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 Alberini

Research output: Contribution to journalArticle

Abstract

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+ Itpr3tf/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
Volume38
Issue number4
DOIs
StatePublished - Jan 24 2018

Fingerprint

Insulin-Like Growth Factor II
Autistic Disorder
Phenotype
Interpersonal Relations
Nootropic Agents
IGF Type 2 Receptor
Developmental Disabilities
IGF Type 1 Receptor
AMP-Activated Protein Kinases
Executive Function
Synapses
Cognition
Autism Spectrum Disorder
Peptides
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Insulin-like growth factor II targets the mTOR pathway to reverse autism-like phenotypes in mice. / Steinmetz, Adam B.; Stern, Sarah A.; Kohtz, Amy S.; Descalzi, Giannina; Alberini, Cristina.

In: Journal of Neuroscience, Vol. 38, No. 4, 24.01.2018, p. 1015-1029.

Research output: Contribution to journalArticle

Steinmetz, Adam B. ; Stern, Sarah A. ; Kohtz, Amy S. ; Descalzi, Giannina ; Alberini, Cristina. / Insulin-like growth factor II targets the mTOR pathway to reverse autism-like phenotypes in mice. In: Journal of Neuroscience. 2018 ; Vol. 38, No. 4. pp. 1015-1029.
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