Logo image
Back
5.36 Modeling Striatal Enlargement and Associated Behaviors in the Developing Mouse Brain
Abstract   Peer reviewed

5.36 Modeling Striatal Enlargement and Associated Behaviors in the Developing Mouse Brain

Jordan J. Samuel, Maya M. Evans, Robert J. Taylor and Hanna E. Stevens
Journal of the American Academy of Child and Adolescent Psychiatry, Vol.63(10), pp.S267-S267
10/2024
DOI: 10.1016/j.jaac.2024.08.357

View Online

Abstract

Objectives Prior studies highlight striatal enlargement for some individuals with ASD. This pilot study aimed to create a striatal-overgrowth mouse model for future neurodevelopmental studies examining effects on behavior. We used 2-chloro-5-hydroxyphenylglycine (CHPG), an agonist of mGluR5, a receptor regulating proliferation of the ventral forebrain, including the striatum, in early development. We compared different routes of CHPG administration, assessing their efficacies at inducing striatal enlargement and their effects on striatal-dependent behavior in developing mice. Methods CHPG administration occurred on embryonic day 13 (E13) through either: 1) indirect delivery to embryonic brain through maternal intraperitoneal (IP) injection; or 2) embryonic intracerebroventricular (ICV) injections to directly target embryonic brain. Saline injection served as the control condition. Brains from offspring mice were collected at E17, sectioned, and stained with 4′,6-diamidino-2-phenylindole (DAPI). Unbiased stereology was utilized to quantify striatal volume, total cell count, and total cell density. In additional litters, offspring were born and tested for ASD-related behavioral changes on motor function in the open field task as juveniles and on open field, a rotarod motor learning task, and a stereopy task as adults. Results CHPG IP-injected mice did not display striatal enlargement or increased cell count compared to saline-injected mice (n = 7, 8; p > .05). Juvenile CHPG IP-injected offspring showed no behavioral changes (n = 5, 5; p > .05). Notably, separate adult CHPG IP-injected littermates trended toward a shorter distance traveled in the open field compared to controls (n = 7, 7, p = .09). The same groups showed no difference in rotarod motor learning ( p > .05). In contrast, pilot work suggests that CHPG ICV injections caused increased striatal cell number, but additional offspring brain and behavior analyses are in progress. Conclusions We did not find an effect of maternal IP CHPG injections on the embryonic striatum, However, we predict that embryonic CHPG ICV will induce striatal enlargement of mice. Given this, ASD-related behavioral deficits are expected in CHPG ICV-treated mice compared to controls. This study aids in elucidating the neurodevelopmental basis for ASD and possible treatment targets relevant to children.

Details

Metrics

29 Record Views
Logo image