High-Fat Diet Leads to Reduced Protein O-GlcNAcylation and Mitochondrial Defects Promoting the Development of Alzheimer’s Disease Signatures

The disturbance of protein O-GlcNAcylation is emerging as a possible link between altered brain metabolism and the progression of neurodegeneration. As observed in brains with Alzheimer’s disease (AD), flaws of the cerebral glucose uptake translate into reduced protein O-GlcNAcylation, which promote the formation of pathological hallmarks. A high-fat diet (HFD) is known to foster metabolic dysregulation and insulin resistance in the brain and such effects have been associated with the reduction of cognitive performances. Remarkably, a significant role in HFD-related cognitive decline might be played by aberrant protein O-GlcNAcylation by triggering the development of AD signature and mitochondrial impairment. Our data support the impairment of total protein O-GlcNAcylation profile both in the brain of mice subjected to a 6-week high-fat-diet (HFD) and in our in vitro transposition on SH-SY5Y cells. The reduction of protein O-GlcNAcylation was associated with the development of insulin resistance, induced by overfeeding (i.e., defective insulin signaling and reduced mitochondrial activity), which promoted the dysregulation of the hexosamine biosynthetic pathway (HBP) flux, through the AMPK-driven reduction of GFAT1 activation. Further, we observed that a HFD induced the selective impairment of O-GlcNAcylated-tau and of O-GlcNAcylated-Complex I subunit NDUFB8, thus resulting in tau toxicity and reduced respiratory chain functionality respectively, highlighting the involvement of this posttranslational modification in the neurodegenerative process.     

Insoluble Vascular Amyloid Deposits Trigger Disruption of the Neurovascular Unit in Alzheimer’s Disease Brains

Alzheimer’s disease (AD) is a neurodegenerative disease, characterized histopathologically by intra-neuronal tau-related lesions and by the accumulation of amyloid β-peptide (Aβ) in the brain parenchyma and around cerebral blood vessels. According to the vascular hypothesis of AD, an alteration in the neurovascular unit (NVU) could lead to Aβ vascular accumulation and promote neuronal dysfunction, accelerating neurodegeneration and dementia. To date, the effects of insoluble vascular Aβ deposits on the NVU and the blood–brain barrier (BBB) are unknown. In this study, we analyze different Aβ species and their association with the cells that make up the NVU. We evaluated post-mortem AD brain tissue. Multiple immunofluorescence assays were performed against different species of Aβ and the main elements that constitute the NVU. Our results showed that there are insoluble vascular deposits of both full-length and truncated Aβ species. Besides, insoluble aggregates are associated with a decrease in the phenotype of the cellular components that constitute the NVU and with BBB disruption. This approach could help identify new therapeutic targets against key molecules and receptors in the NVU that can prevent the accumulation of vascular fibrillar Aβ in AD.     

Molecular Mechanisms Underlying the Beneficial Effects of Exercise on Brain Function and Neurological Disorders

As life expectancy has increased, particularly in developed countries, due to medical advances and increased prosperity, age-related neurological diseases and mental health disorders have become more prevalent health issues, reducing the well-being and quality of life of sufferers and their families. In recent decades, due to reduced work-related levels of physical activity, and key research insights, prescribing adequate exercise has become an innovative strategy to prevent or delay the onset of these pathologies and has been demonstrated to have therapeutic benefits when used as a sole or combination treatment. Recent evidence suggests that the beneficial effects of exercise on the brain are related to several underlying mechanisms related to muscle–brain, liver–brain and gut–brain crosstalk. Therefore, this review aims to summarize the most relevant current knowledge of the impact of exercise on mood disorders and neurodegenerative diseases, and to highlight the established and potential underlying mechanisms involved in exercise–brain communication and their benefits for physiology and brain function.     

Revisiting Platinum-Based Anticancer Drugs to Overcome Gliomas

Although there are many patients with brain tumors worldwide, there are numerous difficulties in overcoming brain tumors. Among brain tumors, glioblastoma, with a 5-year survival rate of 5.1%, is the most malignant. In addition to surgical operations, chemotherapy and radiotherapy are generally performed, but the patients have very limited options. Temozolomide is the most commonly prescribed drug for patients with glioblastoma. However, it is difficult to completely remove the tumor with this drug alone. Therefore, it is necessary to discuss the potential of anticancer drugs, other than temozolomide, against glioblastomas. Since the discovery of cisplatin, platinum-based drugs have become one of the leading chemotherapeutic drugs. Although many studies have reported the efficacy of platinum-based anticancer drugs against various carcinomas, studies on their effectiveness against brain tumors are insufficient. In this review, we elucidated the anticancer effects and advantages of platinum-based drugs used in brain tumors. In addition, the cases and limitations of the clinical application of platinum-based drugs are summarized. As a solution to overcome these obstacles, we emphasized the potential of a novel approach to increase the effectiveness of platinum-based drugs.     

Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases

Neurodegenerative diseases (NDs) including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease are incurable and affect millions of people worldwide. The development of treatments for this unmet clinical need is a major global research challenge. Computer-aided drug design (CADD) methods minimize the huge number of ligands that could be screened in biological assays, reducing the cost, time, and effort required to develop new drugs. In this review, we provide an introduction to CADD and examine the progress in applying CADD and other molecular docking studies to NDs. We provide an updated overview of potential therapeutic targets for various NDs and discuss some of the advantages and disadvantages of these tools.     

PPV Nanotube Sensor Arrays for Explosives Identification by Excitation Wavelength Regulation

The development of sensitive materials for standard and improvised explosives is greatly significant to homeland security. In this paper, the phosphotungstate (NaPT) doped polyphenylene vinylene (PPV) nanotube arrays (NTAs), with excellent optical response, chemical stability, and larger specific surface area, are successfully fabricated by means of the “precursor film” infiltration method. The efficient charge carriers' separation of PPV NTAs can be achieved by doping NaPT to realize the photoelectric detection of explosive vapors. In addition, the identification of six explosives, including ammonium nitrate (AN), dinitrotoluence (DNT), picric acid (PA), p-nitrotoluene (PNT), triacetone triperoxide (TATP), and trinitrotoluene (TNT), can also be realized through the fingerprint atlas. Moreover, the adsorption energy and excited oscillator intensity has also been employed to explain the interaction between NaPT doped PPV nanotube arrays and various explosive molecules. Obviously, the NaPT doped PPV developed has the potential to be used as an explosive sensor.     

数据挖掘预测模型在脑损伤患者认知功能康复中的应用

为了更好地预测后天性脑损伤ABI(Acquired Brain Injury)患者认知功能康复的影响因素,提出基于决策树(DT)、多层感知器(MLP)和广义回归神经网络(GRNN)的三种预测模型。借助于10折交叉验证测试算法,通过专一性、灵敏度和精度分析以及混淆矩阵分析对模型的性能进行测试,从而获得新的知识以评估和改善认知功能康复过程中的有效性。实验结果表明,基于DT的模型的模拟结果明显比其他模型更为优越,预测平均精度可高达90.38%。     

基于C-V模型和MRF的脑部MRI分割

为准确分割脑部磁共振图像(MRI)的灰质、白质和背景,提出一种基于C-V模型和马尔可夫随机场的全自动分割方法。采用C-V模型与形态学相结合的方法对脑MRI进行预处理,去除多余脑组织,获得待分割图像。引入灰度场局部熵的思想对惩罚因子进行估计,利用马尔可夫随机场模型建模实现脑灰白质的分割,并运用形态学方法获得最终分割结果。对96幅IBSR图像和46幅临床图像进行实验,结果表明,该方法能够实现脑部MRI灰白质的全自动分割,且具有较好的分割精度和较快的处理速度。     

培哚普利与缬沙坦对高胆固醇兔脑组织AngⅡ的影响及其抗氧化应激作用

目的探讨高胆固醇兔脑组织RAAS与氧化应激的关系及培哚普利、缬沙坦的干预效果;方法:32只健康新西兰白兔随机分为4组:正常组,高脂组,培哚普利组,缬沙坦组。喂饲8周后,测定血清总胆固醇(Total cholesterol,TC)及低密度脂蛋白(Low den-sity lipoprotein,LDL)浓度。取脑组织测血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ),血红素氧合酶(hemo oxygenase-1,HO-1)的表达及超氧化物岐化酶(SOD)活力,丙二醛(MDA)含量;结果:与正常组相比,高脂组AngⅡ,HO-1表达明显增强,SOD活力下降,MDA升高,培哚普利可降低AngⅡ,而缬沙坦不能,二者均可使HO-1表达上调,SOD活力升高,MDA降低;结论:1)高胆固醇血症时脑组织处于氧化应激状态,肾素血管紧张素醛固酮系统(Rennin-angiotensin-aldosterone system RAAS)激活;2)培哚普利和缬沙坦对组织具有抗氧化应激的保护作用。     

癫痫脑电的递归确定性分析

利用排序递归图的分析方法对癫痫脑电进行了确定性(DET)的分析,得出癫痫头皮脑电(EEG)的DET高于健康EEG。DET特征的差异性在局部导联上更明显,局部导联的DET特征可以作为癫痫疾病的自动诊断特征。通过分析发作阶段和发作间隙皮层脑电(ECoG)的DET,得出整个频带的DET差别不大,而在beta频带,发作阶段的确定性明显高于发作间隙的DET。Beta频带的DET特征可以作为癫痫发作的预测特征。研究结果为癫痫疾病的自动诊断和癫痫发作预测提供了理论依据。