Altered protein expression of membrane transporters in isolated cerebral microvessels and brain cortex of a rat Alzheimer's disease model

There is growing evidence that membrane transporters expressed at the blood-brain barrier (BBB) and brain parenchymal cells play an important role in Alzheimer's disease (AD) development and progression. However, quantitative information about changes in transporter protein expression at neurovascular unit cells in AD is limited. Here, we studied the changes in the absolute protein expression of five ATP-binding cassette (ABC) and thirteen solute carrier (SLC) transporters in the isolated brain microvessels and brain cortical tissue of TgF344-AD rats compared to age-matched wild-type (WT) animals using liquid chromatography tandem mass spectrometry based quantitative targeted absolute proteomic analysis. Moreover, sex-specific alterations in transporter expression in the brain cortical tissue of this model were examined. Protein expressions of Abcg2, Abcc1 and FATP1 (encoded by Slc27a1) in the isolated brain microvessels of TgF344-AD rats were 3.1-, 2.0-, 4.3-fold higher compared to WT controls, respectively (p p Pharmacolog

Mechanistic Study on the Use of the l-Type Amino Acid Transporter 1 for Brain Intracellular Delivery of Ketoprofen via Prodrug: A Novel Approach Supporting the Development of Prodrugs for Intracellular Targets

l-Type amino acid transporter 1 (LAT1), selectively expressed at the blood–brain barrier (BBB) and brain parenchymal cells, mediates brain delivery of drugs and prodrugs such as l-dopa and gabapentin. Although knowledge about BBB transport of LAT1-utilizing prodrugs is available, there is a lack of quantitative information about brain intracellular delivery and influence of prodrugs on the transporter’s physiological state. We studied the LAT1-mediated intrabrain distribution of a recently developed prodrug of the cyclooxygenase inhibitor ketoprofen as well as its impact on transporter protein expression and function (i.e., amino acid exchange) using brain slice method in mice and rats. The intrabrain distribution of the prodrug was 16 times higher than that of ketoprofen. LAT1 involvement in brain cellular barrier uptake of the prodrug was confirmed, reflected by a higher unbound brain intracellular compared to brain extracellular fluid concentration. The prodrug did not alter LAT1 protein expression and amino acid exchange. Integration of derived parameters with previously performed in vivo pharmacokinetic study using the Combinatory Mapping Approach allowed to estimate the brain extra- and intracellular levels of unbound ketoprofen, prodrug, and released parent drug. The overall efficiency of plasma to brain intracellular delivery of prodrug-released ketoprofen was 11 times higher than after ketoprofen dosing. In summary, this study provides quantitative information supporting the use of the LAT1-mediated prodrug approach for enhanced brain delivery of drugs with intracellular targets.Pharmacolog

Recommending exercises in Scratch: an integrated approach for enhancing the learning of computer programming

In this chapter we focused on how to improve the learning of computer programming in college students. From the reported success, we relied on Scratch, a visual programming language for enhancing the informal learning. Despite the progress achieved in the past, we have observe some issues regarding the use of Scratch by college students. First, there is a gap between the employed learning approaches since professors are constrained to classroom activities. Second, certain students feel unmotivated because they are confronted with programming exercises that do not fulfill their individual expectations. So, in order to solve this issue we propose an integrated approach consisting of a simpleWeb Application that includes Scratch as a project editor along with an Recommender System for exercises. The preliminary results demonstrate the positive impact of our proposal

Metabolomic and lipidomic changes triggered by lipopolysaccharide-induced systemic inflammation in transgenic APdE9 mice

Peripheral infections followed by systemic inflammation may contribute to the onset of Alzheimer`s disease (AD) and accelerate the disease progression later in life. Yet, the impact of systemic inflammation on the plasma and brain tissue metabolome and lipidome in AD has not been investigated. In this study, targeted metabolomic and untargeted lipidomic profiling experiments were performed on the plasma, cortices, and hippocampi of wild-type (WT) mice and transgenic APdE9 mice after chronic lipopolysaccharide (LPS) treatment, as well as saline-treated APdE9 mice. The lipidome and the metabolome of these mice were compared to saline-treated WT animals. In the brain tissue of all three models, the lipidome was more influenced than the metabolome. The LPS-treated APdE9 mice had the highest number of changes in brain metabolic pathways with significant alterations in levels of lysine, myo-inositol, spermine, phosphocreatine, acylcarnitines and diacylglycerols, which were not observed in the saline-treated APdE9 mice. In the WT mice, the effect of the LPS administration on metabolome and lipidome was negligible. The study provided exciting information about the biochemical perturbations due to LPS-induced inflammation in the transgenic AD model, which can significantly enhance our understanding of the role of systemic inflammation in AD pathogenesis.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Adsorption of Cd (II) Using Chemically Modified Rice Husk: Characterization, Equilibrium, and Kinetic Studies

Cadmium (Cd) is a highly toxic heavy metal considered carcinogenic to humans. The adsorption behavior of cadmium adsorption using untreated and chemically modified rice husk was investigated. Experimental tests were carried out to evaluate the influence of the variables pH, initial concentration of cadmium, and dosage of adsorbent in the adsorption process. In optimal experimental conditions, the maximum adsorption efficiency was 92.65%. Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM) were used allowing the identification of the main functional groups and morphology of rice husk and treated rice husk, and the results showed an improvement of adsorption characteristics after rice husk treatment with NaOH. The optimum adsorption pH for both types of rice husk was 7. The maximum adsorption capacities of RH and treated RH fitted by the Langmuir model were 5.13 mg/g and 11.06 mg/g, respectively. The pseudosecond order kinetics has the best coefficients of determination for untreated (R2=0.992) and treated (R2=0.999) rice husk. The adsorption process was found to be endothermic in nature with enthalpy of 14.08 kJ/mol and entropy of 170.98 J/mol.K. The calculated activation energy was 24 kJ/mol. The results showed the potential of rice husk as a low-cost, easily managed, and efficient biosorbent for Cd removal from waters