Psychopharmacology · 2025
Optimizing prenatal valproic acid exposure in zebra finches to model autism-related phenotypes.
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Pogány Ákos, Tewelde Estifanos Ghebrihiwet, Morvai Boglárka, Zachar Gergely
Аннотация
RATIONALE: Rodent models dominate autism spectrum disorder (ASD) research, yet their translational validity is limited for a heterogeneous condition with complex social-vocal phenotypes.
OBJECTIVES: To evaluate the zebra finch (Taeniopygia guttata) - a highly social, vocal-learning songbird - as an ASD model by adapting embryonic valproic acid (VPA) exposure and identifying dose-timing conditions that preserve viability while perturbing social behavior.
METHODS: We used a 3 × 3 design crossing VPA dose (0, 0.3, 0.6 µmol/egg) with manipulation day (incubation days 8-10). Hatching success, post-hatching survival, growth, and social behavior in a bird-adapted three-chamber test were quantified with mixed-effects models (binomial/Cox/linear/negative binomial, beta-binomial).
RESULTS: Hatching success decreased at 0.6 µmol and with day-8 injections; day-9 performed best. Post-hatching survival was lower at 0.3 µmol versus controls (limited inference for 0.6 µmol due to small n). Growth showed dose×sex interactions: females at 0.6 µmol were lighter with shorter tarsi; wings showed a similar tendency. In sociability (phase 1), time-based measures were unchanged, 0.6-µmol birds made more approaches to the closest perch, while day-8 birds approached less than day-9. In phase 2, time on the familiar-side closest perch showed a day×sex interaction (day-8 females spent less time than day-8 males), and approaches to that perch increased at 0.6 µmol. Overall sociability (combined closest perches) and total activity did not differ by group.
CONCLUSIONS: Embryonic VPA in zebra finches yields selective, partly sex-dependent developmental and social effects. Zebra finches remain promising; day-9 intermediate doses (~ 0.35-0.50 µmol) warrant follow-up to map dose-response and balance viability with behavioral detectability.
OBJECTIVES: To evaluate the zebra finch (Taeniopygia guttata) - a highly social, vocal-learning songbird - as an ASD model by adapting embryonic valproic acid (VPA) exposure and identifying dose-timing conditions that preserve viability while perturbing social behavior.
METHODS: We used a 3 × 3 design crossing VPA dose (0, 0.3, 0.6 µmol/egg) with manipulation day (incubation days 8-10). Hatching success, post-hatching survival, growth, and social behavior in a bird-adapted three-chamber test were quantified with mixed-effects models (binomial/Cox/linear/negative binomial, beta-binomial).
RESULTS: Hatching success decreased at 0.6 µmol and with day-8 injections; day-9 performed best. Post-hatching survival was lower at 0.3 µmol versus controls (limited inference for 0.6 µmol due to small n). Growth showed dose×sex interactions: females at 0.6 µmol were lighter with shorter tarsi; wings showed a similar tendency. In sociability (phase 1), time-based measures were unchanged, 0.6-µmol birds made more approaches to the closest perch, while day-8 birds approached less than day-9. In phase 2, time on the familiar-side closest perch showed a day×sex interaction (day-8 females spent less time than day-8 males), and approaches to that perch increased at 0.6 µmol. Overall sociability (combined closest perches) and total activity did not differ by group.
CONCLUSIONS: Embryonic VPA in zebra finches yields selective, partly sex-dependent developmental and social effects. Zebra finches remain promising; day-9 intermediate doses (~ 0.35-0.50 µmol) warrant follow-up to map dose-response and balance viability with behavioral detectability.