Abstract
3.28 Inducing Striatal Overgrowth in Mice to Model Autism-Linked Neurodevelopmental Changes
Journal of the American Academy of Child and Adolescent Psychiatry, Vol.64(10 Suppl), p.S230
10/2025
DOI: 10.1016/j.jaac.2025.08.238
Abstract
Objectives
Striatal enlargement has been observed in a subset of individuals with ASD and may contribute to core symptomatology. This study aimed to develop a novel mouse model of striatal overgrowth through in utero administration of 2-chloro-5-hydroxyphenylglycine (CHPG), an mGluR5 agonist known to stimulate embryonic neural stem cell proliferation only in the ventral forebrain that becomes the striatum. We evaluated whether CHPG-induced striatal enlargement alters postnatal behavior relevant to ASD.
Methods
On embryonic day 13 (E13), CHPG or saline was administered via intracerebroventricular (ICV) injection to directly target the mouse embryonic brain. Brains were collected at E17 and sectioned, and all cell nuclei were stained with DAPI. Stereological analyses quantified striatal volume, total cell count, and cell density. Additional litters were delivered via C-section and raised to postnatal stages for behavioral testing. Juvenile mice were evaluated using the open field test. Adult offspring completed a behavioral battery including open field, rotarod motor learning, water T-maze habit and reversal learning, and amphetamine (AMPH)-induced stereotypy assays. Sample sizes ranged from n = 6-12 per group.
Results
CHPG ICV administration led to a significant 13.1% increase in embryonic striatal cell density compared to controls (p < .05), without corresponding changes in striatal volume or cell number. Juvenile mice showed no significant differences in locomotor or anxiety-like behavior. In adulthood, CHPG-treated mice displayed a greater increase in large circling but a lack of increase in self-circling behavior following AMPH administration (p < .05), which resulted in a trend increase in total circling compared to controls. They also showed a trend decrease in reversal learning. No rotarod changes were observed. Assessments of adult striatal structure are ongoing.
Conclusions
These findings provide the first direct evidence that prenatal activation of mGluR5 via CHPG ICV injection induces striatal cellular overgrowth and leads to enduring changes in striatal-dependent behavior. This model offers a tractable platform for exploring mechanisms linking early striatal overgrowth to ASD-relevant behavioral phenotypes and may inform future therapeutic targets.
Details
- Title: Subtitle
- 3.28 Inducing Striatal Overgrowth in Mice to Model Autism-Linked Neurodevelopmental Changes
- Creators
- Jordan J. SamuelMaya M. EvansRobert J. TaylorHanna E. Stevens
- Resource Type
- Abstract
- Publication Details
- Journal of the American Academy of Child and Adolescent Psychiatry, Vol.64(10 Suppl), p.S230
- DOI
- 10.1016/j.jaac.2025.08.238
- ISSN
- 0890-8567
- eISSN
- 1527-5418
- Publisher
- ELSEVIER SCIENCE INC
- Grant note
- NIMH: R01MH122485-01
Supported by NIMH Grant R01MH122485-01
- Language
- English
- Date published
- 10/2025
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9985014901802771
Metrics
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