于对照组。治疗组中的 VER 和 BM 提取物同时显著改善了 nAChRs 的表达程度、ChEs 活性以及 OS 和空间记忆的参数。总之,我们的研究结果支持 VER 和 BM 提取物相对于 DZN 对大鼠神经的保护作用。因此,VER 和 BM 的提取物可作为治疗学习障碍和增强记忆的一种有用方法。
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引用次数: 0
Tetrahydropiperine, a natural alkaloid with neuroprotective effects in ischemic stroke 四氢哌啶--一种对缺血性中风具有神经保护作用的天然生物碱
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-02-07 DOI: 10.1016/j.jchemneu.2024.102397
Hongyan Ren , Qianqian Yuan , Jiayuan Lu , Siyu Xi , Yanbo Liu , Guangyu Yang , Zhixi Xie , Bo Wang , Li Ma , Xueyan Fu , Juan Liu , Yiwei Zhang

Background

Ischemic stroke (IS) is a life-threatening neurological disease with various pathological mechanisms. Tetrahydropiperine (THP) is a natural alkaloid with protective effects against multiple diseases, such as seizure, and pain. This study was to examine the impact of THP on IS and investigate its potential mechanism.

Material and methods

We employed network pharmacology and molecular docking techniques to identify the target proteins of THP for intervention in IS. Adult male Sprague-Dawley rats were used to create a permanent middle cerebral artery occlusion model. PC-12 cells were chosen to establish an oxygen–glucose deprivation (OGD) cell model. Disease modeling followed by nimodipine (NIMO); 3-methyladenine (3-MA) and rapamycin (RAP) interventions. Open field test, Longa score, balance beam test, and forelimb grip test were used to measure motor and neurological functions. The degree of neurological damage recovery was assessed through behavioral analysis, and cerebral infarction volume was determined using TTC staining. Morphological changes were examined through HE and Nissl staining, and ultrastructural changes in neurons were observed using transmission electron microscopy. The protein expression of autophagy and related pathways was analyzed through Western blot (WB). The appropriate hypoxia time and drug concentration were determined using CCK-8 assay, which also measured cell survival rate.

Results

The network pharmacology findings indicated that the impact of THP on IS was enhanced in the PI3K/Akt signaling pathway. THP demonstrated robust docking capability with proteins associated with the autophagy and PI3K/Akt/mTOR, as indicated by the molecular docking outcomes. THP significantly improved behavioral damage, reduced the area of cerebral infarction, ameliorated histopathological damage from ischemia, increase neuronal survival, and alleviated ultrastructural damage in neurons (P < 0.05). THP enhanced the survival of PC-12 cells induced by OGD and ameliorated the morphological harm to the cells (P < 0.05). THP was found to elevate the quantities of P62, LC3-Ⅰ, PI3K, P-AKt/Akt, and P-mTOR/mTOR proteins while reducing the levels of Atg7 and Beclin1 proteins. The results of transmission electron microscopy showed no autophagosomes in the THP, 3-MA, and 3-MA + THP groups.

Conclusion

The activation of the PI3K/Akt/mTOR signaling pathway by THP inhibits autophagy and provides relief from neurological damage in IS.

背景:缺血性中风(IS)是一种危及生命的神经系统疾病,其病理机制多种多样。四氢哌啶(THP)是一种天然生物碱,对癫痫、疼痛等多种疾病具有保护作用。本研究旨在探讨 THP 对 IS 的影响,并研究其潜在机制:我们采用网络药理学和分子对接技术来确定 THP 干预 IS 的靶蛋白。用成年雄性 Sprague-Dawley 大鼠建立永久性大脑中动脉闭塞模型。选择 PC-12 细胞建立氧-葡萄糖剥夺(OGD)细胞模型。疾病建模后进行尼莫地平(NIMO)、3-甲基腺嘌呤(3-MA)和雷帕霉素(RAP)干预。采用开阔地测试、Longa评分、平衡木测试和前肢握力测试来测量运动和神经功能。通过行为分析评估神经损伤的恢复程度,并使用 TTC 染色测定脑梗塞体积。通过 HE 和 Nissl 染色检查形态学变化,并使用透射电子显微镜观察神经元的超微结构变化。通过 Western 印迹(WB)分析自噬及相关通路的蛋白表达。利用 CCK-8 试验确定了适当的缺氧时间和药物浓度,同时还测定了细胞存活率:网络药理学研究结果表明,在 PI3K/Akt 信号通路中,THP 对 IS 的影响增强。分子对接结果表明,THP 与自噬和 PI3K/Akt/mTOR 相关蛋白的对接能力很强。THP 能明显改善行为损伤,减少脑梗塞面积,改善缺血造成的组织病理学损伤,提高神经元存活率,减轻神经元超微结构损伤(P < 0.05)。THP 可提高 OGD 诱导的 PC-12 细胞的存活率,并改善细胞的形态损伤(P < 0.05)。研究发现,THP能提高P62、LC3-Ⅰ、PI3K、P-AKt/Akt和P-mTOR/mTOR蛋白的数量,同时降低Atg7和Beclin1蛋白的水平。透射电子显微镜结果显示,THP 组、3-MA 组和 3-MA + THP 组均无自噬体:结论:THP激活PI3K/Akt/mTOR信号通路可抑制自噬,缓解IS的神经损伤。
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引用次数: 0
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Journal of chemical neuroanatomy
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