Neonatal testosterone exposure modulates exploration and object avoidance without exacerbating autism-like behavior...

Area of Science:

• Neuroscience
• Genetics
• Behavioral Science

Background:

• Autism spectrum disorder (ASD) prevalence is rising, with higher incidence in males, suggesting gene-environment interactions involving sex hormones.
• Prenatal testosterone exposure is a potential risk factor for ASD, but experimental evidence in genetically predisposed models is limited.

Purpose of the Study:

• To investigate the effects of neonatal testosterone administration on the behavior of Shank3b mutant mice, which model a genetic predisposition to ASD.
• To determine if early testosterone exposure influences ASD-like behaviors in conjunction with genetic background and sex.

Main Methods:

• Neonatal Shank3b(-/-) and wild-type mice of both sexes received testosterone or vehicle on postnatal day 1.
• Behavioral phenotyping was conducted during adolescence and adulthood, assessing ASD-like behaviors, object avoidance, self-grooming, marble burying, vertical exploration, and locomotor activity.

Main Results:

• Neonatal testosterone administration did not affect ASD-like behaviors in Shank3b(-/-) mice.
• Testosterone-treated mice exhibited increased object avoidance in adolescence and reduced vertical exploration and locomotor activity in adulthood.
• Shank3b(-/-) mice displayed increased self-grooming, reduced marble burying, and decreased vertical exploration compared to wild-type controls.

Conclusions:

• Neonatal testosterone exposure primarily affects object avoidance and exploration, not core ASD-like behaviors in this genetic model.
• Early testosterone exposure, sex, and Shank3b deficiency show limited synergistic effects on the later-life ASD-like phenotype.