Scientific Institute IRCCS Eugenio Medea

Bosisio Parini, Italy

Scientific Institute IRCCS Eugenio Medea

Bosisio Parini, Italy
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Perrotta C.,University of Milan | De Palma C.,University of Milan | Clementi E.,University of Milan | Clementi E.,Scientific Institute IRCCS Eugenio Medea | And 2 more authors.
Frontiers in Cellular Neuroscience | Year: 2015

Accumulating evidence indicates that the endocrine and immune systems engage in complex cross-talks in which a prominent role is played by thyroid hormones (THs). The increase of resident vs. monocyte recruited macrophages was shown to be an important effector of the TH 3,3′,5′-Triiodo-L-thyronine (T3)-induced protection against inflammation and a key role of T3 in inhibiting the differentiation of peripheral monocytes into macrophages was observed. Herein, we report on the role of T3 as a modulator of microglia, the specialized macrophages of the central nervous system (CNS). Mounting evidence supports a role of microglia and macrophages in the growth and invasion of malignant glioma. In this respect, we unveil the putative involvement of T3 in the microglia/glioma cell communication. Since THs are known to cross the blood-brain barrier, we suggest that T3 not only exerts a direct modulation of brain cancer cell itself but also indirectly promotes glioma growth through a modulation of microglia. Our observations expand available information on the role of TH system in glioma and its microenvironment and highlight the endocrine modulation of microglia as an important target for future therapeutic development of glioma treatments. © 2015, Perrotta, De Palma, Clementi and Cervia.


Piazza C.,Polytechnic of Milan | Piazza C.,Scientific Institute IRCCS Eugenio Medea | Cantiani C.,Scientific Institute | Akalin-Acar Z.,University of California at San Diego | And 5 more authors.
NeuroImage | Year: 2016

The abilities of infants to perceive basic acoustic differences, essential for language development, can be studied using auditory event-related potentials (ERPs). However, scalp-channel averaged ERPs sum volume-conducted contributions from many cortical areas, reducing the functional specificity and interpretability of channel-based ERP measures. This study represents the first attempt to investigate rapid auditory processing in infancy using independent component analysis (ICA), allowing exploration of source-resolved ERP dynamics and identification of ERP cortical generators. Here, we recorded 60-channel EEG data in 34 typically developing 6-month-old infants during a passive acoustic oddball paradigm presenting 'standard' tones interspersed with frequency- or duration-deviant tones. ICA decomposition was applied to single-subject EEG data. The best-fitting equivalent dipole or bilaterally symmetric dipole pair was then estimated for each resulting independent component (IC) process using a four-layer infant head model. Similar brain-source ICs were clustered across subjects. Results showed ERP contributions from auditory cortex and multiple extra-auditory cortical areas (often, bilaterally paired). Different cortical source combinations contributed to the frequency- and duration-deviant ERP peak sequences. For ICs in an ERP-dominant source cluster located in or near the mid-cingulate cortex, source-resolved frequency-deviant response N2 latency and P3 amplitude at 6 months-of-age predicted vocabulary size at 20 months-of-age. The same measures for scalp channel F6 (though not for other frontal channels) showed similar but weaker correlations. These results demonstrate the significant potential of ICA analyses to facilitate a deeper understanding of the neural substrates of infant sensory processing. © 2016 Elsevier Inc.


Casartelli L.,University of Geneva | Casartelli L.,Scientific Institute IRCCS Eugenio MEDEA | Casartelli L.,Vita-Salute San Raffaele University | Chiamulera C.,University of Verona
Cognitive, Affective and Behavioral Neuroscience | Year: 2016

To understand others’ minds is crucial for survival; however, it is quite puzzling how access to others’ minds can be—to some extent—direct and not necessarily mediated by conceptual reasoning. Recent advances in neuroscience have led to hypothesize a role for motor circuits not only in controlling the elementary physical features of movement (e.g., force, direction, and amplitude), but also in understanding and shaping human behavior. The concept of “motor cognition” refers to these aspects, and neurophysiological, neuroimaging, and behavioral studies in human and nonhuman primates support this view. From a clinical perspective, motor cognition represents a challenge in several domains. A thorough investigation of the neural mechanisms mediating motor action/intention understanding and automatized/compulsive behaviors seems to be a promising way to tackle a range of neurodevelopmental and drug-related disorders. On the one hand, anomalies in motor cognition may have cascade effects on social functioning in individuals with autism spectrum disorder (ASD); on the other, motor cognition may help explain the pathophysiology of drug-seeking and drug-taking behaviors in the most severe phase of drug addiction (i.e., see drug dependence, motor low-order cue reactivity). This may represent a promising approach that could improve the efficacy of rehabilitative interventions. The only way to shed light on multifactorial disorders such as ASD and drug addiction is through the investigation of their multiple factors. This motor way can promote new theoretical and experimental perspectives that would help bridge the gap between the basic neuroscience approach and clinical practice. © 2015, Psychonomic Society, Inc.


Kirsch L.P.,Bangor University | Kirsch L.P.,University College London | Urgesi C.,Bangor University | Urgesi C.,University of Udine | And 3 more authors.
Neuroscience and Biobehavioral Reviews | Year: 2016

Less than two decades after its inception, the burgeoning field of neuroaesthetics continues to grow in interest and momentum. Despite the biological and social importance of the human body and the attention people pay to its appearance in daily life, only recently has neuroaesthetic inquiry turned its attention to questions concerning the aesthetic appraisal of the human body. We review evidence illustrating that the complexity of aesthetic experience is reflected by dynamic interplay between brain systems involved in reward, perceptual and motor processing, with a focus on aesthetic perception involving the human body. We then evaluate work demonstrating how these systems are modulated by beholders' expertise or familiarity. Finally, we discuss seminal studies revealing the plasticity of behavioural and neural responses to beauty after perceptual and motor training. This research highlights the rich potential for neuroaesthetic inquiry to extend beyond its typical realm of the fine arts to address important questions regarding the relationship between embodiment, aesthetics and performing arts. We conclude by considering some of the criticisms and limitations of neuroaesthetics, and highlight several outstanding issues for future inquiry. © 2016 The Authors.


Provenzi L.,Scientific Institute IRCCS Eugenio Medea | Giorda R.,Scientific Institute IRCCS Eugenio Medea | Beri S.,Scientific Institute IRCCS Eugenio Medea | Montirosso R.,Scientific Institute IRCCS Eugenio Medea
Neuroscience and Biobehavioral Reviews | Year: 2016

The application of epigenetics to the study of behavioral and socio-emotional development in humans has revealed that DNA methylation could be a potential marker of adversity exposure and long-lasting programming of health and disease. The serotonin transporter gene (SLC6A4) is a stress-related gene which has well-documented implications for behavioral and socio-emotional development and which has been shown to be susceptible to transcriptional regulation via epigenetic mechanisms. In the present paper, a systematic review of papers assessing the association among adversity exposures, SLC6A4 methylation and developmental outcomes is reported. Nineteen studies were included. Findings revealed that SLC6A4 methylation has been investigated in humans in association with a number of prenatal and postnatal adverse exposures, encompassing maternal depression during pregnancy, perinatal stress exposure, childhood trauma and abuse, and environmental stress. SLC6A4 is confirmed as a relevant biomarker of early adversity exposures, and epigenetic mechanisms occurring at this gene appear to play a critical role for programming. Nonetheless, specific methodological issues still need to be addressed in future human behavioral epigenetic research. © 2016 Elsevier Ltd


Abreu A.M.,Santa Lucia Foundation | Abreu A.M.,University of Rome La Sapienza | Abreu A.M.,University of Lisbon | Macaluso E.,Santa Lucia Foundation | And 7 more authors.
European Journal of Neuroscience | Year: 2012

The ability to predict the actions of others is quintessential for effective social interactions, particularly in competitive contexts (e.g. in sport) when knowledge about upcoming movements allows anticipating rather than reacting to opponents. Studies suggest that we predict what others are doing by using our own motor system as an internal forward model and that the fronto-parietal action observation network (AON) is fundamental for this ability. However, multiple-duty cells dealing with action perception and execution have been found in a variety of cortical regions. Here we used functional magnetic resonance imaging to explore, in expert basketball athletes and novices, whether the ability to make early predictions about the fate of sport-specific actions (i.e. free throws) is underpinned by neural regions beyond the classical AON. We found that, although involved in action prediction, the fronto-parietal AON was similarly activated in novices and experts. Importantly, athletes exhibited relatively greater activity in the extrastriate body area during the prediction task, probably due to their expert reading of the observed action kinematics. Moreover, experts exhibited higher activation in the bilateral inferior frontal gyrus and in the right anterior insular cortex when producing errors, suggesting that they might become aware of their own errors. Correct action prediction induced higher posterior insular cortex activity in experts and higher orbito-frontal activity in novices, suggesting that body awareness is important for performance monitoring in experts, whereas novices rely more on higher-order decision-making strategies. This functional reorganization highlights the tight relationship between action anticipation, error awareness and motor expertise leading to body-related processing and differences in decision-making processes. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.


Ronconi L.,University of Padua | Ronconi L.,Scientific Institute IRCCS Eugenio Medea | Casartelli L.,Scientific Institute IRCCS Eugenio Medea | Casartelli L.,Vita-Salute San Raffaele University | And 5 more authors.
Cerebral cortex (New York, N.Y. : 1991) | Year: 2017

In the last two decades, an intriguing shift in the understanding of the cerebellum has led to consider the nonmotor functions of this structure. Although various aspects of perceptual and sensory processing have been linked to the cerebellar activity, whether the cerebellum is essential for binding information from different sensory modalities remains uninvestigated. Multisensory integration (MSI) appears very early in the ontogenesis and is critical in several perceptual, cognitive, and social domains. For the first time, we investigated MSI in a rare case of cerebellar agenesis without any other associated brain malformations. To this aim, we measured reaction times (RTs) after the presentation of visual, auditory, and audiovisual stimuli. A group of neurotypical age-matched individuals was used as controls. Although we observed the typical advantage of the auditory modality relative to the visual modality in our patient, a clear impairment in MSI was found. Beyond the obvious prudence necessary for inferring definitive conclusions from this single-case picture, this finding is of interest in the light of reduced MSI abilities reported in several neurodevelopmental and psychiatric disorders-such as autism, dyslexia, and schizophrenia-in which the cerebellum has been implicated. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.


MacHado L.R.,University of Leicester | Hardwick R.J.,University of Leicester | Hardwick R.J.,Wellcome Trust Sanger Institute | Bowdrey J.,University of Leicester | And 5 more authors.
American Journal of Human Genetics | Year: 2012

Both sequence variation and copy-number variation (CNV) of the genes encoding receptors for immunoglobulin G (Fcγ receptors) have been genetically and functionally associated with a number of autoimmune diseases. However, the molecular nature and evolutionary context of this variation is unknown. Here, we describe the structure of the CNV, estimate its mutation rate and diversity, and place it in the context of the known functional alloantigen variation of these genes. Deletion of Fcγ receptor IIIB, associated with systemic lupus erythematosus, is a result of independent nonallelic homologous recombination events with a frequency of approximately 0.1%. We also show that pathogen diversity, in particular helminth diversity, has played a critical role in shaping the functional variation at these genes both between mammalian species and between human populations. Positively selected amino acids are involved in the interaction with IgG and include some amino acids that are known polymorphic alloantigens in humans. This supports a genetic contribution to the hygiene hypothesis, which states that past evolution in the context of helminth diversity has left humans with an array of susceptibility alleles for autoimmune disease in the context of a helminth-free environment. This approach shows the link between pathogens and autoimmune disease at the genetic level and provides a strategy for interrogating the genetic variation underlying autoimmune-disease risk and infectious-disease susceptibility. © 2012 by The American Society of Human Genetics. All rights reserved.


Rovere-Querini P.,San Raffaele Scientific Institute | Clementi E.,Scientific Institute IRCCS Eugenio Medea | Clementi E.,National Research Council Italy | Brunelli S.,San Raffaele Scientific Institute | Brunelli S.,University of Milan Bicocca
European Journal of Pharmacology | Year: 2014

Muscular dystrophies comprise an heterogeneous group of diseases characterised by primary wasting of skeletal muscle, in the most severe forms leading to progressive paralysis and death. Current therapies for these conditions are extremely limited and based on corticosteroids that bear significant side effects. Several studies have proposed possible alternative strategies, ranging from cell and gene therapy to more classical pharmacological approaches. Nitric oxide is a gaseous messenger involved in many mechanisms responsible for preserving muscle function and stimulating muscle repair. We herein review the most recent pre-clinical and clinical findings that open new prospective for the development of nitric oxide as a therapeutic tool for muscular dystrophies. © 2013 Elsevier B.V.


De Palma C.,University of Milan | Perrotta C.,University of Milan | Pellegrino P.,University of Milan | Clementi E.,University of Milan | And 3 more authors.
Frontiers in Aging Neuroscience | Year: 2014

Muscular dystrophies are a group of genetic and heterogeneous neuromuscular disorders characterised by the primary wasting of skeletal muscle. In Duchenne muscular dystrophy (DMD), the most severe form of these diseases, the mutations in the dystrophin gene lead to muscle weakness and wasting, exhaustion of muscular regenerative capacity and chronic local inflammation leading to substitution of myofibres by connective and adipose tissue. DMD patients suffer of continuous and progressive skeletal muscle damage followed by complete paralysis and death, usually by respiratory and/or cardiac failure. No cure is yet available, but several therapeutic approaches aiming at reversing the ongoing degeneration have been investigated in preclinical and clinical settings. The autophagy is an important proteolytic system of the cell and has a crucial role in the removal of proteins, aggregates and organelles. Autophagy is constantly active in skeletal muscle and its role in tissue homeostasis is complex: at high levels it can be detrimental and contribute to muscle wasting; at low levels it can cause weakness and muscle degeneration, due to the unchecked accumulation of damaged proteins and organelles. The causal relationship between DMD pathogenesis and dysfunctional autophagy has been recently investigated. At molecular levels, the Akt axis is one of the key disregulated pathways, although the molecular events are not completely understood. The aim of this review is to describe and discuss the clinical relevance of the recent advances dissecting autophagy and its signalling pathway in DMD. The picture might pave the way for the development of interventions that are able to boost muscle growth and/or prevent muscle wasting. © 2014 De_palma, Perrotta, Pellegrino, Clementi and Cervia.

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