1,720,978 research outputs found
A COMBINED STUDY OF NEUROPHARMACOLOGICAL EFFECTS: FROM BEHAVIORAL TESTS TO CYTOFLUORIMETRIC ANALYSIS
No full textSeveral neurodegenerative diseases cause locomotor disabilities and mood disorders. Therefore, it could be relevant to define behavioral schemes to either predict the diagnosis or recognize mood alterations as a comorbidity in neurodegenerative processes. So, this PhD project aims to design a combined behavioral analysis protocol to assess anxiety-like and stress disorders. To carry out this, a series of behavioral analysis of mice under various condition, including age, sex, and drug treatments were conducted. Furthermore, in this context this approach was applied to some disease models (EAE and G93A mice) in which we have tried to find: early onset, features not previously evaluated and clustering of animals. During this period, the basics of open-source animal monitoring software were perfected through computer-based analysis. Thanks to this knowledge and integration with the previous software, we were able to describe new behavioral aspects. The behavioral analysis was further enriched by the application of multivariate statistical approaches. In addition, neurodegenerative diseases may be related to synaptic dysfunction and toxicity. Researchers can identify the causes of synaptic derangements such as neurotoxic compounds, oxidative stress, and inflammation. There is a growing need for innovative techniques and methods to find the cause of synaptic dysfunction and toxicity as early as possible and prevent the consequences. The second goal of the project was to improve a flow cytometric method to study synaptic toxicity on isolated nerve endings. Flow cytometry is widely used to check neuronal death, detect neurotoxic compounds, and analyze synaptic proteins and biomarkers of neurodegenerative diseases. Starting from a consolidated protocol, we decided to use the observations of a recent critical analysis (artefacts) and implement the monitored signals. This method has enabled the analysis of synaptic toxicity in various contexts, including the pruning phenomenon.
The combination of these two approaches in vivo and in vitro could allow us to intervene earlier with pharmacological treatment and highlight common features of neurodegenerative diseases
The Anti-Aggregative Peptide KLVFF Mimics Aβ1-40 in the Modulation of Nicotinic Receptors: Implications for Peptide-Based Therapy
No full textIn recent years, the inhibition of beta-amyloid (Aβ) aggregation has emerged as a potential strategy for Alzheimer’s disease. KLVFF, a small peptide corresponding to the aminoacidic sequence 16-20 of Aβ, reduces Aβ fibrillation dose dependently. Therefore, the toxic and functional characterization of its brain activity is fundamental for clarifying its potential therapeutic role. Accordingly, we studied the modulatory role of KLVFF on the cholinergic receptors regulating dopamine and noradrenaline release in rat synaptosomes. Nicotinic receptors on dopaminergic nerve terminals in the nucleus acccumbens are inhibited by KLVFF, which closely resembles full-length Aβ1-40. Moreover, KLVFF entrapped in synaptosomes does not modify the nicotinic receptor’s function, suggesting that external binding to the receptor is required for its activity. The cholinergic agent desformylflustrabromine counteracts the KLVFF effect. Remarkably, muscarinic receptors on dopaminergic terminals and nicotinic receptors regulating noradrenaline release in the hippocampus are completely insensitive to KLVFF. Based on our findings, KLVFF mimics Aβ1-40 as a negative modulator of specific nicotinic receptor subtypes affecting dopamine transmission in the rat brain. Therefore, new pharmacological strategies using the anti-aggregative properties of KLVFF need to be evaluated for potential interference with nicotinic receptor-mediated transmission
Synaptosomes: A Functional Tool for Studying Neuroinflammation
No full textSynaptosomes are subcellular components isolated from nerve terminations that can be prepared by homogenizing brain tissue in isotonic sucrose solution followed by appropriate centrifugation. Their preparation technique has a long history since synaptosomes were first isolated from nerve endings and described by Gray and Whittaker in 1962. The preparation of synaptosomes produces presynaptic boutons alone or in combination with fragments of postsynaptic membranes. Interestingly, synaptosomes contain organelles and vesicles that express native channels, receptors, and transporters. At 37 °C, these isolated nerve endings are metabolically active and synthesize and release neurotransmitters. They are actively used to investigate neurotransmission, its actors, and the mechanisms of neurotransmitter release. To date, many functional and non-functional applications of synaptosomes have been documented. Due to their versatility, synaptosomes have been actively used to study neuroinflammatory processes
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
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
Complement, a synaptic organizer at glutamate tripartite synapses in the cortex of mice suffering from experimental autoimmune encephalomyelitis: synaptic pruning and transmission derangements
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