Current Alzheimer research最新文献

Corrigendum to: Upregulation of Suppressor of Cytokine Signaling 3 in Microglia by Cinnamic Acid 更正：肉桂酸对小胶质细胞细胞因子信号转导抑制因子 3 的上调作用

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current Alzheimer research

Pub Date : 2024-09-04 DOI: 10.2174/156720502103240830145259

Sudipta Chakrabarti, Malabendu Jana, Avik Roy, Kalipada Pahan

In the online version of the article, a change was made in Figure 1 of the article titled “Upregulation of Suppressor of Cytokine Signaling 3 in Microglia by Cinnamic Acid”, published in Current Alzheimer Research, 2018, 15(10), 894-904. The author informed the publisher that an incorrect image was provided for Figure 1. The correct image was from the P-CREB experiment of Figure 5 [1]. Now, the revised Figure 1 has been updated in the article, and it can be found online at: https://www.eurekaselect.com/article/90209

在线版本的文章中，题为 "Upregulation of Suppressor of Cytokine Signaling 3 in Microglia by Cinnamic Acid"（肉桂酸对小胶质细胞细胞因子信号转导抑制因子3的上调）的图1有一处改动，发表于《Current Alzheimer Research》，2018，15（10），894-904。作者告知出版商，图1提供的图片有误。正确的图片来自图5的P-CREB实验[1]。 现在，文章中已经更新了修改后的图1，可在线查阅： https://www.eurekaselect.com/article/90209

引用次数: 0

Comprehensive Insights into Pathophysiology of Alzheimer's Disease: Herbal Approaches for Mitigating Neurodegeneration 全面了解阿尔茨海默病的病理生理学：缓解神经变性的草药方法

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current Alzheimer research

Pub Date : 2024-04-16 DOI: 10.2174/0115672050309057240404075003

Debasis Sen, Sunny Rathee, Vishal Pandey, Sanjay K. Jain, Umesh K. Patil

: Alzheimer's disease [AD] is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and functional impairment. Despite extensive research, the exact etiology remains elusive. This review explores the multifaceted pathophysiology of AD, focusing on key hypotheses such as the cholinergic hypothesis, hyperphosphorylated Tau Protein and Amyloid β hypothesis, oxidative stress hypothesis, and the metal ion hypothesis. Understanding these mechanisms is crucial for developing effective therapeutic strategies. Current treatment options for AD have limitations, prompting the exploration of alternative approaches, including herbal interventions. Cholinesterase inhibitors, targeting the cholinergic hypothesis, have shown modest efficacy in managing symptoms. Blocking Amyloid β [Aβ] and targeting hyperphosphorylated tau protein are under investigation, with limited success in clinical trials. Oxidative stress, implicated in AD pathology, has led to the investigation of antioxidants. Natural products, such as Punica granatum Linn, Radix Scutellariae, and Curcuma longa have demonstrated antioxidant properties, along with anti-inflammatory effects, offering potential neuroprotective benefits. Several herbal extracts, including Ginkgo biloba, Bacopa monnieri, and Withania somnifera, have shown promise in preclinical studies. Compounds like Huperzine A, Melatonin, and Bryostatin exhibit neuroprotective effects through various mechanisms, including cholinergic modulation and anti-inflammatory properties. However, the use of herbal drugs for AD management faces limitations, including standardization issues, variable bioavailability, and potential interactions with conventional medications. Additionally, the efficacy and safety of many herbal products remain to be established through rigorous clinical trials. This review also highlights promising natural products currently in clinical trials, such as Resveratrol and Homotaurine, and their potential impact on AD progression. DHA, an omega-3 fatty acid, has shown cognitive benefits, while Nicotine is being explored for its neuroprotective effects. In conclusion, a comprehensive understanding of the complex pathophysiology of AD and the exploration of herbal interventions offer a holistic approach to managing this devastating disease. Future research should address the limitations associated with herbal drugs and further evaluate the efficacy of promising natural products in clinical settings.

:阿尔茨海默病是一种进行性神经退行性疾病，以认知能力下降、记忆力减退和功能障碍为特征。尽管进行了广泛的研究，但确切的病因仍然难以捉摸。本综述探讨了 AD 的多方面病理生理学，重点关注胆碱能假说、高磷酸化 Tau 蛋白和淀粉样蛋白 β 假说、氧化应激假说和金属离子假说等关键假说。了解这些机制对于制定有效的治疗策略至关重要。目前治疗注意力缺失症的方法存在局限性，这促使人们探索包括草药干预在内的替代方法。针对胆碱能假说的胆碱酯酶抑制剂在控制症状方面显示出一定的疗效。阻断淀粉样蛋白 β [Aβ]和针对高磷酸化 tau 蛋白的药物正在研究中，但在临床试验中成效有限。与注意力缺失症病理有关的氧化应激导致了对抗氧化剂的研究。石榴、黄芩和莪术等天然产品已证明具有抗氧化特性和抗炎作用，可提供潜在的神经保护功效。银杏叶、猴面包树和睡莲等几种草药提取物已在临床前研究中显示出前景。Huperzine A、Melatonin 和 Bryostatin 等化合物通过各种机制（包括胆碱能调节和抗炎特性）显示出神经保护作用。然而，使用草药治疗注意力缺失症面临着一些限制，包括标准化问题、生物利用度不稳定以及与常规药物的潜在相互作用。此外，许多草药产品的疗效和安全性仍有待通过严格的临床试验来确定。本综述还重点介绍了目前正在进行临床试验的白藜芦醇和高牛磺酸等前景看好的天然产品，以及它们对AD进展的潜在影响。欧米伽-3 脂肪酸 DHA 已显示出对认知的益处，而尼古丁的神经保护作用也在探索之中。总之，全面了解注意力缺失症复杂的病理生理学并探索草药干预措施，为控制这种毁灭性疾病提供了一种综合方法。未来的研究应解决与草药相关的局限性，并进一步评估有前景的天然产品在临床环境中的疗效。

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引用次数: 0

Post-Translational Modifications in Tau and Their Roles in Alzheimer's Pathology Tau 的翻译后修饰及其在阿尔茨海默病病理学中的作用

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current Alzheimer research

Pub Date : 2024-04-16 DOI: 10.2174/0115672050301407240408033046

Subha Kalyaanamoorthy, Stanley Kojo Opare, Xiaoxiao Xu, Aravindhan Ganesan, Praveen P.N. Rao

:: Microtubule-Associated Protein Tau (also known as tau) has been shown to accumulate into paired helical filaments and neurofibrillary tangles, which are known hallmarks of Alzheimer’s disease (AD) pathology. Decades of research have shown that tau protein undergoes extensive post-translational modifications (PTMs), which can alter the protein's structure, function, and dynamics and impact the various properties such as solubility, aggregation, localization, and homeostasis. There is a vast amount of information describing the impact and role of different PTMs in AD pathology and neuroprotection. However, the complex interplay between these PTMs remains elusive. Therefore, in this review, we aim to comprehend the key post-translational modifications occurring in tau and summarize potential connections to clarify their impact on the physiology and pathophysiology of tau. Further, we describe how different computational modeling methods have helped in understanding the impact of PTMs on the structure and functions of the tau protein. Finally, we highlight the tau PTM-related therapeutics strategies that are explored for the development of AD therapy.

::微管相关蛋白 Tau（又称 tau）已被证明会积聚成成对螺旋丝和神经纤维缠结，这是已知的阿尔茨海默病（AD）病理特征。数十年的研究表明，tau 蛋白会经历大量的翻译后修饰（PTM），这些修饰会改变蛋白质的结构、功能和动力学，并影响其各种特性，如溶解性、聚集性、定位和稳态。有大量信息描述了不同的 PTMs 在艾滋病病理和神经保护中的影响和作用。然而，这些 PTM 之间复杂的相互作用仍然难以捉摸。因此，在这篇综述中，我们旨在理解发生在 tau 中的关键翻译后修饰，并总结其潜在联系，以阐明它们对 tau 生理和病理生理学的影响。此外，我们还介绍了不同的计算建模方法如何帮助理解 PTM 对 tau 蛋白结构和功能的影响。最后，我们重点介绍了为开发注意力缺失症疗法而探索的 tau PTM 相关治疗策略。

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引用次数: 0

The Postoperative Effects of Anesthesia Exposure on Cognitive Decline in Older Adults: A Narrative Review 麻醉暴露对老年人认知能力下降的术后影响：叙述性综述

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current Alzheimer research

Pub Date : 2024-04-16 DOI: 10.2174/0115672050288199240408035201

Kathleen Angela Willoughby-Dudley, Marielle L. Darwin, Deana B. Davalos

Background:: As modern medicine continues to make strides in effective surgical treatments, we must also consider the critical impact of anesthesia on neuropsychological outcomes. Recent evidence suggests that anesthesia exposure may be a risk factor for postoperative cognitive decline and the eventual development of dementia. Objectives:: To explore the vulnerability of the aging brain in the context of anesthesia exposure in surgery, studies will be reviewed, and pertinent findings will be highlighted and explored to better understand risks and possible factors that need to be considered when contemplating surgery. Methods: A narrative review was conducted using a combination of MEDLINE and APA PsycINFO databases to shed light on themes across studies assessing general trends regarding the influence of anesthesia on postoperative cognitive decline. Results:: A search of relevant literature identified 388 articles. Excluding results outside the parameters of this study, the review includes quality assessments for 24 articles. Conclusion:: While findings are inconclusive, suggestions for further investigation into the relationship between anesthesia exposure and increased risk for postoperative cognitive decline are discussed, in addition to factors that may allow for greater informed disclosure of potential risks of anesthesia in older adults.

背景随着现代医学在有效手术治疗方面不断取得进步，我们也必须考虑麻醉对神经心理学结果的重要影响。最近的证据表明，麻醉暴露可能是导致术后认知能力下降并最终发展为痴呆症的风险因素。研究目的为了探索老化大脑在手术麻醉暴露中的脆弱性，我们将回顾相关研究，并强调和探讨相关发现，以便更好地了解风险以及在考虑手术时需要考虑的可能因素。方法：结合使用 MEDLINE 和 APA PsycINFO 数据库进行了叙述性综述，以阐明各项研究的主题，评估麻醉对术后认知能力下降影响的总体趋势。结果对相关文献的检索发现了 388 篇文章。排除本研究参数之外的结果，综述包括对 24 篇文章的质量评估。结论虽然研究结果尚无定论，但讨论了进一步调查麻醉暴露与术后认知能力下降风险增加之间关系的建议，以及允许在更知情的情况下披露老年人麻醉潜在风险的因素。

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引用次数: 0

Evaluation and Characterization of Modified K114 Method to Localize Plaques in Rodent and Plaques and Tangles in Human Brain Tissue 评估和表征用于定位啮齿动物斑块和人类脑组织中斑块与纠结的改良 K114 方法

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current Alzheimer research

Pub Date : 2024-04-03 DOI: 10.2174/0115672050295561240327055835

Sanjana Padala, Sharay Setti, James Raymick, Joseph Hanig, Sumit Sarkar

Background: A plethora of studies has shown the utility of several chemical dyes due to their affinity to bind Aβ to enable visualization of plaques under light or fluorescence microscope, and some of them showed affinity to bind neurofibrillary tangles (NFT) as well. However, only a few of them have the propensity to bind both senile plaques (SP) and NFT simultaneously. Objective: In our current study, we aimed to modify the K114 dye and the staining procedure to substantially improve the staining of amyloid plaques in both human and rodent brains and neurofibrillary tangles in the human brain Methods: We modified the K114 solution and the staining procedure using Sudan Black as a modifier. Additionally, to evaluate the target of the modified K114, we performed double labeling of K114 and increased Aβ against three different epitopes. We used 5 different antibodies to detect phosphorylated tau to understand the specific targets that modified K114 binds. method: We have modified the K114 solution and the staining procedure using Sudan Black as modifier. Additionally, to evaluate the target of the modified K114, we performed double labeling of K114, and Aβ raised against three different epitopes. We used 5 different antibodies to detect phosphorylated Tau to understand the potential binding targets. Results: Dual labeling using hyperphosphorylated antibodies against AT8, pTau, and TNT1 revealed that more than 80% hyperphosphorylated tau colocalized with tangles that were positive for modified K114, whereas more than 70% of the hyperphosphorylated tau colocalized with modified K114. On the other hand, more than 80% of the plaques that were stained with Aβ MOAB-2 were colocalized with modified K114. result: We have found more than 80% hyperphosphorylated Tau against AT8, PTau and TNT1 colocalized with K114 labeled tangles, whereas more than 70% of the hyperphosphorylated Tau colocalized with modified K114. On the other hand, more than 80% of the plaques that were stained with amyloid beta MOAB-2 were colocalized with modified K114. Conclusion: Our modified method can label amyloid plaques within 5 min in the rat brain and within 20 min in the human brain. Our results indicated that modified K114 could be used as a valuable tool for detecting amyloid plaques and tangles with high contrast and resolution relative to other conventional fluorescence markers.

背景：大量研究表明，几种化学染料能亲和性地结合 Aβ，从而在光镜或荧光显微镜下观察斑块，其中一些染料还能亲和性地结合神经纤维缠结（NFT）。然而，只有少数几种药物具有同时结合老年斑（SP）和神经纤维缠结（NFT）的倾向。研究目的在目前的研究中，我们旨在改进 K114 染料和染色程序，以大幅提高人脑和啮齿类动物大脑中淀粉样斑块和人脑中神经纤维缠结的染色效果：我们使用苏丹黑作为改良剂，对 K114 溶液和染色程序进行了改良。此外，为了评估改良后 K114 的靶标，我们对 K114 进行了双标记，并增加了针对三种不同表位的 Aβ。我们使用了 5 种不同的抗体来检测磷酸化 tau，以了解修饰后的 K114 结合的特定靶标：我们使用苏丹黑作为改性剂对 K114 溶液和染色过程进行了改良。此外，为了评估修饰 K114 的靶标，我们对 K114 和针对三种不同表位的 Aβ 进行了双重标记。我们使用了 5 种不同的抗体来检测磷酸化的 Tau，以了解潜在的结合靶点。结果：使用针对AT8、pTau和TNT1的高磷酸化抗体进行双重标记发现，80%以上的高磷酸化tau与修饰K114阳性的缠结聚集在一起，而70%以上的高磷酸化tau与修饰K114聚集在一起。另一方面，超过 80% 的用 Aβ MOAB-2 染色的斑块与修饰的 K114 共聚焦：我们发现 80% 以上的针对 AT8、PTau 和 TNT1 的高磷酸化 Tau 与 K114 标记的缠结共聚焦，而 70% 以上的高磷酸化 Tau 与修饰的 K114 共聚焦。另一方面，超过 80% 的淀粉样 beta MOAB-2 染色斑块与修饰的 K114 共聚焦。结论我们改进的方法可在 5 分钟内标记大鼠大脑中的淀粉样蛋白斑块，在 20 分钟内标记人脑中的淀粉样蛋白斑块。我们的研究结果表明，与其他传统荧光标记物相比，改良的 K114 可用作检测淀粉样蛋白斑块和纠结的重要工具，具有高对比度和高分辨率。

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引用次数: 0

Uncovering the Impact of Aggrephagy in the Development of Alzheimer's Disease: Insights Into Diagnostic and Therapeutic Approaches from Machine Learning Analysis 揭示阿尔茨海默病发病过程中的吞噬作用：从机器学习分析中洞察诊断和治疗方法

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current Alzheimer research

Pub Date : 2023-12-23 DOI: 10.2174/0115672050280894231214063023

Jiayu Xu, Siqi Gou, Xueyuan Huang, Jieying Zhang, Xuancheng Zhou, Xiangjin Gong, Jingwen Xiong, Hao Chi, Guanhu Yang

Background:: Alzheimer's disease (AD) stands as a widespread neurodegenerative disorder marked by the gradual onset of memory impairment, predominantly impacting the elderly. With projections indicating a substantial surge in AD diagnoses, exceeding 13.8 million individuals by 2050, there arises an urgent imperative to discern novel biomarkers for AD. Methods:: To accomplish these objectives, we explored immune cell infiltration and the expression patterns of immune cells and immune function-related genes of AD patients. Furthermore, we utilized the consensus clustering method combined with aggrephagy-related genes (ARGs) for typing AD patients and categorized AD specimens into distinct clusters (C1, C2). A total of 272 candidate genes were meticulously identified through a combination of differential analysis and Weighted Gene Co-Expression Network Analysis (WGCNA). Subsequently, we applied three machine learning algorithms-namely random forest (RF), support vector machine (SVM), and generalized linear model (GLM)-to pinpoint a pathogenic signature comprising five genes associated with AD. To validate the predictive accuracy of these identified genes in discerning AD progression, we constructed nomograms. Results:: Our analyses uncovered that cluster C2 exhibits a higher immune expression than C1. Based on the ROC(0.956). We identified five characteristic genes (PFKFB4, PDK3, KIAA0319L, CEBPD, and PHC2T) associated with AD immune cells and function. The nomograms constructed on the basis of these five diagnostic genes demonstrated effectiveness. In the validation group, the ROC values were found to be 0.760 and 0.838, respectively. These results validate the robustness and reliability of the diagnostic model, affirming its potential for accurate identification of AD. Conclusion:: Our findings not only contribute to a deeper understanding of the molecular mechanisms underlying AD but also offer valuable insights for drug development and clinical analysis. The limitation of our study is the limited sample size, and although AD-related genes were identified and some of the mechanisms elucidated, further experiments are needed to elucidate the more in-depth mechanisms of these characterized genes in the disease. result: Our analyses revealed that in the machine learning training group (GSE33000 dataset), the RF, SVM, and GLM models achieved an area under the receiver operating characteristic curve (ROC AUC) values of 0.934, 0.956, and 0.728, respectively. Based on the ROC AUC, we selected the SVM model as our experimental method and identified five characteristic genes associated with AD. The validation group (GSE122063 and GSE109887 datasets) yielded ROC AUC values of 0.760 and 0.838, respectively.

背景阿尔茨海默病（AD）是一种广泛的神经退行性疾病，以逐渐出现记忆障碍为特征，主要影响老年人。据预测，到 2050 年，阿尔茨海默病的诊断人数将大幅增加，超过 1380 万人，因此迫切需要发现阿尔茨海默病的新型生物标志物。研究方法为了实现这些目标，我们研究了 AD 患者的免疫细胞浸润以及免疫细胞和免疫功能相关基因的表达模式。此外，我们利用共识聚类法结合侵袭相关基因（ARGs）对AD患者进行分型，并将AD标本分为不同的群组（C1、C2）。通过差分分析和加权基因共表达网络分析（WGCNA），我们精心确定了272个候选基因。随后，我们应用三种机器学习算法--即随机森林（RF）、支持向量机（SVM）和广义线性模型（GLM）--确定了由五个与AD相关的基因组成的致病特征。为了验证这些已识别基因在鉴别 AD 进展方面的预测准确性，我们构建了提名图。结果我们的分析发现，C2群组的免疫表达高于C1群组。根据 ROC（0.956）。我们发现了五个与 AD 免疫细胞和功能相关的特征基因（PFKFB4、PDK3、KIAA0319L、CEBPD 和 PHC2T）。以这五个诊断基因为基础构建的提名图显示出了有效性。在验证组中，ROC 值分别为 0.760 和 0.838。这些结果验证了诊断模型的稳健性和可靠性，肯定了其准确识别 AD 的潜力。结论我们的研究结果不仅有助于加深对AD分子机制的理解，还为药物开发和临床分析提供了有价值的见解。我们研究的局限性在于样本量有限，虽然发现了AD相关基因并阐明了部分机制，但要阐明这些特征基因在疾病中更深入的机制，还需要进一步的实验：我们的分析表明，在机器学习训练组（GSE33000 数据集）中，RF、SVM 和 GLM 模型的接收者操作特征曲线下面积（ROC AUC）值分别为 0.934、0.956 和 0.728。根据 ROC AUC 值，我们选择 SVM 模型作为实验方法，并确定了与 AD 相关的五个特征基因。验证组（GSE122063 和 GSE109887 数据集）的 ROC AUC 值分别为 0.760 和 0.838。

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引用次数: 0

Interactions of Polyphenolic Gallotannins with Amyloidogenic Polypeptides Associated with Alzheimer’s Disease: From Molecular Insights to Physiological Significance 多酚类五倍子单宁与阿尔茨海默病相关致淀粉样多肽的相互作用：从分子洞察到生理意义

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current Alzheimer research

Pub Date : 2023-12-18 DOI: 10.2174/0115672050277001231213073043

Jihane Khalifa, Steve Bourgault, Roger Gaudreault

: Polyphenols are natural compounds abundantly found in plants. They are known for their numerous benefits to human health, including antioxidant properties and anti-inflammatory activities. Interestingly, many studies have revealed that polyphenols can also modulate the formation of amyloid fibrils associated with disease states and can prevent the formation of cytotoxic oligomer species. In this review, we underline the numerous effects of four hydrolysable gallotannins (HGTs) with high conformational flexibility, low toxicity, and multi-targeticity, e.g., tannic acid, pentagalloyl glucose, corilagin, and 1,3,6-tri-O-galloyl-β-D-glucose, on the aggregation of amyloidogenic proteins associated with the Alzheimer’s Disease (AD). These HGTs have demonstrated interesting abilities to reduce, at different levels, the formation of amyloid fibrils involved in AD, including those assembled from the amyloid β-peptide, the tubulin-associated unit, and the islet amyloid polypeptide. HGTs were also shown to disassemble pre-formed fibrils and to diminish cognitive decline in mice. Finally, this manuscript highlights the importance of further investigating these naturally occurring HGTs as promising scaffolds to design molecules that can interfere with the formation of proteotoxic oligomers and aggregates associated with AD pathogenesis

:多酚是大量存在于植物中的天然化合物。众所周知，它们对人体健康有诸多益处，包括抗氧化特性和抗炎活性。有趣的是，许多研究表明，多酚还能调节与疾病相关的淀粉样纤维的形成，并能防止细胞毒性低聚物的形成。在这篇综述中，我们强调了四种具有高构象灵活性、低毒性和多靶点性的可水解五倍子单宁（HGTs），如单宁酸、五没食子酰葡萄糖、柯里拉京和 1,3,6-三-O-没食子酰-β-D-葡萄糖，对与阿尔茨海默病（AD）相关的淀粉样蛋白聚集的诸多影响。这些 HGTs 在不同程度上减少了与阿尔茨海默病有关的淀粉样纤维的形成，包括由淀粉样β肽、小管蛋白相关单位和胰岛淀粉样多肽组装而成的淀粉样纤维。研究还表明，HGTs 能分解预先形成的纤维，减轻小鼠认知能力的衰退。最后，本手稿强调了进一步研究这些天然存在的 HGTs 的重要性，这些 HGTs 是设计分子的有前途的支架，可以干扰与注意力缺失症发病机制相关的蛋白毒性寡聚体和聚集体的形成。

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引用次数: 0

Caffeine improves memory and cognition via modulating neural progenitor cell survival and decreasing oxidative stress in Alzheimer's rat model. 在阿尔茨海默病大鼠模型中，咖啡因通过调节神经祖细胞存活和降低氧化应激来改善记忆和认知。

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current Alzheimer research

Pub Date : 2023-06-05 DOI: 10.2174/1567205020666230605113856

Virendra Tiwari, Akanksha Mishra, Sonu Singh, Shubha Shukla

Aims: Caffeine possesses potent antioxidant, anti-inflammatory and anti-apoptotic activities against a variety of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). The goal of this study was to investigate the protective role of a psychoactive substance like caffeine on hippocampal neurogenesis and memory functions in streptozotocin (STZ)-induced neurodegeneration in rats.

Background: Caffeine is a natural CNS stimulant, belonging to the methylxanthine class, and is a widely consumed psychoactive substance. It is reported to abate the risk of various abnormalities that are cardiovascular system (CVS) related, cancer related, or due to metabolism dysregulation. Short-term caffeine exposure has been widely evaluated, but its chronic exposure is less explored and pursued. Several studies suggest a devastating role of caffeine in neurodegenerative disorders. However, the protective role of caffeine on neurodegeneration is still unclear.

Objective: Here, we examined the effects of chronic caffeine administration on hippocampal neurogenesis in intracerebroventricular STZ injection induced memory dysfunction in rats. The chronic effect of caffeine on proliferation and neuronal fate determination of hippocampal neurons was evaluated by co-labeling of neurons by thymidine analogue BrdU that labels new born cells, DCX (a marker for immature neurons) and NeuN that labels mature neurons.

Method: STZ (1 mg/kg, 2 μl) was injected stereotaxically into the lateral ventricles (intracerebroventricular injection) once on day 1, followed by chronic treatment with caffeine (10 mg/kg, i.p) and donepezil (5 mg/kg, i.p.). Protective effect of caffeine on cognitive impairment and adult hippocampal neurogenesis was evaluated.

Result: Our findings show decreased oxidative stress burden and amyloid burden following caffeine administration in STZ lesioned SD rats. Further, double immunolabeling with bromodeoxyuridine+/doublecortin+ (BrdU+/DCX+) and bromodeoxyuridine+/ neuronal nuclei+ (BrdU+/NeuN+) has indicated that caffeine improved neuronal stem cell proliferation and long term survival in STZ lesioned rats.

Conclusion: Our findings support the neurogenic potential of caffeine in STZ induced neurodegeneration.

目的:咖啡因对多种神经退行性疾病，包括阿尔茨海默病(AD)和帕金森病(PD)具有有效的抗氧化、抗炎和抗凋亡活性。本研究旨在探讨咖啡因等精神活性物质对链脲佐菌素(STZ)诱导的大鼠海马神经发生和记忆功能的保护作用。背景:咖啡因是一种天然的中枢神经系统兴奋剂，属于甲基黄嘌呤类，是一种广泛使用的精神活性物质。据报道，它可以降低心血管系统(CVS)相关、癌症相关或代谢失调引起的各种异常的风险。短期咖啡因暴露已被广泛评估，但其长期暴露较少探索和追求。几项研究表明，咖啡因在神经退行性疾病中起着毁灭性的作用。然而，咖啡因对神经变性的保护作用仍不清楚。目的:观察慢性咖啡因给药对脑室注射STZ诱导记忆功能障碍大鼠海马神经发生的影响。通过胸苷类似物BrdU(新生细胞的标记物)、DCX(未成熟神经元的标记物)和NeuN(成熟神经元的标记物)共同标记神经元，评估咖啡因对海马神经元增殖和神经元命运决定的慢性影响。方法:将STZ (1 mg/kg, 2 μl)于第1天立体定向注射侧脑室(脑室内注射)1次，随后用咖啡因(10 mg/kg, 1次)和多奈哌齐(5 mg/kg, 1次)慢性治疗。评价了咖啡因对认知障碍和成人海马神经发生的保护作用。结果:我们的研究结果表明，在STZ损伤的SD大鼠中，咖啡因可以降低氧化应激负担和淀粉样蛋白负担。此外，溴脱氧尿苷+/双皮质素+ (BrdU+/DCX+)和溴脱氧尿苷+/神经元核+ (BrdU+/NeuN+)的双重免疫标记表明，咖啡因可改善STZ损伤大鼠的神经干细胞增殖和长期存活。结论:我们的研究结果支持咖啡因在STZ诱导的神经变性中的神经源性潜力。

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引用次数: 1

Effect of APOE4 Allele and Gender on the Rate of Atrophy in the Hippocampus, Entorhinal Cortex, and Fusiform Gyrus in Alzheimer's Disease. APOE4 等位基因和性别对阿尔茨海默病海马、内顶皮层和纺锤形回萎缩速度的影响

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current Alzheimer research

Pub Date : 2023-03-09 DOI: 10.2174/1567205020666230309113749

Eid Abo Hamza, Ahmed A Moustafa, Richard Tindle, Rasu Karki, Shahed Nalla, Mohamed S Hamid, Mohamad El Haj

Background: The hippocampus, entorhinal cortex, and fusiform gyrus are brain areas that deteriorate during early-stage Alzheimer's disease (AD). The ApoE4 allele has been identified as a risk factor for AD development, is linked to an increase in the aggregation of amyloid ß (Aß) plaques in the brain, and is responsible for atrophy of the hippocampal area. However, to our knowledge, the rate of deterioration over time in individuals with AD, with or without the ApoE4 allele, has not been investigated.

Method: In this study, we, for the first time, analyze atrophy in these brain structures in AD patients with and without the ApoE4 using the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset.

Results: It was found that the rate of decrease in the volume of these brain areas over 12 months was related to the presence of ApoE4. Further, we found that neural atrophy was not different for female and male patients, unlike prior studies, suggesting that the presence of ApoE4 is not linked to the gender difference in AD.

Conclusion: Our results confirm and extend previous findings, showing that the ApoE4 allele gradually impacts brain regions impacted by AD.

背景海马、内侧皮层和纺锤形回是阿尔茨海默病（AD）早期恶化的脑区。载脂蛋白E4等位基因已被确定为阿尔茨海默病发病的风险因素，与大脑中淀粉样蛋白ß（Aß）斑块聚集的增加有关，并导致海马区萎缩。然而，据我们所知，目前还没有人研究过带有或不带有载脂蛋白E4等位基因的AD患者随着时间推移病情恶化的速度：在这项研究中，我们首次利用阿尔茨海默病神经影像学倡议（ADNI）数据集分析了有载脂蛋白E4和没有载脂蛋白E4的AD患者这些脑结构的萎缩情况：结果：我们发现，这些脑区的体积在12个月内的减少率与载脂蛋白E4的存在有关。此外，我们还发现，与之前的研究不同，女性和男性患者的神经萎缩并无差异，这表明载脂蛋白E4的存在与AD的性别差异无关：我们的研究结果证实并扩展了之前的研究结果，表明载脂蛋白E4等位基因会逐渐影响受AD影响的大脑区域。

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引用次数: 0

Effects of the Recurrent and Different Doses of Ketamine Exposure on Anxiety-like Behaviors and Locomotor Activity in Juvenile Rats. 反复暴露不同剂量氯胺酮对幼鼠焦虑样行为和运动活动的影响

IF 2.1 4区医学 Q3 CLINICAL NEUROLOGY

Current Alzheimer research

Pub Date : 2023-03-08 DOI: 10.2174/1567205020666230308123718

Ayşe Hande Arpacı, Hasan Çalıskan, Emel Güneş, Berrin Işık

Background: Ketamine is a widely used anesthetic agent. Although the potential adverseeffects of ketamine use in juvenile age are uncertain, certain studies reported that children exposed torecurrent anesthesia could face an increased risk of neurodevelopmental deficits in motor function andbehavioral risks. We aimed to investigate the long-term effects of repeated exposure to various ketaminedoses on anxious behavior and locomotor activity in juvenile rats.

Objective: We aimed to investigate the long-term effects of repeated exposure to various ketaminedoses on anxious behavior and locomotor activity in juvenile rats.

Methods: Thirty-two Wistar Albino juvenile male rats were randomized into 5 mg/kg, 20 mg/kg, and50 mg/kg ketamine (KET) and saline (Group C) Groups and KET was administered for 3 consecutivedays at 3-hour intervals in 3 doses. Ten days after the last KET dose, behavioral parameters were analyzedwith an open field test (OFT), elevated plus maze (EPM), and light-dark box (LDB). Satisticalanalysis was conducted with Kruskall-Wallis test followed by Dunn's Multiple Comparison Test.

Results: Unsupported rearing behavior decreased in 50 mg/kg KET Groups when compared to GroupC. Incorrect transition time, total grooming time, and transfer latency time increased significantly inthe 50 mg/kg KET Group when compared to Group C.

Conclusion: These results suggested that 50 mg/kg KET led to anxiety-like behavior and destroyedmemory and spatial navigation. Ketamine doses were associated with late effects of ketamine on anxiety-like behavior in juvenile rats. Further studies are needed to determine the mechanisms that play arole in the different effects of ketamine doses on anxiety and memory.

背景：氯胺酮是一种广泛使用的麻醉剂：氯胺酮是一种广泛使用的麻醉剂。尽管氯胺酮对幼鼠的潜在不良影响尚不确定，但有研究报告称，反复暴露于氯胺酮麻醉的儿童可能面临运动功能神经发育缺陷和行为风险增加的风险。我们旨在研究反复暴露于各种酮类药物对幼鼠焦虑行为和运动活动的长期影响：我们旨在研究反复暴露于各种酮类药物对幼年大鼠焦虑行为和运动活动的长期影响：将32只Wistar Albino幼年雄性大鼠随机分为5 mg/kg、20 mg/kg、50 mg/kg氯胺酮（KET）组和生理盐水（C组）组，连续3天给予氯胺酮，每次3小时，共3次给药。最后一次服用氯胺酮 10 天后，用开阔地试验 (OFT)、高架迷宫 (EPM) 和光暗箱 (LDB) 分析行为参数。统计分析采用 Kruskall-Wallis 检验和 Dunn's 多重比较检验：结果：与C组相比，50 mg/kg KET组的无支持饲养行为减少。结果：与 C 组相比，50 毫克/千克 KET 组的无支持饲养行为减少；与 C 组相比，50 毫克/千克 KET 组的不正确过渡时间、总梳理时间和转移潜伏时间显著增加：这些结果表明，50 毫克/千克 KET 会导致焦虑样行为，并破坏记忆和空间导航能力。氯胺酮剂量与氯胺酮对幼鼠焦虑样行为的后期影响有关。要确定氯胺酮剂量对焦虑和记忆产生不同影响的机制，还需要进一步的研究。

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