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Your search keyword '"Diego Scheggia"' showing total 2 results
Start Over Author "Diego Scheggia" Publisher nature publishing group
2 results on '"Diego Scheggia"'

1. The epistatic interaction between the dopamine D3 receptor and dysbindin-1 modulates higher-order cognitive functions in mice and humans

Author

Mariangela Chisari, Federica Geraci, Salvatore Salomone, Francesca Managò, Gian Marco Leggio, Valentina Ferretti, M.A. De Luca, Francesco Papaleo, Filippo Drago, Céline Devroye, Daniele Mauro, Maria Angela Sortino, Sebastiano Alfio Torrisi, Claudio Bucolo, Lara Costa, Rosa Mastrogiacomo, Maddalena Mereu, Giovanni Giurdanella, Marco Nigro, Nicholas Pintori, Diego Scheggia, and Lucia Ciranna

Subjects
0301 basic medicine, Striatum, Biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Mice, 0302 clinical medicine, Cognition, Dopamine receptor D3, Dopamine receptor D2, medicine, Animals, Humans, Prefrontal cortex, Receptor, Molecular Biology, Positive and Negative Syndrome Scale, Receptors, Dopamine D2, Dysbindin, Receptors, Dopamine D3, medicine.disease, Psychiatry and Mental health, 030104 developmental biology, Schizophrenia, Neuroscience, 030217 neurology & neurosurgery
Abstract

The dopamine D2 and D3 receptors are implicated in schizophrenia and its pharmacological treatments. These receptors undergo intracellular trafficking processes that are modulated by dysbindin-1 (Dys). Indeed, Dys variants alter cognitive responses to antipsychotic drugs through D2-mediated mechanisms. However, the mechanism by which Dys might selectively interfere with the D3 receptor subtype is unknown. Here, we revealed an interaction between functional genetic variants altering Dys and D3. Specifically, both in patients with schizophrenia and in genetically modified mice, concomitant reduction in D3 and Dys functionality was associated with improved executive and working memory abilities. This D3/Dys interaction produced a D2/D3 imbalance favoring increased D2 signaling in the prefrontal cortex (PFC) but not in the striatum. No epistatic effects on the clinical positive and negative syndrome scale (PANSS) scores were evident, while only marginal effects on sensorimotor gating, locomotor functions, and social behavior were observed in mice. This genetic interaction between D3 and Dys suggests the D2/D3 imbalance in the PFC as a target for patient stratification and procognitive treatments in schizophrenia.

Published
2019

2. Remote memories are enhanced by COMT activity through dysregulation of the endocannabinoid system in the prefrontal cortex

Author

Giulia Margiani, Valentina Ferretti, Daniele Piomelli, Gabriella Contarini, Natalia Realini, M.A. De Luca, Tiziana Rubino, Daniela Parolaro, Diego Scheggia, Erica Zamberletti, Francesca Managò, Maddalena Mereu, Francesco Papaleo, and Roberto Brunoro

Subjects
Male, 0301 basic medicine, Memory, Long-Term, Cannabinoid receptor, Genotype, Dopamine, Prefrontal Cortex, Hippocampus, Mice, Transgenic, Animals, Catechol O-Methyltransferase, Cognition, Endocannabinoids, Female, Humans, Memory, Mice, Polymorphism, Genetic, Striatum, behavioral disciplines and activities, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Molecular Biology, Psychiatry and Mental Health, mental disorders, medicine, Prefrontal cortex, Recall, fungi, Executive functions, Endocannabinoid system, Psychiatry and Mental health, 030104 developmental biology, nervous system, Psychology, Neuroscience, 030217 neurology & neurosurgery, medicine.drug
Abstract

The prefrontal cortex (PFC) is a crucial hub for the flexible modulation of recent memories (executive functions) as well as for the stable organization of remote memories. Dopamine in the PFC is implicated in both these processes and genetic variants affecting its neurotransmission might control the unique balance between cognitive stability and flexibility present in each individual. Functional genetic variants in the catechol-O-methyltransferase (COMT) gene result in a different catabolism of dopamine in the PFC. However, despite the established role played by COMT genetic variation in executive functions, its impact on remote memory formation and recall is still poorly explored. Here we report that transgenic mice overexpressing the human COMT-Val gene (COMT-Val-tg) present exaggerated remote memories (>50 days) while having unaltered recent memories (

Published
2018

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