Autism-like phenotype across the lifespan of Shank3B-mutant mice of both sexes.

Researchers studied mice with autism-like traits throughout their lives, from young to old age. They found that some autism symptoms changed as the mice got older - social problems appeared mainly in older male mice, anxiety was highest in middle age, and repetitive behaviors stayed consistent. Female mice showed more movement difficulties. This suggests autism traits may change over a person's lifetime and affect males and females differently.

This study examined autism-like behaviors across the lifespan in Shank3B-mutant mice, a genetic model of autism spectrum disorder. Researchers tested 135 mice of both sexes at three age points (adolescence, adulthood, old age) for social behavior, repetitive behaviors, anxiety, and motor activity. Key findings included age-specific social deficits in older male mice, peak anxiety in adulthood, and consistent repetitive behaviors and reduced activity throughout life. Female mice showed more pronounced reductions in exploratory behavior.

The study demonstrates that autism-like traits change with age in this mouse model, with some effects being sex-specific, though overall effect sizes were small.

Findings suggest autism symptoms may change across the lifespan with sex-specific patterns. This supports the need for longitudinal monitoring and potentially different intervention approaches at different life stages, particularly considering sex differences in presentation.

Study used a single mouse model which may not represent all autism presentations. Sample sizes for age groups were relatively small. Effect sizes were described as small, limiting clinical translation potential.

High heritability (80-90%) of the autism spectrum disorder (ASD) and sex-biased incidence (3-4 times more boys than girls) suggest the roles of genetic predisposition and sex in the etiopathogenesis of the disorder. As ASD is commonly diagnosed in early childhood, most of the research is focused on children, yet animal research predominantly uses adult-aged animals. The effect of aging on the core and secondary ASD symptomatology is understudied, both in patients and animal models of ASD. To investigate the effect of aging on sociability, repetitive behavior, exploration, locomotor activity, anxiety-like behavior, and object-avoidance behavior, behavioral phenotyping was conducted in Shank3B(n = 67) and C57BL/6J wild-type (WT, n = 68) mice of both sexes (female n = 70, male n = 65) in adolescence (1-2 months of age, n = 42), adulthood (3-6 months of age, n = 40), and old age (12-18 months of age, n = 53).

Social deficits were observed only in old Shank3Bmales. Anxiety-like behavior peaked in adulthood with Shank3Bmice roughly 20% more anxious than controls. Repetitive grooming and object-induced avoidance behavior were twice more prevalent in Shank3Bmice consistently across the lifespan. Hypoactivity (20% less distance moved) and reduced exploration (30% less rearing behavior) were recorded in Shank3Bmice and were more prevalent in female animals (30% less rearing behavior).

Data were analyzed using the Three-way ANOVA (genotype, sex, age), followed by a posthoc Bonferroni correction to compare respective subgroups. Present study shows that aging affects ASD-like phenotype in the Shank3B-mutant mouse model, even though the effect size seems to be small. The mechanisms underlying these partially sex-specific effects should be the subject of further research with potential translational implications.