| Neurochemical Characterization of A53T-alpha-synuclein and 6-OHDA Rat Models for Parkinson’s Disease through Animal PET Imaging Analysis |
Junhyung Kim1
, Hyung Ho Yoon1, Jin Hwa Chung2, Seok Ho Hong1, Sang Ryong Jeon1 |
1Department of Neurosurgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
2Convergence Medicine Research Center, Asan Institute for Life Sciences, Seoul, Korea |
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Received: June 3, 2024; Revised: January 20, 2025 Accepted: February 12, 2025. Published online: February 17, 2025.
*Junhyung Kim and Hyung Ho Yoon contributed equally to this work. |
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| ABSTRACT |
Objective
: In preclinical research of Parkinson’s disease, several rodent models, notably the classical 6-hydroxydopamine (6-OHDA) model and the A53T-alpha-synuclein model, have been widely used, yet their distinct neurochemical characteristics in conjunction with behavioral and histopathological changes have been scarcely documented.
Methods
: We examined the two rat models of Parkinson’s disease and characterized them using [18F]FP-CIT animal PET imaging. The 6-OHDA model (n=10) was induced by unilateral injection of 6-OHDA into the middle forebrain bundle, while the A53T-alpha-synuclein model (n=10) was mediated by the adeno-associated viral vectors injected into the substantia nigra. We hypothesized that these models would present differential neurochemical profiles, which could reflect their behavioral and histopathological features and potentially serve as a supplementary tool for evaluating the outcomes of interventions in animal experiments.
Results
: The striatum showed decreased PET uptake on the affected side compared to the unaffected control side, which was highly correlated with the stepping behaviors (R = 0.854 [95% CI, 0.606 to 0.951]). The decrease in striatal PET uptake was more pronounced in the 6-OHDA model than in the A53T-alpha-synuclein model: the 6-OHDA model exhibited a 60% [95% CI, 48% to 65%] decrease in the affected side compared the control side, while the A53T-alpha-synuclein model exhibited a 20% [95% CI, -16% to 47%] decrease. Interestingly, PET uptake in the forebrain cortical region, including the motor cortex, was exclusively decreased in the 6-OHDA model (p = 1.0×10-4 and p = 1.2×10-3, respectively), indicating that 6-OHDA model is affected not only in the nigrostriatal system but also in other cortical regions. Conversely, the A53T-alpha-synuclein model showed no significant alterations in these cortical regions.
Conclusion
: Although the A53T-alpha-synuclein model demonstrates less definitive behavioral changes compared to the 6-OHDA model, it presents a more confined pathophysiological representation of Parkinson’s disease and may be better suited for evaluating certain therapeutic interventions when utilized with adequate neurochemical characterization. |
| Key Words:
Parkinson’s disease · A53T-alpha-synuclein · 6-hydroxydopamine (6-OHDA) · Positron emission tomography (PET) imaging · dopamine transporter (DAT) imaging |
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