Behavioral and molecular insights into anxiety in ube3a and fmr1 zebrafish models of autism spectrum disorders.

Scientists studied anxiety behaviors in zebrafish with genetic changes that cause Angelman syndrome and Fragile X syndrome. They found that fish with different genetic changes showed different patterns of anxiety at different life stages. Young fish with Fragile X changes were less active, but became hyperactive as adults. Fish with Angelman changes were normal when young but less active as adults.

This zebrafish study examined anxiety-like behaviors in models of Angelman syndrome (ube3a mutations) and Fragile X syndrome (fmr1 mutations). Using light-dark and novel tank diving tests across larval and adult stages, researchers found distinct developmental patterns: ube3a mutants showed normal larval behavior but reduced activity and exploration in adulthood, while fmr1 mutants displayed reduced activity as larvae but hyperactivity and lower anxiety as adults. RNA sequencing identified molecular pathways underlying these behavioral differences. The study demonstrates the importance of using multiple behavioral assays and developmental timepoints to understand autism-related genetic mutations.

Findings suggest anxiety presentations in autism-related genetic conditions may change across development. This highlights the importance of age-appropriate assessments and interventions, and supports research into developmental timing of therapeutic approaches.

Animal model study using zebrafish; sample sizes not reported; unclear how findings translate to human autism conditions; limited detail on molecular pathway analysis provided in abstract.

Angelman syndrome and Fragile X syndrome are neurodevelopmental disorders (NDDs) caused by mutations in the UBE3A and FMR1 genes, respectively. However, they share common features such as cognitive and motor deficits, anxiety, and impaired social behavior. In this study, we utilized zebrafish as an animal model to investigate the anxiety-like effects of mutations in these genes across larval and adult stages, employing two widely used behavioral assays: the light-dark test (LDT) and the novel tank diving test (NTT). We conducted detailed analyses of anxiety-like behaviors and exploration patterns in ube3a and fmr1 mutant fish, comparing both genotypes to their respective wild-type (WT) counterparts.

Importantly, we analyzed RNA sequencing data from both larvae and adults to better understand the molecular pathways associated with the anxiety profiles of these genotypes. Our results show that larval ube3a mutants did not exhibit significant difference in the LDT compared to the WT; however, they showed significant reductions in distance travelled, velocity, and light-zone exploration during adult stages. In contrast, fmr1 mutants exhibited reduced locomotor activity in the LDT at larval age and hyperactivity and lower anxiety-like behaviors in adulthood. We identify key genes implicated in these behaviors and shared pathways that warrant further investigation for the development of therapies addressing ASD.

Ultimately, our results highlight the importance of using different behavioral assays, such as the LDT and NTT, combined with omics approaches like RNA sequencing, to discern the distinct behavioral phenotypes caused by genetic mutations and to create opportunities for better understanding NDDs.