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Marco bortolato

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https://www.readbyqxmd.com/read/27889491/pramipexole-enhances-disadvantageous-decision-making-lack-of-relation-to-changes-in-phasic-dopamine-release
#1
Romina Pes, Sean C Godar, Andrew T Fox, Lauren M Burgeno, Hunter J Strathman, David P Jarmolowicz, Paola Devoto, Beth Levant, Paul E M Phillips, Stephen C Fowler, Marco Bortolato
Pramipexole (PPX) is a high-affinity D2-like dopamine receptor agonist, used in the treatment of Parkinson's disease (PD) and restless leg syndrome. Recent evidence indicates that PPX increases the risk of problem gambling and impulse-control disorders in vulnerable patients. Although the molecular bases of these complications remain unclear, several authors have theorized that PPX may increase risk propensity by activating presynaptic dopamine receptors in the mesolimbic system, resulting in the reduction of dopamine release in the nucleus accumbens (NAcc)...
November 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27750143/exploring-the-neural-mechanisms-of-finasteride-a-proteomic-analysis-in-the-nucleus-accumbens
#2
Alessio Soggiu, Cristian Piras, Viviana Greco, Paola Devoto, Andrea Urbani, Luigino Calzetta, Marco Bortolato, Paola Roncada
The enzyme 5α-reductase (5αR) catalyzes the conversion of progesterone and testosterone into neuroactive steroids implicated in a wide array of behavioral functions. The prototypical 5αR inhibitor, finasteride (FIN), is clinically approved for the treatment of androgenic alopecia and benign prostatic hyperplasia. Recent evidence has shown that FIN, albeit generally well tolerated, can induce untoward psychological effects in a subset of patients; furthermore, this drug may have therapeutic efficacy for a number of different neuropsychiatric conditions, ranging from Tourette syndrome to schizophrenia...
October 6, 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/27458023/manic-symptom-severity-correlates-with-comt-activity-in-the-striatum-a-post-mortem-study
#3
Marco Bortolato, Consuelo Walss-Bass, Peter M Thompson, Jackob Moskovitz
OBJECTIVES: The enzyme catechol-O-methyltransferase (COMT), which catalyses the degradation of dopamine and norepinephrine, is posited to participate in the pathophysiology of bipolar disorder (BD) and schizophrenia. In support of this notion, rich evidence has documented that the severity of various BD and schizophrenia symptoms is moderated by rs4680, a single nucleotide polymorphism of the COMT gene featuring a valine (Val)-to-methionine (Met) substitution that results in lower catalytic activity...
July 26, 2016: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/26776902/the-role-of-monoamine-oxidase-a-in-aggression-current-translational-developments-and-future-challenges
#4
Sean C Godar, Paula J Fite, Kenneth M McFarlin, Marco Bortolato
Drawing upon the recent resurgence of biological criminology, several studies have highlighted a critical role for genetic factors in the ontogeny of antisocial and violent conduct. In particular, converging lines of evidence have documented that these maladaptive manifestations of aggression are influenced by monoamine oxidase A (MAOA), the enzyme that catalyzes the degradation of brain serotonin, norepinephrine and dopamine. The interest on the link between MAOA and aggression was originally sparked by Han Brunner's discovery of a syndrome characterized by marked antisocial behaviors in male carriers of a nonsense mutation of this gene...
August 1, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/26774529/accounting-for-the-associations-between-child-maltreatment-and-internalizing-problems-the-role-of-alexithymia
#5
Shaquanna Brown, Paula J Fite, Katie Stone, Marco Bortolato
Internalizing difficulties are one of the most widely documented consequences of child maltreatment. However, there is a need for studies delineating the factors that account for this association. Despite research showing that alexithymia is associated with both child maltreatment and internalizing problems, the role of alexithymia in the link between child maltreatment and internalizing problems has not received much attention in the literature. The current study evaluated whether a history of child maltreatment was associated with symptoms of depression, anxiety, and loneliness in emerging adulthood, and whether alexithymia partially accounted for these associations...
February 2016: Child Abuse & Neglect
https://www.readbyqxmd.com/read/26296373/adverse-effects-of-5%C3%AE-reductase-inhibitors-what-do-we-know-don-t-know-and-need-to-know
#6
REVIEW
Abdulmaged M Traish, Roberto Cosimo Melcangi, Marco Bortolato, Luis M Garcia-Segura, Michael Zitzmann
Steroids are important physiological orchestrators of endocrine as well as peripheral and central nervous system functions. One of the key processes for regulation of these molecules lies in their enzymatic processing by a family of 5α-reductase (5α-Rs) isozymes. By catalyzing a key rate-limiting step in steroidogenesis, this family of enzymes exerts a crucial role not only in the physiological control but also in pathological events. Indeed, both 5α-R inhibition and supplementation of 5α-reduced metabolites are currently used or have been proposed as therapeutic strategies for a wide array of pathological conditions...
September 2015: Reviews in Endocrine & Metabolic Disorders
https://www.readbyqxmd.com/read/26171666/the-d1ct-7-mouse-model-of-tourette-syndrome-displays-sensorimotor-gating-deficits-in-response-to-spatial-confinement
#7
Sean C Godar, Laura J Mosher, Hunter J Strathman, Andrea M Gochi, Cori M Jones, Stephen C Fowler, Marco Bortolato
BACKGROUND AND PURPOSE: The D1CT-7 mouse is one of the best known animal models of Tourette syndrome (TS), featuring spontaneous tic-like behaviours sensitive to standard TS therapies; these characteristics ensure a high face and predictive validity of this model, yet its construct validity remains elusive. To address this issue, we studied the responses of D1CT-7 mice to two critical components of TS pathophysiology: the exacerbation of tic-like behaviours in response to stress and the presence of sensorimotor gating deficits, which are thought to reflect the perceptual alterations causing the tics...
July 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/26101934/selective-activation-of-d1-dopamine-receptors-impairs-sensorimotor-gating-in-long-evans-rats
#8
Laura J Mosher, Roberto Frau, Alessandra Pardu, Romina Pes, Paola Devoto, Marco Bortolato
BACKGROUND AND PURPOSE: Sensorimotor gating is a perceptual process aimed at filtering out irrelevant information. In humans and animal models, this function can be operationally measured through the prepulse inhibition (PPI) of the acoustic startle reflex. Notably, PPI deficits are associated with numerous neuropsychiatric conditions characterized by gating disturbances, including schizophrenia and Tourette syndrome. Ample evidence has shown that dopamine plays a key role in PPI regulation and, in particular, rodent studies indicate that this neurotransmitter modulates PPI through D1 and D2 dopamine receptors...
July 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/25999042/targeting-neurosteroid-synthesis-as-a-therapy-for-schizophrenia-related-alterations-induced-by-early-psychosocial-stress
#9
Roberto Frau, Federico Abbiati, Valentina Bini, Alberto Casti, Donatella Caruso, Paola Devoto, Marco Bortolato
BACKGROUND: Cogent evidence has shown that schizophrenia vulnerability is enhanced by psychosocial stress in adolescence, yet the underpinnings of this phenomenon remain elusive. One of the animal models that best capture the relationship between juvenile stress and schizophrenia is isolation rearing (IR). This manipulation, which consists in subjecting rats to social isolation from weaning through adulthood, results in neurobehavioral alterations akin to those observed in schizophrenia patients...
November 2015: Schizophrenia Research
https://www.readbyqxmd.com/read/25857821/monoamine-oxidase-a-is-required-for-rapid-dendritic-remodeling-in-response-to-stress
#10
Sean C Godar, Marco Bortolato, Sarah E Richards, Felix G Li, Kevin Chen, Cara L Wellman, Jean C Shih
BACKGROUND: Acute stress triggers transient alterations in the synaptic release and metabolism of brain monoamine neurotransmitters. These rapid changes are essential to activate neuroplastic processes aimed at the appraisal of the stressor and enactment of commensurate defensive behaviors. Threat evaluation has been recently associated with the dendritic morphology of pyramidal cells in the orbitofrontal cortex (OFC) and basolateral amygdala (BLA); thus, we examined the rapid effects of restraint stress on anxiety-like behavior and dendritic morphology in the BLA and OFC of mice...
July 2015: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/25759330/paraphilias-and-paraphilic-disorders-in-parkinson-s-disease-a-systematic-review-of-the-literature
#11
REVIEW
Paolo Solla, Marco Bortolato, Antonino Cannas, Cesare Salvatore Mulas, Francesco Marrosu
Paraphilias are intense urges or behaviors involving non-normative sexual interests. The newly approved diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) have established that, although paraphilias should not be regarded as inherently pathological, they ought to be qualified as paraphilic disorders if resulting in distress, impairment, or harm to the affected individual or others. Recent evidence documents that both phenomena can emerge as relatively uncommon iatrogenic consequences in Parkinson's disease (PD) patients...
April 15, 2015: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/25244952/animal-models-of-tic-disorders-a-translational-perspective
#12
REVIEW
Sean C Godar, Laura J Mosher, Giuseppe Di Giovanni, Marco Bortolato
Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects...
December 30, 2014: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/25123446/the-re-organization-of-functional-brain-networks-in-pharmaco-resistant-epileptic-patients-who-respond-to-vns
#13
Matteo Fraschini, Matteo Demuru, Monica Puligheddu, Simona Floridia, Lorenzo Polizzi, Alberto Maleci, Marco Bortolato, Arjan Hillebrand, Francesco Marrosu
Vagal nerve stimulation (VNS) is a therapeutic add-on treatment for patients with pharmaco-resistant epilepsy. The mechanism of action is still largely unknown. Previous studies have shown that brain network topology during the inter-ictal period in epileptic patients deviates from normal configuration. In the present paper, we investigate the relationship between clinical improvement induced by VNS and alterations in brain network topology. We hypothesize that, as a consequence of the VNS add-on treatment, functional brain network architecture shifts back toward a more efficient configuration in patients responding to VNS...
September 19, 2014: Neuroscience Letters
https://www.readbyqxmd.com/read/25082653/association-of-low-activity-maoa-allelic-variants-with-violent-crime-in-incarcerated-offenders
#14
Dean A Stetler, Chad Davis, Kathryn Leavitt, Ilana Schriger, Katie Benson, Samir Bhakta, Lam Chee Wang, Cynthia Oben, Matthew Watters, Tara Haghnegahdar, Marco Bortolato
The main enzyme for serotonin degradation, monoamine oxidase (MAO) A, has recently emerged as a key biological factor in the predisposition to impulsive aggression. Male carriers of low-activity variants of the main functional polymorphism of the MAOA gene (MAOA-uVNTR) have been shown to exhibit a greater proclivity to engage in violent acts. Thus, we hypothesized that low-activity MAOA-uVNTR alleles may be associated with a higher risk for criminal violence among male offenders. To test this possibility, we analyzed the MAOA-uVNTR variants of violent (n = 49) and non-violent (n = 40) male Caucasian and African-American convicts in a correctional facility...
November 2014: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/24882701/the-aggression-and-behavioral-abnormalities-associated-with-monoamine-oxidase-a-deficiency-are-rescued-by-acute-inhibition-of-serotonin-reuptake
#15
Sean C Godar, Marco Bortolato, M Paola Castelli, Alberto Casti, Angelo Casu, Kevin Chen, M Grazia Ennas, Simone Tambaro, Jean C Shih
The termination of serotonin (5-hydroxytryptamine, 5-HT) neurotransmission is regulated by its uptake by the 5-HT transporter (5-HTT), as well as its degradation by monoamine oxidase (MAO)-A. MAO-A deficiency results in a wide set of behavioral alterations, including perseverative behaviors and social deficits. These anomalies are likely related to 5-HTergic homeostatic imbalances; however, the role of 5-HTT in these abnormalities remains unclear. To ascertain the role of 5-HTT in the behavioral anomalies associated to MAO-A deficiency, we tested the behavioral effects of its blocker fluoxetine on perseverative, social and aggressive behaviors in transgenic animals with hypomorphic or null-allele MAO-A mutations...
September 2014: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/24735585/methionine-sulfoxide-reductase-regulates-brain-catechol-o-methyl-transferase-activity
#16
Jackob Moskovitz, Consuelo Walss-Bass, Dianne A Cruz, Peter M Thompson, Marco Bortolato
Catechol-O-methyl transferase (COMT) plays a key role in the degradation of brain dopamine (DA). Specifically, low COMT activity results in higher DA levels in the prefrontal cortex (PFC), thereby reducing the vulnerability for attentional and cognitive deficits in both psychotic and healthy individuals. COMT activity is markedly reduced by a non-synonymous single-nucleotide polymorphism (SNP) that generates a valine-to-methionine substitution on the residue 108/158, by means of as-yet incompletely understood post-translational mechanisms...
October 2014: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/24703381/positive-allosteric-modulation-of-gabab-receptors-ameliorates-sensorimotor-gating-in-rodent-models
#17
Roberto Frau, Valentina Bini, Giuliano Pillolla, Pari Malherbe, Alessandra Pardu, Andrew W Thomas, Paola Devoto, Marco Bortolato
BACKGROUND: Converging evidence points to the involvement of γ-amino-butyric acid B receptors (GABABRs) in the regulation of information processing. We previously showed that GABABR agonists exhibit antipsychotic-like properties in rodent models of sensorimotor gating deficits, as measured by the prepulse inhibition (PPI) of the acoustic startle reflex. The therapeutic potential of these agents, however, is limited by their neuromuscular side effects; thus, in this study, we analyzed whether rac-BHFF, a potent GABABR-positive allosteric modulator (PAM), could counter spontaneous and pharmacologically induced PPI deficits across various rodent models...
July 2014: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/24639636/gene-sex-interactions-in-schizophrenia-focus-on-dopamine-neurotransmission
#18
REVIEW
Sean C Godar, Marco Bortolato
Schizophrenia is a severe mental disorder, with a highly complex and heterogenous clinical presentation. Our current perspectives posit that the pathogenic mechanisms of this illness lie in complex arrays of gene × environment interactions. Furthermore, several findings indicate that males have a higher susceptibility for schizophrenia, with earlier age of onset and overall poorer clinical prognosis. Based on these premises, several authors have recently begun exploring the possibility that the greater schizophrenia vulnerability in males may reflect specific gene × sex (G×S) interactions...
2014: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/24630433/juvenile-cannabinoid-treatment-induces-frontostriatal-gliogenesis-in-lewis-rats
#19
Marco Bortolato, Valentina Bini, Roberto Frau, Paola Devoto, Alessandra Pardu, Yijun Fan, Marylou V Solbrig
Cannabis abuse in adolescence is associated with a broad array of phenotypical consequences, including a higher risk for schizophrenia and other mental disturbances related to dopamine (DA) imbalances. The great variability of these sequelae likely depends on the key influence of diverse genetic vulnerability factors. Inbred rodent strains afford a highly informative tool to study the contribution of genetic determinants to the long-term effects of juvenile cannabinoid exposure. In this study, we analyzed the phenotypical impact of the synthetic cannabinoid agonist WIN 55,212-2 (WIN; 2mg/kg/day from postnatal day 35-48) in adolescent Lewis rats, an inbred strain exhibiting resistance to psychotomimetic effects of environmental manipulations...
June 2014: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/24140269/inhibition-of-17%C3%AE-hydroxylase-c17-20-lyase-reduces-gating-deficits-consequent-to-dopaminergic-activation
#20
Roberto Frau, Valentina Bini, Romina Pes, Giuliano Pillolla, Pierluigi Saba, Paola Devoto, Marco Bortolato
Cogent evidence points to the involvement of neurosteroids in the regulation of dopamine (DA) neurotransmission and signaling, yet the neurobiological bases of this link remain poorly understood. We previously showed that inhibition of 5α-reductase (5αR), a key neurosteroidogenic enzyme, attenuates the sensorimotor gating deficits induced by DA receptor activation, as measured by the prepulse inhibition (PPI) of the acoustic startle reflex. To extend these findings, the present study was aimed at the assessment of the role of other key neurosteroidogenic enzymes in PPI, such as 17α-hydroxylase/C17,20 lyase (CYP17A1), 3α- and 3β-hydroxysteroid dehydrogenase (HSD), in Sprague-Dawley rats...
January 2014: Psychoneuroendocrinology
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