258 research outputs found
INVOLVEMENT OF OXIDATIVE BALANCE IN THE ETIOLOGY, PATHOPHYSIOLOGY AND TREATMENT OF STRESS-RELATED PSYCHIATRIC DISORDERS
No full textPsychiatric disorders are severe and heterogeneous pathologies affecting an individual’s cognition, emotional regulation and behaviour. In 2019, 1 over 8 people was living with a mental illness, with major depressive disorder (MDD) identified as the leading global cause of disability, and with the spread of COVID-19 there has been a strong increase in the prevalence of MDD, anxiety disorder (AD) and eating disorders (ED). Moreover, the pharmacological treatment of psychopathologies is still largely ineffective and presents several critical aspects, such as the latency of therapeutic effects and the number of non-responder patients. On these bases, it is crucial to study psychiatric disorders to identify new molecular systems involved in their pathophysiology, with the aim to develop novel pharmacological strategies. In this context, to help the diagnosis and treatment of such pathologies, and based on the fact that some features are shared among the different pathologies, the Research Domain Criteria (RDoC) initiative has been launched by the National Institute of Mental Health. Indeed, the aetiology of many different psychiatric disorders relies on the same basis: the interaction between susceptibility genes and environmental stimuli, with the most important one being stress. Of course, it must be considered that not all the subjects exposed to stress will develop a psychopathology, and that not all types of stressors have detrimental effects on the organism. Indeed, acute stressors can be considered a fuel for the brain and body, helping to achieve expected results, however, if the stressors persist for longer periods, are too intense, or the molecular underpinnings of the body response have been primed to a maladaptive response by genetic or environmental backgrounds, the outcome of stress could be pathological. Moreover, although particularly defining for MDD, another common feature among different psychiatric diseases is the symptom of anhedonia, the inability to experience pleasure in situations considered satisfying. These common aspects are exploited by researchers and clinicians to study and understand them. Thus, my PhD project aims to study, at preclinical level, the molecular effects produced by different types of stress. In order to do so, I exploited different types and combination of stressors, such as the Chronic Mild Stress (CMS) model of depression, combined with acute physical (restraint stress) and inflammatory (lipopolysaccharide or LPS) challenges, and the Activity-Based Anorexia (ABA) model of anorexia nervosa, focusing on the involvement of oxidative balance, investigated mainly at mRNA and protein levels in such aspects. The choice of this molecular system relies on the fact that the brain requires a lot of energy -that is a generator of oxidative stress- to support neuronal activity, and on the fact that oxidative stress could act as a bridge between neuroinflammation and the dysregulation in synaptic processes (i.e. neurotransmitter and receptors expression and/or function, signalling pathways), both important players in the neurobiology of psychiatric disorders. Considering the choice of the CMS paradigm, it is important to underline that this model is able to produce two different subpopulations of stressed animals: the vulnerable one, that develops the anhedonic -depressive-like- phenotype and the resilient one that, despite stress exposure, does not, and this has a great translational value and allowed us to study, at molecular level, also the population that is not susceptible to stress exposure.
The results of my PhD project revealed that oxidative balance is crucial for the proper stress response. Indeed, stress exposure was able to cause oxidative stress in different areas of the CNS of vulnerable animals, but not of resilient ones. This derangement is accompanied by a malfunctioning of the antioxidant pathway of Nrf2, modulation that is once again specific for vulnerable animals, as opposed to resilient ones that showed an increased activation of the antioxidant system. Moreover, the derangement produced by CMS, are exacerbated after a further acute inflammatory challenge, in response to which stress-vulnerable animals showed even higher levels of oxidative stress. In addition, I also demonstrated a role for the antioxidant machinery in the acute stress-response (through the gene expression analysis of different antioxidant enzymes), and its destabilization in chronically stressed animals. We also found that the pharmacological treatments examined (chronic administrations of antipsychotics blonanserin and lurasidone) were able –at least in part and in an anatomical –specific manner- to prevent the negative effects of chronic stress and to re-establish the proper acute response in stressed animals. Finally, the analyses conducted in the ABA model of anorexia nervosa revealed that also in this case the oxidative balance is affected by the stressful experimental paradigm. Considering the very few information available about this model and about anorexia nervosa patients, we expanded our research also to neuroinflammation, with whom it has a very well-known crosstalk, and to neuroplasticity, an important process that is often impaired in psychiatric conditions. We observed that in this early phase of the pathology there is still an adaptive/compensatory response of the animals and a strong effect of the single components of the paradigm, therefore, future studies are necessary to deeply understand the involvement of the molecular systems considered.
The results obtained in this thesis indicates a clear involvement of oxidative balance and other systems related to it in the pathophysiology of psychiatric disorders. Indeed, the anhedonic behavior is characterized by an unbalanced equilibrium between pro- and antioxidant factors, that participates in the impaired ability of those animals to respond to subsequent challenges. The pharmacological treatment is able, at least in part, to re-establish the correct oxidative balance, that might therefore represent an important target to take into consideration to improve the pharmacotherapy of psychiatric disorders, however, more studies are necessary to prove the behavioral and molecular effects of compounds able to act directly on the antioxidant machinery
Erratum: Lack of immunity against rubella among Italian young adults. [BMC Infect Dis., 17, (2017) (199)] Doi: 10.1186/s12879-017-2295-y
No full textAfter publication of this article [1], the authors noted that the given names and family names of all authors had been inverted, and are therefore incorrect in the original article. In the original article, the author names appear as the following: Gallone Maria Serena, Gallone Maria Filomena, Larocca Angela Maria Vittoria, Germinario Cinzia and Tafuri Silvio. However, this is incorrect, and the author names should appear as per the below: Maria Serena Gallone, Maria Filomena Gallone, Angela Maria Vittoria Larocca, Cinzia Germinario, Silvio Tafuri. The author names have been corrected in the author list and the citation for this Erratum
The Translator as Writer
No full textThis volume is a collection of studies on authorship in translation. Leading translation scholars and professional translators discuss the theoretical implications and applicability of the author-translator paradigm. The relationship between translators and authors is addressed in its various manifestations, from the author-translator collaboration, to self-translation, to authorial practices of translating
Le Memorie, archivio aperto
No full textIl contributo delinea il percorso di ricerca seguito dall'autore relativo all'edizione digitale del lavoro a stampa: Memorie su le antiche case di Udine di Giovanni Battista della Porta, a cura di Vittoria Masutti (1984-1987) | The paper describes the research work carried out by the author, concerning the digital edition of the volume Memorie su le antiche case di Udine di Giovanni Battista della Porta, edited by Vittoria Masutti (1984-1987
Activity-based anorexia (ABA) model: Effects on brain neuroinflammation, redox balance and neuroplasticity during the acute phase
No full textSeveral evidences suggest that immuno-inflammatory responses are involved in the pathogenesis of anorexia nervosa (AN). Herein we investigate the possible alteration of key mediators of inflammation, redox balance, and neuroplasticity in the brain of rats showing an anorexic-like phenotype. We modeled AN in adolescent female rats using the activity-based anorexia (ABA) paradigm and measured gene expression levels of targets of interest in the prefrontal cortex (PFC) and dorsal hippocampus (DH). We observed reduced mRNA levels of proinflammatory cytokines IL-1(3 and TNF-alpha, the inflammasome NLRP3, and the microglial marker CD11b in both PFC and DH of ABA animals. Conversely, the mRNA of IL-6, which acts as both a pro-inflammatory and antiinflammatory cytokine, was increased. Moreover, we observed an overall upregulation of different antioxidant enzymes in PFC, while their profile was not affected or opposite in the DH, with the exception of MT1 alpha. Interestingly, ABA animals showed elevated levels of the neuroplasticity marker BDNF in both PFC and DH. Our data indicate that ABA induction is associated with anatomical-specific cerebral alteration of mediators of neuroinflammation, oxidative balance and neuroplasticity. Although more research should be conducted, these results add important information about the role of these systems in the complex AN etiopathogenesis
Author response: Do high mtDNA copy numbers truly prevent LHON manifestations?
No full textNot availabl
Pensionati recalcitranti e discriminazione fondata sull’età
No full textThe essay is devoted to age discrimination, with special regard to elderly employees. The author starts from the question whether, and in what limits, the aspiration of elderly employees to retain their jobs after the reaching of retirement age is protected by EU discrimination law. In order to answer the question, she preliminarily focuses on the ECG case law, approaching some theoretical issues, emerging in the Mangold and Kücükdeci decisions: mainly, the controversial horizontal effects of general principles and the also controversial direct effect of the directives that implement general principles. In the second part of the essay, the author develops a critical analysis of the arguments on the basis of which the ECG justifies the measures of compulsory retirement adopted by the member States. She criticizes the use of the reference to the occupational policy, too generic, as well as the under evaluation of the proportionality test
Astuzie e ingenuità di una clausola singolare
No full textThis essay focuses on the clause of industrial peace obligation provided by company-wide collective agreements of Pomigliano, Mirafiori and Fabbrica Italia Pomigliano (but the last one aims to become the new national car sector collective agreement). The clause is critically analysed first of all with regard to unions’ responsibility. Such a responsibility results from the subscription of an obligation of industrial peace which compels unions to abstain from calling industrial action (strike and other struggle forms), in order to ensure a peaceful or no conflicting implementation of the agreement, and thereby work and production continuity. The author considers this extent of peace obligation to be abnormal and not compatible with workers’ protection function of the unions. Moreover, the author critically analyses the union peace clause from the stand point of his incidence on workers’ right to strike. The author shares the dominant thesis according to which the right to strike is an individual one; so she thinks that the strike of workers in industrial peace clause violation is fully legal
Le sentenze Viking e Laval: la Corte di giustizia “bilancia” il diritto di sciopero
No full textThe essay analyses the ECJ decisions Viking and Laval where the court was called to answer the question of her jurisdiction upon trade unions freedom of association and the right to take industrial action. The Author focuses on the court’s rationale with special regard to the following statements: (a) the horizontal effect of ECT articles 43 (freedom of establishment) and 49 (freedom of providing services), according to which private undertakings can rely upon free movement provisions against trade unions, since industrial action aims at concluding collective agreements and collective agreements fall within the scope of free movement provisions; (b) the right to take industrial action amounts at a fundamental right guaranteed by community law, but at the same time it also constitutes a restriction upon fundamental economic freedom, and it is a competence of the ECJ to strike a balance between them; (c) as far as the balancing between free movement and industrial action is concerned, industrial action, even when justified by the legitimate (non discriminatory) aim of workers protection, is subject to the proportionality test.
A critical analysis of the above mentioned statements leads the Author to conclude the essay with some remarks on the theoretical and practical consequences of the ECJ interference in the balancing of “internal” constitutional values
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