Memory deficits in APP23/Abca1+/− mice correlate with the level of Aβ oligomers

ABCA1, a member of the ATP-binding cassette family of transporters, lipidates ApoE (apolipoprotein A) and is essential for the generation of HDL (high-density lipoprotein)-like particles in the CNS (central nervous system). Lack of Abca1 increases amyloid deposition in several AD (Alzheimer's disease) mouse models. We hypothesized that deletion of only one copy of Abca1 in APP23 (where APP is amyloid precursor protein) AD model mice will aggravate memory deficits in these mice. Using the Morris Water Maze, we demonstrate that 2-year-old Abca1 heterozygous APP23 mice (referred to as APP23/het) have impaired learning during acquisition, and impaired memory retention during the probe trial when compared with age-matched wild-type mice (referred to as APP23/wt). As in our previous studies, the levels of ApoE in APP23/het mice were decreased, but the differences in the levels of Aβ and thioflavin-S-positive plaques between both groups were insignificant. Importantly, dot blot analysis demonstrated that APP23/het mice have a significantly higher level of soluble A11-positive Aβ (amyloid β protein) oligomers compared with APP23/wt which correlated negatively with cognitive performance. To confirm this finding, we performed immunohistochemistry with the A11 antibody, which revealed a significant increase of A11-positive oligomer structures in the CA1 region of hippocampi of APP23/het. This characteristic region-specific pattern of A11 staining was age-dependent and was missing in younger APP23 mice lacking Abca1. In contrast, the levels of Aβ*56, as well as other low-molecular-mass Aβ oligomers, were unchanged among the groups. Overall, the results of the present study demonstrate that in aged APP23 mice memory deficits depend on Abca1 and are likely to be mediated by the amount of Aβ oligomers deposited in the hippocampus

Personality traits as determinants of political behavior: Ukrainian electoral and voting tendencies

Now there is a sharp increase of interest in politics, especially among young people. Meanwhile, the psychological mechanisms of the person’s political behavior (its manifesting and regulating), as well as interaction of his cognitive, emotional, motivation and value factors with the political system remain insufficiently studied. The aim of this research is to study the influence of personality traits on political behavior in order to find out the connection between person’s individual-psychological characteristics and the degree of his participation in political life within the territory of Ukraine. The Five-Factor NEO-PI-R (NEO Personality Inventory-Revised) model was used for analyzing the respondents’ tendency to politically significant behavior. The survey was conducted in 2017 in Ukraine (n=1247, age: 15-50 years). A positive correlation of the political participation indicators with the personal indicator Conscientiousness and the negative correlation with the Agreeableness parameter were revealed. We have established that emotionally balanced respondents more often show a desire to run for office and rarely participate in voting. High results for Agreeableness and Neuroticism determine the low level of political ambitions. These findings constitute a new step forward in understanding how personality traits form responses in the people’s political engagement while demonstrating the Ukrainian political tendencies

DETERMINATION OF CHIP LENGTH COMPRESSION RATIO AT ONE-EDGE DRILLS

Increasing the volume of chips, taken per unit of time under conditions of high speeds and temperatures of the cutting, makes the problem of reliably shredding the chips and their effective removal from the cutting zone, particularly topical. The present scientific development examines the determination of the chip length compression ratio according to the proposed methodology. Presented are the results of the theoretical and experimental studies made according to the methodology

DETERMINATION OF PLASTIC DEFORMATION COEFFICIENT FOR ONE-EDGE DRILLS

The plastic deformation coefficient, also called the relative plastic deformation, is related to the angle of shifting of the chip and the rake angle of the tool. Studying the nature of chip shifting and deforming layer material relative to the face and major flank of the tool is of great importance for determining both the workability of the materials and the correct choice of cutting tool characteristics. This article proposes a methodology based on mathematical dependencies for determining the coefficient of plastic deformation. Theoretical results are presented based on the proposed methodology, as well as results of experimental studies

Expression profiling in APP23 mouse brain: inhibition of Aβ amyloidosis and inflammation in response to LXR agonist treatment

BACKGROUND:Recent studies demonstrate that in addition to its modulatory effect on APP processing, in vivo application of Liver X Receptor agonist T0901317 (T0) to APP transgenic and non-transgenic mice decreases the level of Aß42. Moreover, in young Tg2576 mice T0 completely reversed contextual memory deficits. Compared to other tissues, the regulatory functions of LXRs in brain remain largely unexplored and our knowledge so far is limited to the cholesterol transporters and apoE. In this study we applied T0 to APP23 mice for various times and examined gene and protein expression. We also performed a series of experiments with primary brain cells derived from wild type and LXR knockout mice subjected to various LXR agonist treatments and inflammatory stimuli.RESULTS:We demonstrate an upregulation of genes related to lipid metabolism/transport, metabolism of xenobiotics and detoxification. Downregulated genes are involved in immune response and inflammation, cell death and apoptosis. Additional treatment experiments demonstrated an increase of soluble apolipoproteins E and A-I and a decrease of insoluble Aß. In primary LXRwt but not in LXRa-/-ß-/- microglia and astrocytes LXR agonists suppressed the inflammatory response induced by LPS or fibrillar Aß.CONCLUSION:The results show that LXR agonists could alleviate AD pathology by acting on amyloid deposition and brain inflammation. An increased understanding of the LXR controlled regulation of Aß aggregation and clearance systems will lead to the development of more specific and powerful agonists targeting LXR for the treatment of AD

E47 is required for V(D)J recombinase activity in common lymphoid progenitors

Common lymphoid progenitors (CLPs) are the first bone marrow precursors in which V(D)J recombinase activity is up-regulated. Here, we show that loss of the transcription factor E47 produces a reduced CLP population that lacks V(D)J recombinase activity and D-JH rearrangements in vivo. Apart from a profound arrest before the pro–B cell stage, other downstream lymphoid progeny of CLPs are still intact in these mice albeit at reduced numbers. In contrast to the inhibition of recombinase activity in early B lineage precursors in E47-deficient animals, loss of either E47 or its cis-acting target Erag (enhancer of rag transcription) has little effect on recombinase activity in thymic T lineage precursors. Taken together, this work defines a role for E47 in regulating lineage progression at the CLP stage in vivo and describes the first transcription factor required for lineage-specific recombinase activity

A NEW APPROACH TO INTERPRETATION OF SALIVARY ALFA AMYLASE ACTIVITY CHANGES AS A STRESS INDICATOR

Contemporary sport induces a serious physical and mental stress in athletes. This could result in lowering of their sports performance. Thus, the evaluation of stress in athletes is an important milestone in their preparation. Establishing levels of stress would allow targeted work by coaches and sports specialists to increase the resistance of competitors to stress. In this regard, the use of non-invasive methods for stress testing is essential. Recently, the use of saliva as a biological research material becomes of increasing interest. The aim of this study was to establish the potential of alpha amylase activity, protein and potassium concentrations in saliva to reflect adequately the degree of stress in athletes. Eleven boxers, participants in the National Championship, took part in the study. Saliva was collected by salivetes three times: 1) one week before the competition, 2) before the draw of lot, and 3) before the first bout. The salivary alpha amylase activity (sAA), protein and potassium concentrations were detected with commercially available kits. The sAA, protein and K+ concentrations rose significantly in stress conditions. The individual values of sAA showed large differences that could be explained by the poly-allelic expression of sAA whose activity depends on the number of alleles (2 to 14) with each individual. All tested indices could serve as indicators for evaluation of stress level in athletes as a high correlation between the protein and K+ and sAA values was found. In order to evaluate the changes in sAA and to compare the individual results be-tween athletes we suggested the sAA to be presented in relative units. The activities, measured in calm conditions long time before a competition could be assumed as a baseline and the coefficient of increase in sAA in a stressful condition could be accepted as a “stress coefficient”

ABCA1 Deficiency Affects Basal Cognitive Deficits and Dendritic Density in Mice

Producción CientíficaATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux to lipid-free apolipoproteins and regulates the generation of high density lipoproteins. Previously, we have shown that lack of Abca1 significantly increases amyloid deposition and cognitive deficits in Alzheimer’s disease model mice expressing human amyloid-β protein precursor (APP). The goal of this study was to determine if ABCA1 plays a role in memory deficits caused by amyloid-β (Aβ) oligomers and examine neurite architecture of pyramidal hippocampal neurons. Our results confirm previous findings that Abca1 deficiency significantly impairs spatial memory acquisition and retention in the Morris water maze and long-term memory in novel object recognition of APP transgenic mice at a stage of early amyloid pathology. Neither test demonstrated a significant difference between Abca1ko and wild-type (WT) mice. We also examined the effect of intra-hippocampal infused Aβ oligomers on cognitive performance of Abca1ko mice, compared to control infusion of scrambled Aβ peptide. Age-matched WT mice undergoing the same infusions were also used as controls. In this model system, we found a statistically significant difference between WT and Abca1ko mice infused with scrambled Aβ, suggesting that Abca1ko mice are vulnerable to the effect of mild stresses. Moreover, examination of neurite architecture in the hippocampi revealed a significant decrease in neurite length, number of neurite segments, and branches in Abca1ko mice when compared to WT mice. We conclude that mice lacking ABCA1 have basal cognitive deficits that prevent them from coping with additional stressors, which is in part due to impairment of neurite morphology in the hippocampus

Проблемы психологического здоровья и предоставления психологических услуг населению

Статья посвящена теоретико-прикладному анализу проблем психологического здоровья и предоставления психологических услуг населению. Приводится рассмотрение понятий психическое и психологическое здоровье, факторов и современного состояния психологического здоровья украинцев. Обосновывается необходимость распространения психологической практики и создания и развития эффективной системы предоставления психологических услуг населению.The article is devoted to theoretical and applied analysis of problems of psychological health and psychological service delivery to the public. There is given discussion of concepts mental and psychological health factors and the current state of mental health of Ukrainian people. The necessity of psychological practice spreading and creation and development of efficient provision of psychological services are grounded

Opposing effects ofApoe/Apoa1double deletion on amyloid-β pathology and cognitive performance in APP mice

Producción CientíficaATP binding cassette transporter A1 (encoded by ABCA1) regulates cholesterol efflux from cells to apolipoproteins A-I and E (ApoA-I and APOE; encoded by APOA1 and APOE, respectively) and the generation of high density lipoproteins. In Abca1 knockout mice (Abca1(ko)), high density lipoproteins and ApoA-I are virtually lacking, and total APOE and APOE-containing lipoproteins in brain substantially decreased. As the ε4 allele of APOE is the major genetic risk factor for late-onset Alzheimer's disease, ABCA1 role as a modifier of APOE lipidation is of significance for this disease. Reportedly, Abca1 deficiency in mice expressing human APP accelerates amyloid deposition and behaviour deficits. We used APP/PS1dE9 mice crossed to Apoe and Apoa1 knockout mice to generate Apoe/Apoa1 double-knockout mice. We hypothesized that Apoe/Apoa1 double-knockout mice would mimic the phenotype of APP/Abca1(ko) mice in regards to amyloid plaques and cognitive deficits. Amyloid pathology, peripheral lipoprotein metabolism, cognitive deficits and dendritic morphology of Apoe/Apoa1 double-knockout mice were compared to APP/Abca1(ko), APP/PS1dE9, and single Apoa1 and Apoe knockouts. Contrary to our prediction, the results demonstrate that double deletion of Apoe and Apoa1 ameliorated the amyloid pathology, including amyloid plaques and soluble amyloid. In double knockout mice we show that (125)I-amyloid-β microinjected into the central nervous system cleared at a rate twice faster compared to Abca1 knockout mice. We tested the effect of Apoe, Apoa1 or Abca1 deficiency on spreading of exogenous amyloid-β seeds injected into the brain of young pre-depositing APP mice. The results show that lack of Abca1 augments dissemination of exogenous amyloid significantly more than the lack of Apoe. In the periphery, Apoe/Apoa1 double-knockout mice exhibited substantial atherosclerosis and very high levels of low density lipoproteins compared to APP/PS1dE9 and APP/Abca1(ko). Plasma level of amyloid-β42 measured at several time points for each mouse was significantly higher in Apoe/Apoa1 double-knockout then in APP/Abca1(ko) mice. This result demonstrates that mice with the lowest level of plasma lipoproteins, APP/Abca1(ko), have the lowest level of peripheral amyloid-β. Unexpectedly, and independent of amyloid pathology, the deletion of both apolipoproteins worsened behaviour deficits of double knockout mice and their performance was undistinguishable from those of Abca1 knockout mice. Finally we observed that the dendritic complexity in the CA1 region of hippocampus but not in CA2 is significantly impaired by Apoe/Apoa1 double deletion as well as by lack of ABCA1. In conclusion: (i) plasma lipoproteins may affect amyloid-β clearance from the brain by the 'peripheral sink' mechanism; and (ii) deficiency of brain APOE-containing lipoproteins is of significance for dendritic complexity and cognition