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 language | English (US) |
|---|---|
| Article number | e18904 |
| Journal | eLife |
| Volume | 6 |
| DOIs | |
| State | Published - Jan 31 2017 |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)
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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 journal › Article
TY - JOUR
T1 - Oxytocin improves behavioral and electrophysiological deficits in a novel Shank3-deficient rat
AU - Harony-Nicolas, Hala
AU - Kay, Maya
AU - du Hoffmann, Johann
AU - Klein, Matthew E.
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
Y1 - 2017/1/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85011397525&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011397525&partnerID=8YFLogxK
U2 - 10.7554/eLife.18904
DO - 10.7554/eLife.18904
M3 - Article
C2 - 28139198
AN - SCOPUS:85011397525
VL - 6
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e18904
ER -