Broflanilide induces zebrafish neurobehavioral defects by interfering with synaptic homeostasis

Area of Science:

• Neuroscience
• Environmental Toxicology
• Molecular Biology

Background:

• Broflanilide is a widely used bisamide insecticide.
• Previous research indicated neurotoxicity in zebrafish embryos.
• The behavioral and cellular mechanisms of adult neurotoxicity were largely unknown.

Purpose of the Study:

• To investigate the behavioral and neural impacts of chronic broflanilide exposure in adult zebrafish.
• To elucidate the underlying neural cell mechanisms of broflanilide-induced neurotoxicity.

Main Methods:

• Adult zebrafish were exposed to 5 and 25 μg/L broflanilide for 30 days.
• Neuro-behavioral tests, targeted metabolomics, and single-cell RNA sequencing were employed.
• Analysis focused on synaptic function, neuron loss, and brain cell composition changes.

Main Results:

• Exposure to 25 μg/L broflanilide induced abnormal locomotion and cognitive defects.
• Synaptic homeostasis was disrupted, evidenced by fewer synaptic knobs and neuron loss.
• Metabolomic and single-cell RNA sequencing revealed altered glutathione metabolism, GABAergic synapses, and shifts in brain cell populations (decreased neurons/oligodendrocytes, increased astrocytes).

Conclusions:

• Broflanilide poses a long-term neurotoxic risk to aquatic organisms.
• Neurotoxicity involves synaptic dysfunction and altered brain cell composition.
• Across-cell type transcriptional regulation mediates broflanilide's neurotoxic effects.