Persistent and Dose-Dependent Neural and Metabolic Gene Expression Changes Induced by Transient Citalopram Exposure...

Area of Science:

• Environmental toxicology
• Developmental neurobiology
• Molecular toxicology

Background:

• Selective serotonin reuptake inhibitors (SSRIs) like citalopram are increasingly found in aquatic environments.
• Developmental exposure to SSRIs can cause neurotoxicity, but long-term gene expression changes after limited exposure are poorly understood.

Purpose of the Study:

• To investigate the persistent effects of early-life citalopram exposure on gene expression in zebrafish embryos.
• To determine the dose-response relationship and affected pathways following transient SSRI exposure.

Main Methods:

• Zebrafish embryos were exposed to citalopram hydrobromide (0.03–250 μg/L) from 2 to 24 hours post-fertilization.
• Following citalopram removal, embryos were developed until 48 hours post-fertilization.
• Whole-embryo RNA sequencing was performed, followed by gene set enrichment and overrepresentation analyses.

Main Results:

• A non-linear dose-response was observed, with the lowest dose (0.03 μg/L) inducing the most differentially expressed genes.
• Low doses affected metabolic, developmental, and synaptic genes, while higher doses induced oxidative stress, apoptosis, and repressed glutamate receptors.
• All doses indicated alterations in synaptic and neurotransmitter pathways, suggesting persistent neurodevelopmental impacts.

Conclusions:

• Transient, low-level exposure to citalopram during early development can lead to persistent, long-term changes in embryonic gene expression.
• These findings highlight the potential for environmental SSRIs to cause lasting neurodevelopmental effects in aquatic organisms.