Effect of obesity on blood-brain barrier integrity in ischemic brain using mouse model

One of the consequences of obesity is the brain ischemia which is leading to the loss of blood-brain barrier to its integrity and subsequently to the accumulation of Beta-amyloid peptide which leads to the early onset of the Alzheimer's disease. The interest of this study was investigating the various factors which may impact the degradation or the clearance of the peptide. To achieve this goal, in-vivo and in-vitro studies were conducted concerning the enzymatic activity that involved in the degradation process of the peptide and the impact of natural compounds that influencing the accumulation and/or clearance of the peptide, respectively. Furthermore, a study of the hypothesized role of the peptide as an anti-microbial agent was considered too. Impact of cholesterol on the Insulin-degrading enzyme (IDE) was considered. On the cell surface, many enzymes could be implicated in the degrading process including IDE. However, it was found that IDE is the predominant enzyme which degrades the peptide between cells. The aforementioned investigation was performed by employing several cell lines and experiments and using fluorescence and absorbance plate reader, WB, and qRT-PCR techniques. While, investigating the impact of chemical compounds was performed by using circular dichroism spectrometry (CD). AlamarBlue assay was employed in investigating the role of the peptide as AMP.Die Ischämie des Gehirns und der daraus entstehende Verlust der Integrität der Blut-Hirn-Schranke ist eine Folge von Adipositas. Daraufhin kommt es zur Akkumulation vom Beta-Amyloid Peptiden und daraus folgend zu einer frühen Manifestation von Alzheimer Demenz. Das Ziel dieser Studie war es, die verschiedenen Einflussfaktoren der Degradation und Clearance des Beta-Amyloids zu untersuchen. Zu diesem Zweck wurden in-vivo und in-vitro Modelle benutzt, um die Enzymaktivität in der Peptid-Degradation sowie den Einfluss von natürlichen Verbindungen auf die Akkumulation bzw. Clearance zu beobachten. Die vermutete Rolle des Beta-Amyloids als antimikrobielles Peptid wurde außerdem untersucht. Viele Enzyme an der Zelloberfläche, unter anderem auch das Insulin-degrading Enzyme (IDE), können an der Degradation des Beta-Amyloids beteiligt sein. Jedoch konnte IDE als das vorherrschende Enzym der Degradation zwischen den Zellen ausgemacht werden. Auch die Cholesterol-Wirkung auf das Insulin-degrading Enzyme (IDE) wurde angesehen. Die beschriebenen Untersuchungen konnten mittels verschiedener Zelllinien, Fluoreszenz- und Extinktionsmessungen, Western Blot und qRT-PCR durchgeführt werden. Dagegen wurde der Einfluss chemischer Verbindungen mit der Circulardichroismus-Spektroskopie untersucht. Die Rolle des Beta-Amyloids als antimikrobielles Peptid konnte mittels AlamarBlue-Assay untersucht werden

Consequential Effects of Defence Expenditure on Economic Growth of Saudi Arabia: 1970-2012

This study investigates the causality relationship between defence expenditures and Non Oil economic growth in Saudi Arabia over the period 1970-2012. Using Unit root tests, Johansen’s co-integration test and Granger Causality test. In this paper we found the existence of bi-directional causality relationship running from Non Oil-GDP to defence expenditure. The results show that, in Saudi Arabia, the model of defence expenditure is found to hold for Non Oil-GDP

Saudi Financial Structure and Economic Growth: A Macroeconometric Approach

This paper investigates the nexus between financial sector development and economic growth in the Saudi economy over the period 1970-2012 by using four alternative proxies for financial development and several techniques including unit root tests, the co-integration test, the Granger Causality Test, and the Vector Error Correction Model (VECM). We used time series econometrics techniques to examine the causal relationship between financial sector development and economic growth in the Saudi economy. The results obtained from the analyses show that there is a positive relationship between financial sector development and economic growth in Saudi Arabia. The development of the financial system will thus have a positive impact on the growth of the Saudi economy

Consequential Effects of Defence Expenditure on Economic Growth of Saudi Arabia: 1970-2012

This study investigates the causality relationship between defence expenditures and Non Oil economic growth in Saudi Arabia over the period 1970-2012. Using Unit root tests, Johansen’s co-integration test and Granger Causality test. In this paper we found the existence of bi-directional causality relationship running from Non Oil-GDP to defence expenditure. The results show that, in Saudi Arabia, the model of defence expenditure is found to hold for Non Oil-GDP

Tocotrienol Affects Oxidative Stress, Cholesterol Homeostasis and the Amyloidogenic Pathway in Neuroblastoma Cells: Consequences for Alzheimer’s Disease

One of the characteristics of Alzheimer´s disease (AD) is an increased amyloid load and an enhanced level of reactive oxidative species (ROS). Vitamin E has known beneficial neuroprotective effects, and previously, some studies suggested that vitamin E is associated with a reduced risk of AD due to its antioxidative properties. However, epidemiological studies and nutritional approaches of vitamin E treatment are controversial. Here, we investigate the effect of α-tocotrienol, which belongs to the group of vitamin E, on AD-relevant processes in neuronal cell lines. In line with the literature, α-tocotrienol reduced the ROS level in SH-SY5Y cells. In the presence of tocotrienols, cholesterol and cholesterol esters, which have been shown to be risk factors in AD, were decreased. Besides the unambiguous positive effects of tocotrienol, amyloid-β (Aβ) levels were increased accompanied by an increase in the activity of enzymes responsible for Aβ production. Proteins and gene expression of the secretases and their components remained unchanged, whereas tocotrienol accelerates enzyme activity in cell-free assays. Besides enhanced Aβ production, tocotrienols inhibited Aβ degradation in neuro 2a (N2a)-cells. Our results might help to understand the controversial findings of vitamin E studies and demonstrate that besides the known positive neuroprotective properties, tocotrienols also have negative characteristics with respect to AD

Tocotrienol Affects Oxidative Stress, Cholesterol Homeostasis and the Amyloidogenic Pathway in Neuroblastoma Cells: Consequences for Alzheimer’s Disease

One of the characteristics of Alzheimer´s disease (AD) is an increased amyloid load and an enhanced level of reactive oxidative species (ROS). Vitamin E has known beneficial neuroprotective effects, and previously, some studies suggested that vitamin E is associated with a reduced risk of AD due to its antioxidative properties. However, epidemiological studies and nutritional approaches of vitamin E treatment are controversial. Here, we investigate the effect of α-tocotrienol, which belongs to the group of vitamin E, on AD-relevant processes in neuronal cell lines. In line with the literature, α-tocotrienol reduced the ROS level in SH-SY5Y cells. In the presence of tocotrienols, cholesterol and cholesterol esters, which have been shown to be risk factors in AD, were decreased. Besides the unambiguous positive effects of tocotrienol, amyloid-β (Aβ) levels were increased accompanied by an increase in the activity of enzymes responsible for Aβ production. Proteins and gene expression of the secretases and their components remained unchanged, whereas tocotrienol accelerates enzyme activity in cell-free assays. Besides enhanced Aβ production, tocotrienols inhibited Aβ degradation in neuro 2a (N2a)-cells. Our results might help to understand the controversial findings of vitamin E studies and demonstrate that besides the known positive neuroprotective properties, tocotrienols also have negative characteristics with respect to AD