The 6-OHDA Model of Parkinson’s Disease: Mechanisms, Applications, and Limitations
DOI:
https://doi.org/10.62051/2v1mqa20Keywords:
Parkinson’s disease; 6-OHDA; Striatum; Substantia nigra; Dopamine neuron.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.
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[1] National Institute of Neurological Disorders and Stroke. (2025, March 5). Parkinson’s disease. National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/health-information/disorders/parkinsons-disease
[2] Linen, S. R., Chang, N. H., Hess, E. J., Stanley, G. B., & Waiblinger, C. (2024). Sensory-behavioral deficits in Parkinson’s disease: Insights from a 6-OHDA mouse model. bioRxiv. https://doi.org/10.1101/2024.06.05.597339 DOI: https://doi.org/10.1101/2024.06.05.597339
[3] Masini, D., Plewnia, C., Bertho, M., Scalbert, N., Caggiano, V., & Fisone, G. (2021). A guide to the generation of a 6-hydroxydopamine mouse model of Parkinson’s disease for the study of non-motor symptoms. Biomedicines, 9(6), 598. https://doi.org/10.3390/biomedicines9060598 DOI: https://doi.org/10.3390/biomedicines9060598
[4] Cui, J., Zhao, D., Xu, M., Li, Z., Qian, J., Song, N., Wang, J., & Xie, J. (2024). Characterization of graded 6-hydroxydopamine unilateral lesion in medial forebrain bundle of mice. Scientific Reports, 14(1). https://doi.org/10.1038/s41598-024-54066-0 DOI: https://doi.org/10.1038/s41598-024-54066-0
[5] Wu, S.-L., Liscic, R. M., Kim, S., Sorbi, S., & Yang, Y.-H. (2017). Nonmotor symptoms of Parkinson’s disease. Parkinson’s Disease, 2017, 1–2. https://doi.org/10.1155/2017/4382518 DOI: https://doi.org/10.1155/2017/4382518
[6] Boix, J., Padel, T., & Paul, G. (2015). A partial lesion model of Parkinson’s disease in mice: Characterization of a 6-OHDA-induced medial forebrain bundle lesion. Behavioural Brain Research, 284, 196–206. https://doi.org/10.1016/j.bbr.2015.01.053 DOI: https://doi.org/10.1016/j.bbr.2015.01.053
[7] Park, S. E., Song, K.-I., Kim, H., Chung, S., & Youn, I. (2018). Graded 6-OHDA-induced dopamine depletion in the nigrostriatal pathway evokes progressive pathological neuronal activities in the subthalamic nucleus of a hemi-parkinsonian mouse. Behavioural Brain Research, 344, 42–47. https://doi.org/10.1016/j.bbr.2018.02.014 DOI: https://doi.org/10.1016/j.bbr.2018.02.014
[8] Cramb, K. M. L., Beccano-Kelly, D., Cragg, S. J., & Wade-Martins, R. (2023). Impaired dopamine release in Parkinson’s disease. Brain, 146(8). https://doi.org/10.1093/brain/awad064 DOI: https://doi.org/10.1093/brain/awad064
[9] Kolacheva, A., Alekperova, L., Pavlova, E., Bannikova, A., & Ugrumov, M. V. (2022). Changes in tyrosine hydroxylase activity and dopamine synthesis in the nigrostriatal system of mice in an acute model of Parkinson’s disease as a manifestation of neurodegeneration and neuroplasticity. Brain Sciences, 12(6), 779. https://doi.org/10.3390/brainsci12060779 DOI: https://doi.org/10.3390/brainsci12060779
[10] Cheung, T. H. C., Ding, Y., Zhuang, X., & Kang, U. J. (2023). Learning critically drives parkinsonian motor deficits through imbalanced striatal pathway recruitment. Proceedings of the National Academy of Sciences, 120(12). https://doi.org/10.1073/pnas.2213093120 DOI: https://doi.org/10.1073/pnas.2213093120
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