1,720,958 research outputs found
Effects of Long-Term Environmental Enrichment on Anxiety, Memory, Hippocampal Plasticity and Overall Brain Gene Expression in C57BL6 Mice
No full textThere is ample evidence that physical activity exerts positive effects on a variety of brain functions by facilitating neuroprotective processes and influencing neuroplasticity. Accordingly, numerous studies have shown that continuous exercise can successfully diminish or prevent the pathology of neurodegenerative diseases such as Alzheimer’s disease in transgenic mouse models. However, the long-term effect of physical activity on brain health of aging WT mice has not been studied in detail yet. Here, we show that prolonged physical and cognitive stimulation, mediated by an enriched environment (EE) paradigm for a duration of eleven months, leads to reduced anxiety and improved spatial reference memory in C57BL6 wildtype (WT) mice. While the number of CA1 pyramidal neurons remained unchanged between standard housed (SH) and EE mice, the number of dentate gyrus (DG) neurons, as well as the CA1 and DG volume were significantly increased in EE mice. A whole-brain deep sequencing transcriptome analysis, carried out to better understand the molecular mechanisms underlying the observed effects, revealed an up-regulation of a variety of genes upon EE, mainly associated with synaptic plasticity and transcription regulation. The present findings corroborate the impact of continuous physical activity as a potential prospective route in the prevention of age-related cognitive decline and neurodegenerative disorders
Neprilysin Deficiency Alters the Neuropathological and Behavioral Phenotype in the 5XFAD Mouse Model of Alzheimer's Disease
No full textThe deposition of amyloid-beta (A beta) is one of the major neuropathological hallmarks of Alzheimer's disease (AD). In the case of sporadic AD, an imbalance in A beta in production and clearance seems to be the reason for an enhanced A beta accumulation. Besides a systematic clearance through the blood-brain barrier, A beta is cleared from the brain by A beta-degrading enzymes. The metalloprotease neprilysin (NEP) is an important A beta-degrading enzyme as shown by numerous in vitro, in vivo and reverse genetics studies. 5XFAD mice represent an early-onset AD mouse model which develops plaque pathology starting with 2 months of age in addition to robust behavioral deficits at later time points. By crossing 5XFAD mice with homozygous NEP-knock-out mice (NEP-/-), we show that hemizygous NEP deficiency aggravates the behavioral and neuropathological phenotype of 5XFAD mice. We found that 5XFAD mice per se showed strongly decreased NEP expression levels compared to wildtype mice, which was aggravated by NEP reduction. 5XFAD/NEP+/- mice demonstrated impairment in spatial working memory and increased astrocytosis in all studied brain areas, in addition to an overall increased level of soluble A beta(42) as well as region-specific increases in extracellular A beta deposition. Surprisingly, in young mice, a more abundant cortical A beta plaque pathology was observed in 5XFAD compared to 5XFAD/NEP+/- mice. Additionally, young 5XFAD/NEP+/- as well as hemiand homozygous NEP knockout mice showed elevated levels of endothelin-converting enzyme 1 (ECE1), suggesting a mutual regulation of ECE1 and NEP at young ages. The present data indicate that NEP mainly degrades soluble A beta peptides, which confirms previous observations. Increased ECE1 levels correlated well with the strongly reduced extracellular plaque load in young 5XFAD/NEP+/- mice and might suggest a reciprocal effect between ECE and NEP activities in A beta degradation.Alzheimer Forschung Initiative e.V.; Gerhard-Hunsmann-Stiftun
Axonal degeneration in an Alzheimer mouse model is PS1 gene dose dependent and linked to intraneuronal Aß accumulation
Full text linkAbnormalities and impairments in axonal transport are suggested to strongly contribute to the pathological alterations underlying AD. The exact mechanisms leading to axonopathy are currently unclear, but it was recently suggested that APP expression itself triggers axonal degeneration. We used APP transgenic mice and crossed them on a hemi- or homozygous PS1 knock-in background (APP/PS1KI). Depending on the mutant PS1 dosage, we demonstrate a clear aggravation in both plaque-associated and plaque-distant axonal degeneration, despite of an unchanged APP expression level. Amyloid-ß (Aβ) peptides were found to accumulate in axonal swellings as well as in axons and apical dendrites proximate to neurons accumulating intraneuronal Aβ in their cell bodies. This suggests that Aβ can be transported within neurites thereby contributing to axonal deficits. In addition, diffuse extracellular Aβ deposits were observed in the close vicinity of axonal spheroids accumulating intracellular Aβ, which might be indicative of a local Aβ release from sites of axonal damage
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Gene Expression Profiling in the APP/PS1KI Mouse Model of Familial Alzheimer’s Disease
No full textAlzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by early intraneuronal amyloid-beta (A beta) accumulation, extracellular deposition of A beta peptides, and intracellular hyperphosphorylated tau aggregates. These lesions cause dendritic and synaptic alterations and induce an inflammatory response in the diseased brain. Although the neuropathological characteristics of AD have been known for decades, the molecular mechanisms causing the disease are still under investigation. Studying gene expression changes in postmortem AD brain tissue can yield new insights into the molecular disease mechanisms. To that end, one can employ transgenic AD mouse models and the next-generation sequencing technology. In this study, a whole-brain transcriptome analysis was carried out using the well-characterized APP/PS1KI mouse model for AD. These mice display a robust phenotype reflected byworking memory deficits at 6 months of age, a significant neuron loss in a variety of brain areas including the CA1 region of the hippocampus and a severe amyloid pathology. Based on deep sequencing, differentially expressed genes (DEGs) between 6-month-old WT or PS1KI and APP/PS1KI were identified and verified by qRT-PCR. Compared to WT mice, 250 DEGs were found in APP/PS1KI mice, while 186 DEGs could be found compared to PS1KI control mice. Most of the DEGs were upregulated in APP/PS1KI mice and belong to either inflammation-associated pathways or lysosomal activation, which is likely due to the robust intraneuronal accumulation of A beta in this mouse model. Our comprehensive brain transcriptome study further highlights APP/PS1KI mice as a valuable model for AD, covering molecular inflammatory and immune responses
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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