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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.

Till now monocrotophos (MCP) has been addressed as a neurotoxic stressor. Limited studies investigate its aftermath on bone pathologies. Given the fact that MCP is a propensely used insecticide in developing countries, this study investigates its potential to mirror osteoporotic features and bone loss incurred in a rodent model. Briefly, Swiss albino mice were orally gavaged daily with varying doses of MCP for 8 weeks. Musculoskeletal changes were analyzed through micro-computed tomography and histology. A series of in vitro and ex vivo cell culture experiments were performed on MC3T3E-1 and primary osteoclast cultures. Results highlight that oral gavaging with MCP causes bone loss from the cortico-trabecular interface by decreasing the osteoblast and increasing the osteoclast number. Results from in vitro studies establish that MCP treatment increases the TRAP-positive multinucleated cell number during osteoclast differentiation. Ex-vivo experiments with MCP-treated animal sera further substantiate the in vivo claims with significant decreases seen in cell viability, proliferation, mineralization and differentiation studies. In conclusion MCP induces osteoclastogenesis (bone loss) on direct stimulation and alters the circulating factors in MCP-treated serum. Holistically, this work would be of potential significance to patients suffering from pesticide induced osteoporosis.

Bone loss is a non-motor symptom of Parkinson's disease (PD). It is unclear whether a patient's immobility or the endocrine changes in the body causes bone deterioration. To address this issue, we used an animal model of the disease where Swiss albino mice were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on day 1 and were left untreated for eight weeks. Behavioral phenotypes of PD, and striatal acetylcholinesterase and dopamine levels were measured. Cortical and trabecular bones were assessed by μ-CT and histology. Gene expression studies were done through quantitative real-time PCR. Effect of MPP+ and MPTP-treated mice serum on MC3T3E-1, SH-SY5Y, and primary osteoclast cells were also studied. Our results demonstrated that MPTP treatment leads to PD like symptoms. It shows a loss of trabecular bone mass and quality by decreasing osteoblast and increased osteoclast number and activity. This effect was accompanied by reduced osteogenic and elevated osteoclastogenic genes expression. While MPP+ had a cytotoxic effect on dopaminergic neurons, it did not affect bone cells. However, ex-vivo treatment of the serum from MPTP-treated mice decreased osteoblastogenesis and increased osteoclastogenesis in cell culture. In conclusion, our study suggests that MPTP-induced parkinsonian features in mice leads to trabecular bone loss by decreased bone formation and increased bone resorption due to changes in the serum circulating factors. This study characterizes the microarchitectural and cellular changes in the skeleton of a mouse model of PD that can be further utilized to investigate therapeutic avenues to treat bone loss in PD patients.

Our earlier study had shown that low concentrations of monocrotophos (MCP) elicited dopaminergic features of Parkinson’s disease (PD) in the nematode Caenorhabditis elegans. In the present study, the effect of low doses of MCP on the striatal dopaminergic neurons was investigated using the mouse model system. MCP was initially screened for its ability to cause any neurobehavioral deficits and alterations in the dopaminergic system in Swiss albino mice, aged 8 weeks and weighing 25–30 g, with repeated doses at 0.3 and 0.6 mg/kg body weight (b.w.)/day for 7 days and 30 days. Mice were treated with four intraperitoneal injections for every 2 h with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at the dosage of 14 mg/kg b.w. MCP was administered to these mice at the above-mentioned doses for 7 days. Mice administered with MCP alone revealed a significant ( p < 0.05) reduction in the dopamine (DA) content at both 7 and 30 days and showed a significant ( p < 0.05) increase in neurobehavioral deficits. Interestingly, when MCP was administered for 7 days to MPTP-treated mice, further significant decrease in both DA content and increase in neurobehavioral deficits were apparent. The extent of reactive oxygen species and lipid peroxidation were markedly increased, while the ratio of reduced to oxidized glutathione levels were significantly decreased ( p < 0.05) in the treated mice as compared to the control. Significant histopathological alterations and a marked reduction in the number of tyrosine hydroxylase positive cells were evident in striatum of mice treated with higher doses of MCP. These changes were comparable to that seen in mice treated with MPTP and post-administered lower doses of MCP. Our findings suggest that MCP per se has the propensity to induce pathological changes in the dopaminergic neurons as well as augment the degeneration in a compromised nigrostriatal system such as that in PD.