Oxytocin improves behavioral and electrophysiological deficits in a novel Shank3-deficient rat

Hala Harony-Nicolas, Maya Kay, Johann du Hoffmann, Matthew E. Klein, Ozlem Bozdagi-Gunal, Mohammed Riad, Nikolaos P. Daskalakis, Sankalp Sonar, Pablo E. Castillo, Patrick R. Hof, Matthew L. Shapiro, Mark G. Baxter, Shlomo Wagner, Joseph D. Buxbaum

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Mutations in the synaptic gene SHANK3 lead 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 a Shank3-deficient rat model of PMS, with a genetic alteration similar to a human SHANK3 mutation. We show that Shank3-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.

Original languageEnglish (US)
Article numbere18904
JournaleLife
Volume6
DOIs
StatePublished - Jan 31 2017

Fingerprint

Oxytocin
Rats
Plasticity
Genes
Intellectual Disability
Data storage equipment
Mutation
Neuronal Plasticity
Neurobiology
Prefrontal Cortex
Therapeutics
Telomeric 22q13 Monosomy Syndrome
Pharmacology
Autism Spectrum Disorder

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Harony-Nicolas, H., Kay, M., du Hoffmann, J., Klein, M. E., Bozdagi-Gunal, O., Riad, M., ... Buxbaum, J. D. (2017). Oxytocin improves behavioral and electrophysiological deficits in a novel Shank3-deficient rat. eLife, 6, [e18904]. https://doi.org/10.7554/eLife.18904
Harony-Nicolas, Hala ; Kay, Maya ; du Hoffmann, Johann ; Klein, Matthew E. ; Bozdagi-Gunal, Ozlem ; Riad, Mohammed ; Daskalakis, Nikolaos P. ; Sonar, Sankalp ; Castillo, Pablo E. ; Hof, Patrick R. ; Shapiro, Matthew L. ; Baxter, Mark G. ; Wagner, Shlomo ; Buxbaum, Joseph D. / Oxytocin improves behavioral and electrophysiological deficits in a novel Shank3-deficient rat. In: eLife. 2017 ; Vol. 6.
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abstract = "Mutations in the synaptic gene SHANK3 lead 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 a Shank3-deficient rat model of PMS, with a genetic alteration similar to a human SHANK3 mutation. We show that Shank3-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.",
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Harony-Nicolas, H, Kay, M, du Hoffmann, J, Klein, ME, Bozdagi-Gunal, O, Riad, M, Daskalakis, NP, Sonar, S, Castillo, PE, Hof, PR, Shapiro, ML, Baxter, MG, Wagner, S & Buxbaum, JD 2017, 'Oxytocin improves behavioral and electrophysiological deficits in a novel Shank3-deficient rat', eLife, vol. 6, e18904. https://doi.org/10.7554/eLife.18904

Oxytocin improves behavioral and electrophysiological deficits in a novel Shank3-deficient rat. / Harony-Nicolas, Hala; Kay, Maya; du Hoffmann, Johann; Klein, Matthew E.; Bozdagi-Gunal, Ozlem; Riad, Mohammed; Daskalakis, Nikolaos P.; Sonar, Sankalp; Castillo, Pablo E.; Hof, Patrick R.; Shapiro, Matthew L.; Baxter, Mark G.; Wagner, Shlomo; Buxbaum, Joseph D.

In: eLife, Vol. 6, e18904, 31.01.2017.

Research output: Contribution to journalArticle

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AU - Harony-Nicolas, Hala

AU - Kay, Maya

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AU - Bozdagi-Gunal, Ozlem

AU - Riad, Mohammed

AU - Daskalakis, Nikolaos P.

AU - Sonar, Sankalp

AU - Castillo, Pablo E.

AU - Hof, Patrick R.

AU - Shapiro, Matthew L.

AU - Baxter, Mark G.

AU - Wagner, Shlomo

AU - Buxbaum, Joseph D.

PY - 2017/1/31

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