Date of Award

2018

Document Type

Dissertation/Thesis

Submission Date

October 2026

Thesis/Dissertation Advisor [Chair]

Earles, Julie L.

Abstract

Macrocephaly is a well-replicated phenotype in a subset of individuals with autism spectrum disorder (ASD). Heterozygous mutation in PTEN, which encode a negative regulator of the PI3K-mTR signaling pathway, causes the macrocephaly/autism syndrome. Mice with germline heterozygous Pten deletion (Pten+/-) exhibit both brain overgrowth and social behavioral deficits. Here, we showed that reduction of Igf-1 receptor (Igf-1r), which is an upstream receptor of PI3K-mTOR pathway, in Pten+/- mice rescues the neuronal overgrowth of cortical layer V neurons, which is associated with social behavior deficits shown in the Pten+/- mice. These are promising results shows that a pharmacological agent, one that blocks Igf1r, could recover the damage done by the Pten mutation. However, the pathway being targeted is a cellular pathway within the brain and any potential pharmacological agent must be able to cross the blood brain barrier, and must alter the pathway within the brain and not influence other pathways within the system.

Comments

Includes bibliography.

Extent

32 p.

Identifier

FAUHT00026

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