Effects of Indoxyl Sulfate on Dopaminergic Neurons and Motor Functions

Abstract

Introduction: Increased levels of indoxyl sulfate (IS), a uremic toxin and a metabolite produced by gut bacteria, are reported in patients
with Parkinson’s disease (PD). However, the effects of IS on dopaminergic neurons and motor functions remain unexplored. In this study,
we investigated whether IS treatment induces PD-related phenotypes such as cell death in dopaminergic neurons and motor function defects
in vitro and in vivo. Materials and Methods: PC12 cells were treated with IS (100 µM) for 24 h, and tyrosine hydroxylase (TH) levels were
measured. In vivo experiments in mice included: (1) short-term treatment with IS (200 mg/kg/d, i. p., or 400 mg/kg/d, p. o., once a day for
5 days) and (2) long-term treatment with IS (200 mg/kg/d, i. p., once a day for 28 days). Control mice received an equal volume of saline.
Motor functions were evaluated using the open field test, pole test, and rotarod test. TH expression in the substantia nigra and striatum regions
of the mouse brain was evaluated using immunohistochemistry and Western blotting. Results: No significant difference in the levels of TH was
observed between the untreated and IS-treated PC12 cells. Further, in vivo studies in mice showed that both, acute and chronic IS treatment,
failed to induce motor deficits and cell death in dopaminergic neurons. Conclusion: Taken together, our results suggest that IS has no effects
on motor functions and dopaminergic neurons.