Insulin-like growth factor II targets the mTOR pathway to reverse autism-like phenotypes in mice

Adam B. Steinmetz, Sarah A. Stern, Amy S. Kohtz, Giannina Descalzi, Cristina M. Alberini

Research output: Contribution to journalArticlepeer-review


Autism spectrum disorder (ASD) is a developmental disability characterized by impairments in social interaction and repetitive behavior, and is also associated with cognitive deficits. There is no current treatment that can ameliorate most of the ASD symptomatology; thus, identifying novel therapies is urgently needed. We used male BTBR T + Itpr3 tf /J (BTBR) mice, a model that reproduces most of the core behavioral phenotypes of ASD, to test the effects of systemic administration of insulin-like growth factor II (IGF-II), a polypeptide that crosses the blood–brain barrier and acts as a cognitive enhancer. We show that systemic IGF-II treatments reverse the typical defects in social interaction, cognitive/executive functions, and repetitive behaviors reflective of ASD-like phenotypes. In BTBR mice, IGF-II, via IGF-II receptor, but not via IGF-I receptor, reverses the abnormal levels of the AMPK-mTOR-S6K pathway and of active translation at synapses. Thus, IGF-II may represent a novel potential therapy for ASD.

Original languageEnglish (US)
Pages (from-to)1015-1029
Number of pages15
JournalJournal of Neuroscience
Issue number4
StatePublished - Jan 24 2018


  • Autism spectrum disorder
  • Insulin-like growth factor II
  • Insulin-like growth factor II receptor
  • Memory
  • Mouse model
  • mTOR

ASJC Scopus subject areas

  • General Neuroscience


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