title: Oxytocin improves behavioral and electrophysiological deficits in a novel Shank3-deficient rat.
abstract: Mutations in the synaptic geneSHANK3lead to a neurodevelopmental disorder known as Phelan-McDermid syndrome (PMS). PMS is a relatively common monogenic and highly penetrant cause of autism spectrum disorder (ASD) and intellectual disability (ID), and frequently presents with attention deficits. The underlying neurobiology of PMS is not fully known and pharmacological treatments for core symptoms do not exist. Here, we report the production and characterization of aShank3-deficient rat model of PMS, with a genetic alteration similar to a human SHANK3 mutation. We show thatShank3-deficient rats exhibit impaired long-term social recognition memory and attention, and reduced synaptic plasticity in the hippocampal-medial prefrontal cortex pathway. These deficits were attenuated with oxytocin treatment. The effect of oxytocin on reversing non-social attention deficits is a particularly novel finding, and the results implicate an oxytocinergic contribution in this genetically defined subtype of ASD and ID, suggesting an individualized therapeutic approach for PMS.
authors.affiliation: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, United States.|Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States.
authors.forename: Hala
authors.identifier: 0000-0001-8283-9093
authors.initials: H
authors.lastname: Harony-Nicolas
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Haifa, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Kay
authors.affiliation: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, United States.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, United States.
authors.forename: Johann
authors.initials: J
authors.lastname: du Hoffmann
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, United States.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Klein
authors.affiliation: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, United States.|Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Bozdagi-Gunal
authors.affiliation: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, United States.|Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Riad
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States.
authors.forename: Nikolaos P
authors.initials: NP
authors.lastname: Daskalakis
authors.affiliation: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, United States.|Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States.
authors.forename: Sankalp
authors.initials: S
authors.lastname: Sonar
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, United States.
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Castillo
authors.affiliation: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, United States.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, United States.|Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, United States.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Hof
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, United States.|Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, United States.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Shapiro
authors.affiliation: Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, United States.|Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, United States.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Baxter
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Haifa, Israel.
authors.forename: Shlomo
authors.identifier: 0000-0002-7618-0752
authors.initials: S
authors.lastname: Wagner
authors.affiliation: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, United States.|Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, United States.|Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, United States.|Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, United States.|The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, United States.
authors.forename: Joseph D
authors.identifier: 0000-0001-8898-8313
authors.initials: JD
authors.lastname: Buxbaum
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002892:Chromosomes, Human, Pair 22; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000172:deficiency*; D010121:Oxytocin / Q000008:administration & dosage*; D017397:Prefrontal Cortex / Q000473:pathology; D051381:Rats; D012919:Social Behavior
chemical_list: D009419:Nerve Tissue Proteins; C120532:Shank3 protein, rat; D010121:Oxytocin
keywords: Phelan McDermid Syndrome; Shank3; attention; autism spectrum disorder; neuroscience; oxytocin; rat; social behavior