Chlorpyrifos Exposure Induces Parkinsonian Symptoms and Associated Bone Loss in Adult Swiss Albino Mice

Prenatal and early life exposure of chlorpyrifos (CPF), a widely used pesticide, is known to cause neuronal deficits and Parkinson's disease (PD). However, data about the effect of its exposure at adult stages on PD-like symptoms and associated bone loss is scanty. In the present study, we investigated the impact of CPF on the behavioral alterations seen in PD using adult Swiss albino mice. PD is often associated with bone loss. Hence, skeletal changes were also evaluated using micro-computed tomography and histology. MPTP was used as a positive control. Cell culture studies using MC3T3E-1, SHSY5Y, and primary osteoclast cultures were done to understand the cellular mechanism for the behavioral and skeletal changes. Our results showed that CPF treatment leads to PD-like symptoms due to the loss of dopaminergic neurons. Moreover, CPF has a deleterious effect on the trabecular bone through both indirect changes in circulating factors and direct stimulation of multinucleate osteoclast cell formation. The impact on the bone mass was even stronger than MPTP. In conclusion, this is the first report demonstrating that CPF induces parkinsonian features in adult Swiss albino mice and it is accompanied by loss of trabecular bone.