Behavioural, biochemical and functional phenotyping of chronic exposure to chlordecone in mice

Background

Chlordecone (CLD) is a persistent organochloride pesticide formerly used against banana weevil. It is detectable in blood samples from a large proportion of the population in the French Caribbean Islands. Several experimental studies have demonstrated acute neurotoxicity of CLD, but the effect of a subchronic exposure to CLD remains to be studied.

Methods

Young adult male mice were injected intraperitoneally with 3 mg/kg CLD (n=34) or vehicle (n=22), twice a week, for eight weeks. Behavior, regional brain accumulation, and effects on the dopaminergic system were studied. In addition, functional ultrasound imaging (fUSi) was used to probe the visual, somatosensory and dopaminergic pathways.

Results

CLD was detected in all brain regions (5-15 mg/kg) after two-month exposure, without any marked impact on behavior (anxiety, motor coordination, memory). The dopaminergic system was mostly unaffected, despite slight decreases in the number of TH-positive neurons and the expression of VMAT2, quantified in a subset of animals. fUSi highlighted a decreased response to the visual stimulation in CLD-exposed animals, in contrast to the sensorimotor response, which was found unaltered.

Conclusion

The two-month-long, systemic, exposure to an intermediate dose of CLD resulted in a mostly unaffected phenotype, with a normal behavior and a largely intact dopaminergic system. Interestingly, functional ultrasound imaging was able to detect an altered visual response, which has also been noted in Parkinson’s disease. This study position functional ultrasound imaging as a promising technique to capture early signs of neurotoxicity, opening up opportunities for “toxico-fUS” in the field of neurotoxicology.

Highlights

High CLD neurotropism confirmed in mice by LC-MS/MS.

Sub-chronic chlordecone exposure suggests possible early signs of parkinsonism.

Functional UltraSound reveals impairment of brain areas linked to vision and hearing.