Differential impact of dose-range glyphosate on locomotor behavior, neuronal activity, glio-cerebrovascular structures, and transcript regulations in zebrafish larvae

• Published in: Chemosphere (Oxford) 2021-03, Vol.267, p.128986, Article 128986
• Main Authors: Forner-Piquer, Isabel, Faucherre, Adèle, Byram, Julia, Blaquiere, Marine, de Bock, Frederic, Gamet-Payrastre, Laurence, Ellero-Simatos, Sandrine, Audinat, Etienne, Jopling, Chris, Marchi, Nicola
• Format: Article
• Language: English
• Subjects: Animals; Behavior; Electrophysiology; Glycine - analogs & derivatives; Glyphosate; Herbicides - toxicity; Humans; Larva - genetics; Life Sciences; Microglia; Neurons and Cognition; Neurovascular; Prospective Studies; Toxicology; Zebrafish; Zebrafish - genetics
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2020.128986

The presence of glyphosate represents a debated ecotoxicological and health risk factor. Here, zebrafish larvae were exposed, from 1.5 to 120 h post-fertilization, to a broad concentration range (0.05–10.000 μg/L) of glyphosate to explore its impact on the brain. We evaluated morphology, tracked locomotor behavior and neurophysiological parameters, examined neuro-glio-vascular cell structures, and outlined transcriptomic outcomes by RNA sequencing. At the concentration range tested, glyphosate did not elicit gross morphological changes. Behavioral analysis revealed a significant decrease in locomotor activity following the exposure to 1000 μg/L glyphosate or higher. In parallel, midbrain electrophysiological recordings indicated abnormal, and variable, spike activity in zebrafish larvae exposed to 1000 μg/L glyphosate. Next, we asked whether the observed neurophysiological outcome could be secondary to brain structural modifications. We used transgenic zebrafish and in vivo 2-photon microscopy to examine, at the cellular level, the effects of the behavior-modifying concentration of 1000 μg/L, comparing to low 0.1 μg/L, and control. We ruled out the presence of cerebrovascular and neuronal malformations. However, microglia morphological modifications were visible at the two glyphosate concentrations, specifically the presence of amoeboid cells suggestive of activation. Lastly, RNAseq analysis showed the deregulation of transcript families implicated in neuronal physiology, synaptic transmission, and inflammation, as evaluated at the two selected glyphosate concentrations. In zebrafish larvae, behavioral and neurophysiological defects occur after the exposure to high glyphosate concentrations while cellular and transcript signatures can be detected in response to low dose. The prospective applicability to ecotoxicology and the possible extension to brain-health vulnerability are critically discussed. [Display omitted] •In zebrafish larvae, behavioral and brain electrophysiological changes elicit at high glyphosate concentrations.•Neurological outcomes are not associated with structural neuro-vascular or muscular malformations.•Morphological signs of microglia activation are reported after exposure to low and high glyphosate concentrations.•Transcriptomic analysis reveals the deregulation of candidate pathways, possibly extending to neuronal vulnerability.