Samuele Laudani

University of Catania

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Filippo Drago

University of Catania

Giuseppe Grosso

University of Catania

Justyna Godos

University of Catania

Gian Marco Leggio

University of Catania

Salvatore Salomone

University of Catania

Ida Guerrera

University of Catania

Giovanni Luca Romano

University of Catania

Sebastiano Alfio Torrisi

University of Catania

Fulvia Sinatra

University of Catania

Vincenzo Di Marzo

Istituto di Chimica Biomolecolare

Cooperative Institutions

University of Catania

Istituti di Ricovero e Cura a Carattere Scientifico

University of Bari Aldo Moro

National Research Council

National Academies of Sciences, Engineering, and Medicine

Azienda Ospedaliero-Universitaria Policlinico - Vittorio Emanuele

University of Milan

Lieber Institute for Brain Development

University of Padua

Oasi Maria SS

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Sex dimorphism controls dysbindin-related cognitive dysfunctions in mice and humans with the contribution of COMT

Molecular Psychiatry (2024)

Federica Geraci Roberta Passiatore Nora Penzel Samuele Laudani Alessandro Bertolino

Cognitive dysfunctions are core-enduring symptoms of schizophrenia, with important sex-related differences. Genetic variants of the DTBPN1 gene associated with reduced dysbindin-1 protein (Dys) expression negatively impact cognitive functions in schizophrenia through a functional epistatic interaction with Catechol-O-methyltransferase (COMT). Dys is involved in the trafficking of dopaminergic receptors, crucial for prefrontal cortex (PFC) signaling regulation. Moreover, dopamine signaling is modulated by estrogens via inhibition of COMT expression. We hypothesized a sex dimorphism in Dys-related cognitive functions dependent on COMT and estrogen levels. Our multidisciplinary approach combined behavioral-molecular findings on genetically modified mice, human postmortem Dys expression data, and in vivo fMRI during a working memory task performance. We found cognitive impairments in male mice related to genetic variants characterized by reduced Dys protein expression (p

Sexual dimorphism

Sex characteristics

10.1038/s41380-024-02527-3

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Citations (2)

Isoflavones Effects on Vascular and Endothelial Outcomes: How Is the Gut Microbiota Involved?

Pharmaceuticals (2024)

Samuele Laudani Justyna Godos Giovanni Luca Romano Lucia Gozzo Fabio Di Domenico

Isoflavones are a group of (poly)phenols, also defined as phytoestrogens, with chemical structures comparable with estrogen, that exert weak estrogenic effects. These phytochemical compounds have been targeted for their proven antioxidant and protective effects. Recognizing the increasing prevalence of cardiovascular diseases (CVD), there is a growing interest in understanding the potential cardiovascular benefits associated with these phytochemical compounds. Gut microbiota may play a key role in mediating the effects of isoflavones on vascular and endothelial functions, as it is directly implicated in isoflavones metabolism. The findings from randomized clinical trials indicate that isoflavone supplementation may exert putative effects on vascular biomarkers among healthy individuals, but not among patients affected by cardiometabolic disorders. These results might be explained by the enzymatic transformation to which isoflavones are subjected by the gut microbiota, suggesting that a diverse composition of the microbiota may determine the diverse bioavailability of these compounds. Specifically, the conversion of isoflavones in equol—a microbiota-derived metabolite—seems to differ between individuals. Further studies are needed to clarify the intricate molecular mechanisms behind these contrasting results.

Equol

Phytochemical

10.3390/ph17020236

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A novel arousal-based individual screening reveals susceptibility and resilience to PTSD-like phenotypes in mice

Neurobiology of Stress (2020)

Sebastiano Alfio Torrisi Gianluca Lavanco Oriana Maria Maurel Walter Gulisano Samuele Laudani

Translational animal models for studying post-traumatic stress disorder (PTSD) are valuable for elucidating the poorly understood neurobiology of this neuropsychiatric disorder. These models should encompass crucial features, including persistence of PTSD-like phenotypes triggered after exposure to a single traumatic event, trauma susceptibility/resilience and predictive validity. Here we propose a novel arousal-based individual screening (AIS) model that recapitulates all these features. The AIS model was designed by coupling the traumatization (24 h restraint) of C57BL/6 J mice with a novel individual screening. This screening consists of z-normalization of post-trauma changes in startle reactivity, which is a measure of arousal depending on neural circuits conserved across mammals. Through the AIS model, we identified susceptible mice showing long-lasting hyperarousal (up to 56 days post-trauma), and resilient mice showing normal arousal. Susceptible mice further showed persistent PTSD-like phenotypes including exaggerated fear reactivity and avoidance of trauma-related cue (up to 75 days post-trauma), increased avoidance-like behavior and social/cognitive impairment. Conversely, resilient mice adopted active coping strategies, behaving like control mice. We further uncovered novel transcriptional signatures driven by PTSD-related genes as well as dysfunction of hypothalamic–pituitary–adrenal axis, which corroborated the segregation in susceptible/resilient subpopulations obtained through the AIS model and correlated with trauma susceptibility/resilience. Impaired hippocampal synaptic plasticity was also observed in susceptible mice. Finally, chronic treatment with paroxetine ameliorated the PTSD-like phenotypes of susceptible mice. These findings indicate that the AIS model might be a new translational animal model for the study of crucial features of PTSD. It might shed light on the unclear PTSD neurobiology and identify new pharmacological targets for this difficult-to-treat disorder.

Traumatic stress

10.1016/j.ynstr.2020.100286

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The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology

International Journal of Molecular Sciences (2023)

Martina Di Bartolomeo Tibor Štark Serena Di Martino Fabio Arturo Iannotti Jana Kučerová

Adolescent exposure to cannabinoids as a postnatal environmental insult may increase the risk of psychosis in subjects exposed to perinatal insult, as suggested by the two-hit hypothesis of schizophrenia. Here, we hypothesized that peripubertal Δ9-tetrahydrocannabinol (aTHC) may affect the impact of prenatal methylazoxymethanol acetate (MAM) or perinatal THC (pTHC) exposure in adult rats. We found that MAM and pTHC-exposed rats, when compared to the control group (CNT), were characterized by adult phenotype relevant to schizophrenia, including social withdrawal and cognitive impairment, as revealed by social interaction test and novel object recognition test, respectively. At the molecular level, we observed an increase in cannabinoid CB1 receptor (Cnr1) and/or dopamine D2/D3 receptor (Drd2, Drd3) gene expression in the prefrontal cortex of adult MAM or pTHC-exposed rats, which we attributed to changes in DNA methylation at key regulatory gene regions. Interestingly, aTHC treatment significantly impaired social behavior, but not cognitive performance in CNT groups. In pTHC rats, aTHC did not exacerbate the altered phenotype nor dopaminergic signaling, while it reversed cognitive deficit in MAM rats by modulating Drd2 and Drd3 gene expression. In conclusion, our results suggest that the effects of peripubertal THC exposure may depend on individual differences related to dopaminergic neurotransmission.

Cognitive deficit

10.3390/ijms24043907

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Effect of a Bone Marrow-Derived Extracellular Matrix on Cell Adhesion and Neural Induction of Dental Pulp Stem Cells

Frontiers in Cell and Developmental Biology (2020)

Samuele Laudani Valentina La Cognata Rosario Iemmolo Gabriele Bonaventura Giusy Villaggio

Extracellular matrix (ECM) represents an essential component of the cellular niche. In this conditioned microenvironment, proliferation rate and differentiation states of stem cells are regulated by several factors. On the contrary, in in vitro experimental models, cell growth or induction procedures towards specific cell lines usually occur in contact with plastic, glass or biogel supports. In this study, we evaluated the effect of a decellularized ECM, derived by bone marrow stem cells, on neuronal differentiation of mesenchymal stem cells extracted from dental pulp (Dental Pulp Stem Cells - DPSCs). Since DPSCs derive from neuroectodermal embryonic precursors, they are thought to have a major propensity towards the neuronal differentiation than mesenchymal stem cells isolated from other sources. We hypothesized that the presence of a decellularized ECM scaffold could act positively on neuronal-DPSCs differentiation through reproduction of an in vivo-like microenvironment. Results from scanning electron microscopy, immunofluorescence and gene expression assays showed that ECM is able to positively influence the morphology of cells, their distribution and the expression of specific neuronal markers (i.e. NF-L, NF-M, NF-H, PAX6, MAP2).

Decellularization

10.3389/fcell.2020.00100

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Citations (27)

Food security and Mediterranean diet in five countries: the DELICIOUS project

European Journal of Public Health (2023)

Justyna Godos Ida Guerrera Samuele Laudani António Mata María Isabel Pardo

Abstract Food security is a universal need assuring access to healthy diet in both developing and developed countries. The aim of this study was to investigate the association between factors related to food security and adherence to the Mediterranean diet in 5 Mediterranean countries (Italy, Spain, Portugal, Egypt, and Lebanon) participating to the EU funded project DELICIOUS (UnDErstanding consumer food choices & promotion of healthy and sustainable Mediterranean diet and LIfestyle in Children and adolescents through behavIOUral change actionS). Data were retrieved from a survey involving 2011 parents of children and adolescents aged 6-17 years old. The KIDMED score was used to assess the level of adherence to the Mediterranean diet. Information regarding easiness to retrieve foods characteristic of the Mediterranean diet, working status, economic allowance, and place of living were collected. The association with adherence to the Mediterranean diet were investigated by performing logistic regressions. The analyses revealed that individuals living in rural areas and reporting difficulty to retrieve all food items explored were less likely to have higher adherence to the Mediterranean diet. Moreover, higher adherence was also associated with household income higher than €3,500. No associations with family status nor working situation were found. There were no evident differences across countries, although there was nearly an inverse trend toward lack of association between economic allowance and higher adherence to the Mediterranean diet in Italy. In conclusion, the progressive abandonment of traditional dietary patterns, such as the Mediterranean diet, may not just depend on a cultural shift toward unhealthier industrial alternatives, but also on family budget and easiness to retrieve food stuff. Key messages • Food security may play a role in adherence to the Mediterranean diet. • The food market may be responsible for changes in cultural culinary habits.

Mediterranean Diet

Promotion (chess)

Allowance (engineering)

10.1093/eurpub/ckad160.1087

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Adolescent THC exposure differentially affects behavioural and molecular alterations caused by neurodevelopmental insults

Neuroscience Applied (2023)

S. Di Martino M. Di Bartolomeo T. Stark F.A. Iannotti J. Ruda-Kucerova

10.1016/j.nsa.2023.101064

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Study of a Miniaturizable System for Optical Sensing Application to Human Cells

Applied Sciences (2019)

Emanuele Luigi Sciuto Giusy Villaggio Maria Francesca Santangelo Samuele Laudani Concetta Federico

Conventional approaches to human intracellular optical sensing, generally, require dedicated laboratories with bulky detection systems. They are performed by cell labeling procedures based on the use of fluorophores that are, mostly, phototoxic, invasive, bleached in case of prolonged light exposures, which require carriers and/or structural modifications for the cellular uptake. These issues, together with the sensitivity of the eukaryotic cell model, could be problematic towards the development of a robust sensing system suitable for biomedical screening. In this work, we studied a sensing system resulting from the combination of the commercial tris(2,2’bipyridyl)ruthenium(II) fluorophore, for cell labeling, with a potentially miniaturizable optical system composed by a laser source and a photomultiplier tube, for the fluorescence analysis.

Optical sensing

10.3390/app9050975

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Citations (7)

Flavan-3-ols and Vascular Health: Clinical Evidence and Mechanisms of Action

Nutrients (2024)

Justyna Godos Giovanni Luca Romano Samuele Laudani Lucia Gozzo Ida Guerrera

Cardiovascular diseases (CVDs) are one of the main causes of mortality and morbidity worldwide. A healthy diet rich in plant-derived compounds such as (poly)phenols appears to have a key role in improving cardiovascular health. Flavan-3-ols represent a subclass of (poly)phenols of great interest for their possible health benefits. In this review, we summarized the results of clinical studies on vascular outcomes of flavan-3-ol supplementation and we focused on the role of the microbiota in CVD. Clinical trials included in this review showed that supplementation with flavan-3-ols mostly derived from cocoa products significantly reduces blood pressure and improves endothelial function. Studies on catechins from green tea demonstrated better results when involving healthy individuals. From a mechanistic point of view, emerging evidence suggests that microbial metabolites may play a role in the observed effects. Their function extends beyond the previous belief of ROS scavenging activity and encompasses a direct impact on gene expression and protein function. Although flavan-3-ols appear to have effects on cardiovascular health, further studies are needed to clarify and confirm these potential benefits and the rising evidence of the potential involvement of the microbiota.

Flavan

Cardiovascular Health

Health Benefits

Lower blood pressure

10.3390/nu16152471

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Citations (4)

Gut-liver axis: may prebiotics play a role?

International Journal of Food Sciences and Nutrition (2023)

Samuele Laudani Giuseppe Grosso

10.1080/09637486.2023.2274274

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Citations (0)