Claudio d'addario

Università degli Studi di Teramo | UNITE · Faculty of Bioscience

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 per...

Background: Prenatal ethanol exposure (PEE) induces heightened ethanol intake at adolescence in preclinical studies. Ethanol intake alters the absorption of folate, a methyl-group donor critical for numerous cellular functions. The prenatal administration of folate is, therefore, a promising approach to reduce the effects of PEE. Objectives: Experi...

Recurrent Binge Eating (BE) episodes characterize several eating disorders. Here, we attempted to reassemble a condition closer to BE disorder, and we analyzed whether recurrent episodes might evoke molecular alterations in the hypothalamus of rats. The hypothalamus is a brain region which is sensitive to stress and relevant in motivated behaviors,...

Psychopathological symptoms such as depression/anxiety vs. attention or aggression problems, in children, have been associated to altered expression of the DAT1/SLC6A3 gene. Inheriting specific 9- or 10-repeat VNTR alleles could modify the pattern of methylation in the CpGs islands at the 5’-UTR of the DAT1 gene. Through accurate recruitment at pri...

DNA methylation pattern could be considered a biomarker to be exploited for the study and management of several human diseases. In this chapter, detailed protocols are provided for two experimental approaches used for quantitative methylation analysis of bisulfite converted DNA: methylation-specific PCR (MSP) and pyrosequencing.Key wordsDNA methyla...

Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), a major development in PCR technology, is a powerful and sensitive gene analysis technique that has revolutionized the field of gene expression assays. In this chapter, we describe in detail RNA extraction, reverse transcription (RT), and relative quantification of ge...

In this chapter, we will describe the bioinformatic tools that allow verifying the presence of CpG islands in a gene promoter region. We will also describe the tools needed to identify consensus motifs for specific transcription factors, focusing on the study of rat type-1 cannabinoid receptor gene (R_Cnr1) as a case study.Key wordsGenome browsersI...

Objective: Limited studies have investigated cannabis use in patients with obsessive-compulsive disorder (OCD), despite its widespread use by patients with psychiatric illnesses. The aim of this study was to assess the frequency, correlates, and clinical impact of cannabis use in an Italian sample of patients with OCD. Methods: Seventy consecuti...

Although the etiopathogenesis of mental disorders is not fully understood, accumulating evidence support that clinical symptomatology cannot be assigned to a single gene mutation, but it involves several genetic factors. More specifically, a tight association between genes and environmental risk factors, which could be mediated by epigenetic mechan...

Compulsivity is defined as an unstoppable tendency towards repetitive and habitual actions, which are reiterated despite negative consequences. Polydipsia is induced preclinically by intermittent reward leading rodents to ingest large amounts of fluids. We focused on the role of dopamine transporter (DAT) and inheritance factors in compulsive behav...

Nowadays, the use of social networks (SNs) is pervasive and ubiquitous. Among other things, SNs have become a key resource for establishing and maintaining personal relationships, as further demonstrated by the emergence of the pandemic. However, easy access to SNs may be a source of addictive behaviour, especially among the younger population. The...

Background Obsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with env...

Individual differences in temporal and probabilistic discounting are associated with a wide range of life outcomes in literature. Traditional approaches have focused on impulsiveness and cognitive control skills, on goal-oriented personality traits as well as on the psychological perception of time. More recently, literature started to consider the...

In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of Sprague-Dawley rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produces long-lasting behavioral alterations such as social withdrawal and cognitive impairment in adulthood, mimicking a schizophrenia-like phenotype. These...

Background Brain-Derived Neurotrophic Factor (BDNF) is a promising candidate biomarker in both the development and aetiology of different neuropsychiatric conditions, including obsessive-compulsive disorder (OCD). Most of the studies in the field have been carried out in blood cells, including peripheral blood mononucleated cells (PBMCs), although...

Canine atopic dermatitis (AD) is a multifactorial allergic disease associated with immune and abnormal skin barrier dysfunction and it is one of the primary causes of pruritus. Using a novel in vitro model of AD, here we tried to revert the alteration of transcriptional regulation of AD canine key genes testing a nutraceutical mixture containing fl...

Stress vulnerability is a critical factor for the development of trauma‐related disorders, however its biological underpinnings are not clear. We demonstrated that dysfunctions in the X‐linked epigenetic factor methyl‐CpG binding protein 2 (MeCP2) provide trauma vulnerability in male mice. Given the prominent role of sex in stress outcomes, we expl...

Accumulating research addressed epigenetic modifications and their role on behavioral phenotypes. We recently proposed to study methylation dynamics of two CpG motifs within the 5’-UTR of dopamine transporter (DAT) gene. Starting from a normative population sample of young adults, we selected three sub-groups based on their prevalent symptoms: subj...

Rationale Serotonin (5-HT) plays an important role in the organization of the central nervous system and in the development of social interaction deficits and psychiatric disorders, including anxiety, depression, and addiction disorders. Notably, disruption of the 5-HT system during sensitive periods of development exerts long-term consequences, in...

Different neuromodulatory systems are involved in long-term energy balance and body weight and, among these, evidence shows that the endocannabinoid system, in particular the activation of type-1 cannabinoid receptor, plays a key role. We here review current literature focusing on the role of the gene encoding type-1 cannabinoid receptors in the CN...

Perinatal exposure to Δ9-tetrahydrocannabinol (THC) affects brain development and might increase the incidence of psychopathology later in life, which seems to be related to a dysregulation of endocannabinoid and/or dopaminergic systems. We here evaluated the transcriptional regulation of the genes encoding for the cannabinoid CB1 receptor (Cnr1) a...

Parkinson's disease (PD) is a neuro-degenerative disorder affecting the striatal motor system, caused by the loss of neuronal cells in the mid-brain, where reduced amounts of dopamine do cause involuntary movements and others symptoms. Alterations of methylome have been reported in PD epigenomic studies, and also human dopamine transporter gene (DA...

Obsessive-Compulsive Disorder (OCD) is a prevalent and severe clinical condition whose hallmarks are excessive, unwanted thoughts (obsessions) and repetitive behaviors (compulsions). The onset of symptoms generally occurs during pre-adult life and typically affects subjects in different aspects of their life's, compromising social and professional...

Internet influences our communication, social and work interactions, entertainment, and many other aspects of life. Even if the original purpose was to simplify our lives, an excessive and/or maladaptive use of it may have negative consequences. The dopamine transporter (DAT1) gene was studied in relation to addictions, including excessive use of t...

[This corrects the article DOI: 10.1155/2014/169203.].

Anxiety disorders are prevalent and highly disabling mental disorders. In recent years, intensive efforts focused on the search for potential neuroimaging, genetic, and peripheral biomarkers in order to better understand the pathophysiology of these disorders, support their diagnosis, and characterize the treatment response. Of note, peripheral blo...

Background DNA methylation plays a relevant role in the regulation of gene transcription, but currently the exact quantification of transcription factors binding to methylated DNA is not being determined. The binding of the transcription factor cAMP response element-binding protein-1 to its cognate CpG containing motif is known to be impaired upon...

Objectives The involvement of epigenetics mechanisms in the transcriptional regulation of key genes has been investigated in the initiation and progression of neurodegenerative disorders, including Parkinson’s disease (PD). Among others, we here focused the attention on the dopamine transporter (DAT) gene playing a critical role in maintaining the...

Attention Deficit / Hyperactivity Disorder (ADHD) is the most common neuro-developmental alteration in childhood. To date, its diagnosis is exclusively clinical, however recent studies focused on searching for objective biomarkers. We recently reported a selective alteration of DNA methylation in the 5′-UTR of dopamine transporter (DAT1) gene, in a...

Frontotemporal dementia (FTD) includes a group of neurocognitive syndromes, clinically characterized by altered behaviors, impairment of language proficiency, and altered executive functioning. FTD is one of the most frequently observed forms of dementia in the elderly population and the most common in presenile age. As for other subtypes of dement...

Objective Both environmental and genetic factors are known to contribute to the development of anorexia nervosa (AN), but the exact etiology remains poorly understood. Herein, we studied the transcriptional regulation of the endocannabinoid system, an interesting target for body weight maintenance and the control of food intake and energy balance....

Historically, the roots of alcoholism have been linked to either environment or heredity. However, the interaction between these factors is still largely unexplored. The evidence supports a link between alcohol consumption and the endogenous opioid system. We here studied the opioid genes expression in male and female Wistar rats derived from a sho...

Gestational methylazoxymethanol acetate (MAM) treatment produces offspring with adult phenotype relevant to schizophrenia, including positive- and negative-like symptoms, cognitive deficits, dopaminergic dysfunction, structural and functional abnormalities. Here we show that adult rats prenatally treated with MAM at gestational day 17 display signi...

Background: Social Anxiety Disorder (SAD) is a relatively frequent psychiatric disorder, with a lifetime prevalence of about 4% [1], which usually starts in adolescence [2]. As in the case of other mental disorders, [3] SAD has also been linked to academic impairment and school drop-out [4,5], but this previous research has a number of methodologic...

Ethanol use is widespread in adolescents, yet only some transition to problematic drinking. It is important to understand why the risk for problematic drinking varies across sub-groups of adolescents. This study reports a short-term selection program to generate Wistar rat lines (high and low adolescent ethanol drinking, ADHI and ADLO lines, respec...

Background: The brain-derived neurotrophic factor (BDNF) rs6265 (Val66Met) Met allele is associated with early onset (≤ 19 years old) bipolar disorder (BD). Val66Met (G196A) creates a CpG site when the Val/G allele is present. We sought to study the methylation of the BDNF promoter and its interaction with Val66Met genotype in BD. Methods: Sex/a...

Patients suffering from autoimmune diseases are more susceptible to mental disorders yet, the existence of specific cellular and molecular mechanisms behind the co-morbidity of these pathologies is far from being fully elucidated. By generating transgenic mice overexpressing Annexin-A1 exclusively in T cells to study its impact in models of autoimm...

Flavonoids have been shown to modulate GLP-1 in obesity. GLP-1 induces some of its effects through the intestinal GLP-1 receptor (GLP-1R), though no data exist on how flavonoids affect this receptor. Here, we examine how a dose of grape seed proanthocyanidin extract (GSPE) with anti-obesity activity affects intestinal GLP-1R and analyze whether epi...

Prenatal ethanol exposure (PEE) promotes ethanol consumption in the adolescent offspring accompanied by the transcriptional regulation of kappa opioid receptor (KOR) system genes. This study analysed if environmental enrichment (EE, from gestational day 20 to postnatal day 26) exerts protective effects upon PEE-modulation of gene expression, ethano...

Patients suffering from autoimmune diseases are more susceptible to mental disorders yet, the existence of specific cellular and molecular mechanisms behind the co-morbidity of these pathologies is far from being fully elucidated. By generating transgenic mice overexpressing Annexin-A1 exclusively in T cells to study its impact in models of autoimm...

Parental psychopathological risk is considered as one of the most crucial features associated with epigenetic modifications in offspring, which in turn are thought to be related to their emotional/behavioral profiles. The dopamine active transporter (DAT) gene is suggested to play a significant role in affective/behavioral regulation. On the basis...

Adenosine A2A receptors (A2ARs) have attracted considerable attention as an important molecular target for the design of Parkinson’s disease (PD) therapeutic compounds. Here, we studied the transcriptional regulation of the A2AR gene in human peripheral blood mononuclear cells (PBMCs) obtained from PD patients and in the striatum of the well-valida...

5-lipoxygenase (5-LOX) is a non-heme iron-containing dioxygenase expressed in immune cells that catalyzes the two initial steps in the biosynthesis of leukotrienes. It is well known that 5-LOX activation in innate immunity cells is related to different iron-associated pro-inflammatory disorders, including cancer, neurodegenerative diseases, and ath...

Among endogenous signaling networks involved in both rewarding and homeostatic mechanisms of obesity, a relevant role is played by the endocannabinoid (ECS) and the opioid (EOS) systems. We here studied the transcriptional regulation of ECS and EOS genes in the hypothalamus of Diet-induced obesity rats, a preclinical model of obesity, as well as in...

Background: Pharmacological treatment approaches for eating disorders, such as binge eating disorder and bulimia nervosa, are currently limited. Methods and aims: Using a well-characterized animal model of binge eating, we investigated the epigenetic regulation of the A2A Adenosine Receptor (A2AAR) and dopaminergic D2 receptor (D2R) genes. Resu...

Obsessive-compulsive disorder (OCD) is a clinically heterogeneous neuropsychiatric condition associated with profound disability, whose susceptibility, stemming from genetic and environmental factors that intersect with each other, is still under investigation. In this perspective, we sought to explore the transcriptional regulation of Brain Derive...

Objective Binge‐eating episodes are recurrent and are defining features of several eating disorders. Thus binge‐eating episodes might influence eating disorder development of which exact underlying mechanisms are still largely unknown. Methods Here we focused on the transcriptional regulation of the endocannabinoid system, a potent regulator of fe...

In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produced long-lasting behavioral alterations such as social withdrawal and cognitive impairment in the social interaction test and in the novel object recognition test, resp...

In the DSM-5 a new "tic-related" specifier for obsessive compulsive disorder (OCD) has been introduced, highlighting the importance of an accurate characterization of patients suffering from obsessive-compulsive tic-related disorder ("OCTD"). In order to characterize OCTD from a socio-demographic and clinical perspective, the present multicenter st...

Alcohol exposure and stressful events in life can induce long-lasting changes in physiology, behavior and gene expression patterns, eventually facilitating the development of psychiatric diseases like alcohol use disorders (AUD). Epigenetic mechanisms have been recently proposed to play a role in the cellular actions of alcohol via chromatin remode...

Animal models have suggested that prenatal ethanol exposure (PEE) alters the κ opioid receptor system. The present study investigated the brain expression of dynorphin and nociceptin/orphanin FQ related genes and assessed anxiety-like behavior in the light-dark box (LDB), shelter-seeking and risk-taking behaviors in the concentric square field (CSF...

In view of the need for easily accessible biomarkers, we evaluated in ADHD children the epigenetic status of the 5'-untranslated region (UTR) in the SLC6A3 gene, coding for human dopamine transporter (DAT). We analysed buccal swabs and sera from 30 children who met DSM-IV-TR criteria for ADHD, assigned to treatment according to severity. Methylatio...

Background The effect of gene polymorphisms and promoter methylation, associated with maladaptive developmental outcomes, vary depending on environmental factors (e.g., parental psychopathology). Most studies have focused on 0- to 5-year-old children, adolescents, or adults, whereas there is dearth of research on school-age youths and pre-adolescen...

Bipolar Disorder (BD) is a prevalent and disabling condition, determined by gene-environment interactions, possibly mediated by epigenetic mechanisms. The present study aimed at investigating the transcriptional regulation of BD selected target genes by DNA methylation in peripheral blood mononuclear cells of patients with a DSM-5 diagnosis of type...

Dynorphins are critically involved in the development, maintenance and relapse of alcoholism. Alcohol-induced changes in the prodynorphin gene expression may be influenced by both gene polymorphisms and epigenetic modifications. The present study of human alcoholics aims to evaluate DNA methylation patterns in the prodynorphin gene (PDYN) promoter...

Compelling evidence supports the involvement of the endocannabinoid system (ECS) in psychosis vulnerability. We here evaluated the transcriptional regulation of ECS components in human peripheral blood mononuclear cells (PBMCs) obtained from subjects suffering from bipolar disorder, major depressive disorder and schizophrenia, focusing in particula...

Alcohol exposure alters factors that modify gene expression in both animals and humans, and a pivotal role in these processes is played by epigenetic mechanisms, a set of posttranslational modifications that regulate gene expression, without causing variation in DNA sequence. The epigenetic machinery includes DNA methylation, histone modifications,...

Target genes in Alzheimer’s disease (AD) have been identified. In monozygotic twins discordant for AD we analysed the expression of selected genes, and their possible regulation by epigenetic mechanisms in peripheral blood mononuclear cells, possibly useful to discover biomarkers. Amyloid precursor protein, sirtuin 1 and peptidyl prolyl isomerase 1...