ABSTRACT 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 &mgr;‐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. HIGHLIGHTSMPTP mouse model for PD mimics trabecular bone loss seen in the human subjects.MPTP‐induced loss of bone mass is due to decreased bone formation and increased bone resorption.MPTP mouse model of PD can be used for preclinical therapeutic investigations to counter the bone loss in PD.
Shaheen Ali, Govindraj Ellur, Md. Touseef Khan
Toxicology and Applied Pharmacology