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Karyn Robichaud

Laboratory Toxicology

Poster Session




Venlafaxine exposure alters mitochondrial respiration and mitomiR abundance in zebrafish brains


Wastewater treatment plant (WWTP) effluent containing pharmaceuticals is released into freshwater ecosystems where it can have negative effects on fish. Venlafaxine (VFX), an SNRI antidepressant detected in WWTP effluent, impacts fish metabolism and can accumulate in fish tissues. Due to its potential to accumulate in mitochondria, VFX may have effects on zebrafish brain mitochondrial respiration. For example, in rat brains, VFX impacts activity of mitochondrial oxidative phosphorylation complexes. In addition, since mitochondria contain their own DNA, mechanisms that regulate mitochondrial gene expression may play a role in responding to metabolic stressors like VFX. MicroRNA (small RNA molecules) regulate mitochondrial gene expression post-transcriptionally and are known to translocate into the mitochondria. Here, they can regulate expression of mitochondrial mRNAs and have predicted targets in fish. This study sought to identify if VFX exposure impacts mitochondrial respiration in zebrafish brains at environmentally relevant concentrations (1 ug/L) and determine if mitochondrial microRNA (mitomiRs) are differentially abundant with VFX exposure. We found that in vitro exposure to VFX caused a decrease in mitochondrial respiration at below environmentally relevant concentrations of VFX. To identify whether these effects also occur in vivo, zebrafish were exposed to 1 ug/L VFX for 0, 1, 6, 12, 24 and 96 hours. We found no changes to mitochondrial respiration indices at any time points. However, we also quantified mitomiRs (dre-miR-301a-5p, dre-miR-301b-3p, dre-miR-301c-3p) that were bioinformatically predicted to regulate mitochondrial cytochrome c oxidase subunit I (COI), and saw changes in their abundance based on exposure to VFX, sex, and time sampled. Overall, VFX had demonstrated effects in vivo, which may have been mitigated during in vivo exposure due to the ability of the fish to respond on a whole organism level through mechanisms like mitomiR regulation.

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