Pharmacological modulation of AMPA receptors rescues specific impairments in social behavior associated with the A350V Iqsec2 mutation

Renad Jabarin, Nina Levy, Yasmin Abergel, Joshua H. Berman, Amir Zag, Shai Netser, Andrew P. Levy, Shlomo Wagner

Research output: Contribution to journalArticlepeer-review

Abstract

In this study we tested the hypothesis that pharmacological modulation of glutamatergic neurotransmission could rescue behavioral deficits exhibited by mice carrying a specific mutation in the Iqsec2 gene. The IQSEC2 protein plays a key role in glutamatergic synapses and mutations in the IQSEC2 gene are a frequent cause of neurodevelopmental disorders. We have recently reported on the molecular pathophysiology of one such mutation A350V and demonstrated that this mutation downregulates AMPA type glutamatergic receptors (AMPAR) in A350V mice. Here we sought to identify behavioral deficits in A350V mice and hypothesized that we could rescue these deficits by PF-4778574, a positive AMPAR modulator. Using a battery of social behavioral tasks, we found that A350V Iqsec2 mice exhibit specific deficits in sex preference and emotional state preference behaviors as well as in vocalizations when encountering a female mouse. The social discrimination deficits, but not the impaired vocalization, were rescued with a single dose of PF-4778574. We conclude that social behavior deficits associated with the A350V Iqsec2 mutation may be rescued by enhancing AMPAR mediated synaptic transmission.

Original languageEnglish
Article number234
JournalTranslational Psychiatry
Volume11
Issue number1
DOIs
StatePublished - Jun 2021

Bibliographical note

Funding Information:
This study was supported by The Human Frontier Science Program (HFSP grant RGP0019/2015 for SW), the Israel Science Foundation (ISF grants #1350/ 12, 1361/17 for S.W.), by a donation by the Milgrom family for SW and by the Ministry of Science, Technology and Space of Israel (Grant #3-12068 for S.W.).

Publisher Copyright:
© 2021, The Author(s).

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

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