75 research outputs found
Infarto miocardico acuto associato a vasospasmo coronarico ‘‘tardivo’’ in un paziente sottoposto a trapianto cardiaco.
No full textVery late coronary spasm inducing acute myocardial infarction in a heart transplant recipient.
No full textMolecular underpinnings of programming by early-life stress and the protective effects of early dietary ω6/ω3 ratio, basally and in response to LPS: Integrated mRNA-miRNAs approach
No full textEarly-life stress (ELS) exposure increases the risk for mental disorders, including cognitive impairments later in life. We have previously demonstrated that an early diet with low ω6/ω3 polyunsaturated fatty acid (PUFA) ratio protects against ELS-induced cognitive impairments. Several studies have implicated the neuroimmune system in the ELS and diet mediated effects, but currently the molecular pathways via which ELS and early diet exert their long-term impact are not yet fully understood. Here we study the effects of ELS and dietary PUFA ratio on hippocampal mRNA and miRNA expression in adulthood, both under basal as well as inflammatory conditions. Male mice were exposed to chronic ELS by the limiting bedding and nesting material paradigm from postnatal day(P)2 to P9, and provided with a diet containing a standard (high (15:1.1)) or protective (low (1.1:1)) ω6 linoleic acid to ω3 alpha-linolenic acid ratio from P2 to P42. At P120, memory was assessed using the object location task. Subsequently, a single lipopolysaccharide (LPS) injection was given and 24 h later hippocampal genome-wide mRNA and microRNA (miRNA) expression was measured using microarray. Spatial learning deficits induced by ELS in mice fed the standard (high ω6/ω3) diet were reversed by the early-life protective (low ω6/ω3) diet. An integrated miRNA - mRNA analysis revealed that ELS and early diet induced miRNA driven mRNA expression changes into adulthood. Under basal conditions both ELS and the diet affected molecular pathways related to hippocampal plasticity, with the protective (low ω6/ω3 ratio) diet leading to activation of molecular pathways associated with improved hippocampal plasticity and learning and memory in mice previously exposed to ELS (e.g., CREB signaling and endocannabinoid neuronal synapse pathway). LPS induced miRNA and mRNA expression was strongly dependent on both ELS and early diet. In mice fed the standard (high ω6/ω3) diet, LPS increased miRNA expression leading to activation of inflammatory pathways. In contrast, in mice fed the protective diet, LPS reduced miRNA expression and altered target mRNA expression inhibiting inflammatory signaling pathways and pathways associated with hippocampal plasticity, which was especially apparent in mice previously exposed to ELS. This data provides molecular insights into how the protective (low ω6/ω3) diet during development could exert its long-lasting beneficial effects on hippocampal plasticity and learning and memory especially in a vulnerable population exposed to stress early in life, providing the basis for the development of intervention strategies
miRNAs in depression vulnerability and resilience: novel targets for preventive strategies
No full textThe exposure to stressful experiences during the prenatal period and through the first years of life is known to affect the brain developmental trajectories, leading to an enhanced vulnerability for the development of several psychiatric disorders later in life. However, not all the subjects exposed to the same stressful experience develop a pathologic condition, as some of them, activating coping strategies, become more resilient. The disclosure of mechanisms associated with stress vulnerability or resilience may allow the identification of novel biological processes and potential molecules that, if properly targeted, may prevent susceptibility or potentiate resilience. Over the last years, miRNAs have been proposed as one of the epigenetic mechanisms mediating the long-lasting effects of stress. Accordingly, they are associated with the development of stress vulnerability or resilience-related strategies. Moreover, miRNAs have been proposed as possible biomarkers able to identify subjects at high risk to develop depression and to predict the response to pharmacological treatments. In this review, we aimed to provide an overview of findings from studies in rodents and humans focused on the involvement of miRNAs in the mechanisms of stress response with the final goal to identify distinct sets of miRNAs involved in stress vulnerability or resilience. In addition, we reviewed studies on alterations of miRNAs in the context of depression, showing data on the involvement of miRNAs in the pathogenesis of the disease and in the efficacy of pharmacological treatments, discussing the potential utility of miRNAs as peripheral biomarkers able to predict the treatment response
The Complex Molecular Picture of Gut and Oral Microbiota–Brain-Depression System: What We Know and What We Need to Know
No full textMajor depressive disorder (MDD) is a complex mental disorder where the neurochemical, neuroendocrine, immune, and metabolic systems are impaired. The microbiota-gut-brain axis is a bidirectional network where the central and enteric nervous systems are linked through the same endocrine, immune, neural, and metabolic routes dysregulated in MDD. Thus, gut-brain axis abnormalities in MDD patients may, at least in part, account for the symptomatic features associated with MDD. Recent investigations have suggested that the oral microbiome also plays a key role in this complex molecular picture of relationships. As on one hand there is a lot of what we know and on the other hand little of what we still need to know, we structured this review focusing, in the first place, on putting all pieces of this complex puzzle together, underlying the endocrine, immune, oxidative stress, neural, microbial neurotransmitters, and metabolites molecular interactions and systems lying at the base of gut microbiota (GM)–brain-depression interphase. Then, we focused on promising but still under-explored areas of research strictly linked to the GM and potentially involved in MDD development: (i) the interconnection of GM with oral microbiome that can influence the neuroinflammation-related processes and (ii) gut phageome (bacteria-infecting viruses). As conclusions and future directions, we discussed potentiality but also pitfalls, roadblocks, and the gaps to be bridged in this exciting field of research. By the development of a broader knowledge of the biology associated with MDD, with the inclusion of the gut/oral microbiome, we can accelerate the growth toward a better global health based on precision medicine
Social isolation in adolescence and long-term changes in the gut microbiota composition and in the hippocampal inflammation: Implications for psychiatric disorders – Dirk Hellhammer Award Paper 2021
No full textExposure to early adverse experiences induces persistent changes in physiological, emotional and behavioural
functions predisposing the individual to an enhanced vulnerability to develop different disorders during lifespan.
The adverse outcomes depend upon the timing of the stressful experiences, and in this contest, adolescence
represents a key sensitive period for brain development. Among the biological systems involved, gut microbiota
has recently been proposed to act on the interplay between the stress response, brain functions and immune
system, through the gut-brain axis communication.
In the current study we aimed to evaluate, in a preclinical model, changes over time in the microbiota
community structure in physiological condition and in response to stress during adolescence. We also aimed to
correlate the microbiota composition to the inflammatory status in brain.
We used the preclinical model of social deprivation in rats during adolescence, based on the lack of all social
contacts, for four weeks after weaning, followed by re-socialization until adulthood. We collected fecal samples
at different post-natal days to investigate the short- and long-lasting effects of social isolation on gut microbiota
composition and we collected brain areas (dorsal and ventral hippocampus) samples at killing to measure a panel
of inflammatory and microglia activation markers.
16 S metataxonomic sequencing analysis revealed that microbial changes were influenced by age in both
isolated and controls rats, regardless of sex, whereas social isolation impacted the microbial composition in a sex-
dependent manner. A multivariate analysis showed that social isolation induced short-term gut microbiota al-
terations in females but not in males. We also identified several stress-related genera associated with social
isolation condition. In brain areas we found a specific inflammatory pattern, in dorsal and ventral hippocampus,
that significantly correlated with gut microbiota composition.
Overall, in this study we reported a novel sex-specific association between gut microbiota composition and
inflammatory response related to social isolation paradigm during adolescence, suggesting that stressful expe-
riences during this sensitive period could have a long-lasting impact on the development of different biological
systems that could in turn influence the vulnerability to develop mental disorders later in life
Emotional Regulation in Teens and Improvement of Constructive Skills (EmoTIConS): study protocol for a randomized controlled trial
No full textBackground: Emotional dysregulation (ED) constitutes a relevant factor involved in the onset and maintenance of many mental disorders. Targeting ED during adolescence could be a determinant both to identify high-risk individuals and to promote preventive interventions. This study will aim to evaluate the impact of a brief Dialectical Behavioral Therapy (DBT)-based intervention for adolescent students by measuring changes in emotional regulation skills and impulsive behaviors. Moreover, alterations in biological features related to stress response and inflammation will be assessed as potential biological variables associated with ED. Methods: This is a randomized trial. A total of 20 classes of adolescent students will be recruited among high schools in Brescia, a city in northern Italy. They will be randomized to the psychoeducational intervention (experimental group) or to a control condition (control group). The intervention will be based on DBT Skills Training for Emotional Problem Solving for Adolescents, and will consist of four monthly, 2-h sessions (for a total of 8 h) scheduled during regular school time. Participants will be assessed at baseline, post-intervention, and at 3 and 6 months of follow-up. The primary outcome measures will be represented by changes in the use of emotional regulation skills and by changes in the frequency of impulsive behaviors. Salivary samples will be collected at baseline and post-intervention to explore possible biological features underlying ED. Discussion: Data from the present project will offer the opportunity to better understand the complex phenomenon of ED. Repeated assessment will cover several domains (emotional, behavioral, social, biological) as potential factors associated with ED. Moreover, it will be possible to establish the effect of the proposed intervention, thus helping to improve knowledge on the impact of school-based universal preventive programs. Finally, the current trial will propose an integrated screening and intervention-based model. Ultimately, this could reduce barriers to youths’ mental health care by fostering collaboration between schools and mental health services. Trial registration: ClinicalTrials.gov NCT04349709. Registered on April 16, 2020
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