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Keywords

neurodevelopment, autism, zebrafish, redox

Abstract

The optic tectum (OT), the non-mammalian counterpart of the mammalian superior colliculus (SC), integrates multisensory information and orchestrates behavioral responses such as reflexive movements and attention shifts. It is localized in the midbrain, where anterior-posterior patterning is regulated by transcription factors dependent on proper endogenous H2O2 levels. Recent studies have implicated the OT/SC and early redox imbalance in neurodevelopmental disorders such as autism spectrum disorder (ASD). Given the importance of H2O2 in midbrain development, we are investigating how redox perturbations may lead to atypical OT circuitry development and, subsequently, result in aberrant behavioral phenotypes, similar to those associated with ASD. When we previously exposed zebrafish embryos to valproic acid (VPA), a drug associated with a higher incidence of ASD and known to induce redox stress, we observed hyperactivity and increased anxiety. However, whether these effects are specific to possible redox stress in the OT remains unclear. To address this, we will induce targeted redox changes in the OT using the nitroreductase-metronidazole (NTR-MTZ) system at levels that do not induce apoptosis. Additionally, we will modulate redox effects by inhibiting key redox regulators nrf2a, keap1a, and keap1b. In brief, the transcription factor nrf2a activates antioxidant genes in response to reactive oxygen species (ROS), but is ubiquitinated by keap1a/b when ROS is absent. We anticipate that a nrf2a knockout will potentiate ROS effects, while keap1a/b knockouts will mitigate ROS effects. Subsequent behavioral assays will elucidate the impact of OT-specific redox changes, offering insights into the interplay between redox states, OT development, and behavioral outcomes.

Document Type

Poster

Publication Date

2026-03-26

Language

English

College

Life Sciences

Department

Cell Biology and Physiology

University Standing at Time of Publication

Junior

Exploring the Impact of Redox Perturbations on Optic Tectum Development and Behavior

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Life Sciences Commons

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