title: Synaptic plasticity as a therapeutic target in the treatment of autism-related single-gene disorders.
abstract: The term "Autism Spectrum" is often used to describe disorders that are currently classified as Pervasive Developmental Disorders. These disorders are typically characterized by social deficits, communication difficulties, stereotyped or repetitive behaviors and/or cognitive delays or mental retardation; sometimes they present high comorbidity rates with epilepsy. Although these diagnoses share some common features, individuals with these disorders are thought to be "on the spectrum" because of differences in severity across these domains. Recent advances in the genetics of autism spectrum disorders (ASDs) are offering new valuable insights into molecular and cellular mechanisms of pathology. Of particular interest are transgenic technologies that allowed the engineering of several mouse models mimicking different kinds of monogenic heritable forms of ASDs. These transgenic models provide excellent opportunities to explore in detail cellular and molecular mechanisms underlying disease pathology and to identify novel targets for therapeutic intervention. Increasing evidence suggests that the pathophysiological core of the murine model is primarily due to changes in normal synaptic transmission and plasticity. Here, we will extensively review the synaptic alterations across different animal models of ASDs and recapitulate the pharmacological strategies aimed at rescuing hippocampal plasticity phenotypes. We describe how pharmacological modulation of mGlu5 receptor, through the use of positive or negative allosteric modulators (depending on the specific disorder), may represent a promising therapeutic strategy for ASDs treatment.
authors: Dept. of Physiology and Pharmacology, University of Rome "Sapienza", Piazzale Aldo Moro, 5, 00185 Rome; Italy. marco.pignatelli@hotmail.it.
authors: Marco
authors: M
authors: Pignatelli
authors: Marco
authors: M
authors: Feligioni
authors: Sonia
authors: S
authors: Piccinin
authors: Gemma
authors: G
authors: Molinaro
authors: Ferdinando
authors: F
authors: Nicoletti
authors: Robert
authors: R
authors: Nisticò
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002659:Child Development Disorders, Pervasive / Q000235:genetics* / Q000628:therapy*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D009473:Neuronal Plasticity / Q000235:genetics*; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors; D013569:Synapses / Q000187:drug effects* / Q000473:pathology
chemical_list: D014150:Antipsychotic Agents; D064529:Receptor, Metabotropic Glutamate 5