The 6-OHDA Model of Parkinson’s Disease: Mechanisms, Applications, and Limitations

Abstract

Parkinson's disease (PD) is the second most prevalent progressive neurodegenerative disorder, in which the dopaminergic neurons are lost. Genetic and environmental factors are involved in the onset of PD. Symptoms such as tremor, balance problems, nerve pain, muscle stiffness, and mental issues are the most common. Despite the progress made in the understanding of the features of PD, the precise mechanisms responsible for the neuronal degeneration are not well understood. Consequently, animal models such as the 6-hydroxydopamine (6-OHDA) rodent models play a crucial role in studying mechanisms of neurodegeneration and developing therapeutic approaches. The models are made by stereotactic injection of 6-OHDA into striatum to mimic key features of human PD by destroying dopaminergic neurons. The mechanisms, applications and limitations of the 6-OHDA model were explored. Furthermore, analysis indicated that 6-OHDA selectively causes oxidation stress and impairment of mitochondrial function in dopaminergic neurons, thus mimicking various motor symptoms of PD. The acute toxicity and the absence of α-synuclein aggregation and Lewy body formation indicate that it does not recapitulate non-motor symptoms of human PD significantly. Overall, 6-OHDA can still be considered a useful model for preclinical testing of therapeutics. However, aspects of PD pathology such as aggregation of α-synuclein and disease progression as well as non-motor changes, are not well represented. Further work is needed in establishing more clinically simultaneous models or using genetic and α-synuclein-based models in combination with the 6-OHDA model to enhance translational results.