# Postnatal Oxytocin Treatment and Cognitive Function in FragileX

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2023 · $52,357

## Abstract

Abstract/Summary of parent award R01HD101642
Autism Spectrum Disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder with high co-
morbidity for intellectual disability. This includes difficulties forming episodic memories that are critical for
orderly thinking and organizing future behaviors. Episodic memory deficits are thus thought to be major
contributors to cognitive difficulties associated with autism. Many of the brain changes underlying abnormalities
in ASD appear in childhood suggesting the possibility for effective therapeutic strategies targeting brain
maturation. One candidate therapeutic is the hypothalamic peptide Oxytocin (OXT). Postnatal OXT treatment
improves social behavior in animal models of ASDs and recent work indicates that OXT treatment in childhood
improves social interactions in autistic individuals. OXT acutely facilitates forms of synaptic plasticity underlying
learning, but there has been little experimental consideration of possible enduring effects of postnatal OXT
treatment on learning and no analyses of effects on episodic memory. We examined this possibility using
intranasal OXT (iOXT) treatment in the Fmr1 KO mouse model of Fragile X Syndrome (FXS), and novel
paradigms for analyses of ‘What, When and Where’ encoding. Our results show that in Fmr1 KOs iOXT
treatments during the second postnatal week (P7-13) fully rescue hippocampal field CA1 LTP, object location
memory, and object identity learning as assessed in adulthood (i.e., from 2-7 mo of age). iOXT also improved
social recognition. These findings raise the exciting possibility that a limited period of early life OXT treatment
can effect a life-long rescue of a critical element of cognitive function in ASD. They also raise questions as to
the breadth of iOXT effects on behavior and the mechanisms involved. Aim 1 studies will test if postnatal iOXT
treatment of male and female Fmr1 KOs rescues hippocampus-dependent encoding for the three major
components of episodic memory as assessed in adulthood, if effects depend on native OXT efflux. We will
further test the breadth of iOXT effects and, specifically if these treatments attenuate the cardinal behavioral
abnormalities in FXS and other ASDs (hyperlocomotion, repetitive behavior). Aim 2 will use
electrophysiological recordings, analyses of synaptic proteins and signaling, and measures of neuronal arbors
to test if iOXT treatment normalizes neurobiological processes related to encoding in hippocampus. Aim 3 will
then test the hypothesis that early life iOXT activates synaptic trophic factor receptors (EGFR, TrkB) in
hippocampus, thereby suggesting a direct route for OXT effects on maturational changes in the structure.
These studies will greatly expand our current knowledge of oxytocin actions in the young brain, including
potential roles in regulating hippocampal development and synaptic function. Moreover, the results will lay the
groundwork for designing novel, effective, and well toler...

## Key facts

- **NIH application ID:** 10842114
- **Project number:** 3R01HD101642-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Christine M Gall
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $52,357
- **Award type:** 3
- **Project period:** 2021-04-05 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842114

## Citation

> US National Institutes of Health, RePORTER application 10842114, Postnatal Oxytocin Treatment and Cognitive Function in FragileX (3R01HD101642-03S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10842114. Licensed CC0.

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