title: Treating the Synapse in Major Psychiatric Disorders: The Role of Postsynaptic Density Network in Dopamine-Glutamate Interplay and Psychopharmacologic Drugs Molecular Actions.
abstract: Dopamine-glutamate interplay dysfunctions have been suggested as pathophysiological key determinants of major psychotic disorders, above all schizophrenia and mood disorders. For the most part, synaptic interactions between dopamine and glutamate signaling pathways take part in the postsynaptic density, a specialized ultrastructure localized under the membrane of glutamatergic excitatory synapses. Multiple proteins, with the role of adaptors, regulators, effectors, and scaffolds compose the postsynaptic density network. They form structural and functional crossroads where multiple signals, starting at membrane receptors, are received, elaborated, integrated, and routed to appropriate nuclear targets. Moreover, transductional pathways belonging to different receptors may be functionally interconnected through postsynaptic density molecules. Several studies have demonstrated that psychopharmacologic drugs may differentially affect the expression and function of postsynaptic genes and proteins, depending upon the peculiar receptor profile of each compound. Thus, through postsynaptic network modulation, these drugs may induce dopamine-glutamate synaptic remodeling, which is at the basis of their long-term physiologic effects. In this review, we will discuss the role of postsynaptic proteins in dopamine-glutamate signals integration, as well as the peculiar impact of different psychotropic drugs used in clinical practice on postsynaptic remodeling, thereby trying to point out the possible future molecular targets of "synapse-based" psychiatric therapeutic strategies.
authors.affiliation: NHS, Department of Mental Health ASL Teramo, Psychiatric Service of Diagnosis and Treatment, Hospital "Maria SS dello Splendore", 641021 Giulianova, Italy. carmine.tomasetti@unina.it.|Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatogical Sciences, University of Naples "Federico II", 80131 Napoli, Italy. carmine.tomasetti@unina.it.|Polyedra Research Group, 64100 Teramo, Italy. carmine.tomasetti@unina.it.
authors.forename: Carmine
authors.initials: C
authors.lastname: Tomasetti
authors.affiliation: Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatogical Sciences, University of Naples "Federico II", 80131 Napoli, Italy. felix_ias@hotmail.com.|Polyedra Research Group, 64100 Teramo, Italy. felix_ias@hotmail.com.
authors.forename: Felice
authors.initials: F
authors.lastname: Iasevoli
authors.affiliation: Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatogical Sciences, University of Naples "Federico II", 80131 Napoli, Italy. lisabuonaguro@tin.it.|Polyedra Research Group, 64100 Teramo, Italy. lisabuonaguro@tin.it.
authors.forename: Elisabetta Filomena
authors.initials: EF
authors.lastname: Buonaguro
authors.affiliation: Polyedra Research Group, 64100 Teramo, Italy. dodebera@alice.it.|NHS, Department of Mental Health ASL Teramo, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", 64100 Teramo, Italy. dodebera@alice.it.|Department of Neuroscience and Imaging, University "G. d'Annunzio", 66100 Chieti, Italy. dodebera@alice.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: De Berardis
authors.affiliation: Polyedra Research Group, 64100 Teramo, Italy. dott.fornaro@gmail.com.|New York State Psychiatric Institute, Columbia University, New York, NY 10027, USA. dott.fornaro@gmail.com.
authors.forename: Michele
authors.initials: M
authors.lastname: Fornaro
authors.affiliation: Polyedra Research Group, 64100 Teramo, Italy. annastasia.fiengo@gmail.com.
authors.forename: Annastasia Lucia Carmela
authors.initials: AL
authors.lastname: Fiengo
authors.affiliation: Polyedra Research Group, 64100 Teramo, Italy. giovanni.martinotti@gmail.com.|Department of Neuroscience and Imaging, University "G. d'Annunzio", 66100 Chieti, Italy. giovanni.martinotti@gmail.com.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinotti
authors.affiliation: Polyedra Research Group, 64100 Teramo, Italy. laura.orsolini@hotmail.it.|Casa di Cura Villa San Giuseppe, 63100 Ascoli Piceno, Italy. laura.orsolini@hotmail.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Orsolini
authors.affiliation: Polyedra Research Group, 64100 Teramo, Italy. alessandrovalchera@gmail.com.|Casa di Cura Villa San Giuseppe, 63100 Ascoli Piceno, Italy. alessandrovalchera@gmail.com.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Valchera
authors.affiliation: Department of Neuroscience and Imaging, University "G. d'Annunzio", 66100 Chieti, Italy. digiannantonio@unich.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Giannantonio
authors.affiliation: Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatogical Sciences, University of Naples "Federico II", 80131 Napoli, Italy. adebarto@unina.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: de Bartolomeis
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008954:Models, Biological; D057907:Post-Synaptic Density / Q000378:metabolism*; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D047908:Intracellular Signaling Peptides and Proteins; D018698:Glutamic Acid; D004298:Dopamine
keywords: Homer; bipolar disorder; gene expression; postsynaptic density (PSD); schizophrenia; transductional pathways