Kim Junhyung, Yoon Hyung Ho, Jung Jin Hwa, Hong Seok Ho, Jeon Sang Ryong
Department of Neurosurgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Convergence Medicine Research Center, Asan Institute for Life Sciences, Seoul, Korea.
J Korean Neurosurg Soc. 2025 Sep;68(5):541-550. doi: 10.3340/jkns.2024.0109. Epub 2025 Feb 17.
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.
We examined the two rat models of Parkinson's disease and characterized them using [18F]fluoropropyl-carbomethoxyiodophenyltropane (FP-CIT) animal positron emission tomography (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.
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% confidence interval [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% decrease (95% CI, 48% to 65%) in the affected side compared the control side, while the A53T-alpha-synuclein model exhibited a 20% decrease (95% CI, -16% to 47%). 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.
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.
在帕金森病的临床前研究中，几种啮齿动物模型，特别是经典的6-羟基多巴胺（6-OHDA）模型和A53T-α-突触核蛋白模型，已被广泛使用，但其独特的神经化学特征以及行为和组织病理学变化却鲜有记录。
我们研究了两种帕金森病大鼠模型，并使用[18F]氟丙基-甲氧羰基碘代苯基托烷（FP-CIT）动物正电子发射断层扫描（PET）成像对其进行表征。6-OHDA模型（n = 10）通过将6-OHDA单侧注射到中脑前束诱导，而A53T-α-突触核蛋白模型（n = 10）由注射到黑质的腺相关病毒载体介导。我们假设这些模型将呈现不同的神经化学特征，这可以反映它们的行为和组织病理学特征，并有可能作为评估动物实验中干预结果的补充工具。
与未受影响的对照侧相比，纹状体在受影响侧的PET摄取减少，这与步进行为高度相关（R = 0.854；95%置信区间[CI]，0.606至0.951）。6-OHDA模型纹状体PET摄取的减少比A53T-α-突触核蛋白模型更明显：与对照侧相比，6-OHDA模型受影响侧减少了60%（95%CI，48%至65%），而A53T-α-突触核蛋白模型减少了20%（95%CI，-16%至47%）。有趣的是，包括运动皮层在内的前脑皮质区域的PET摄取仅在6-OHDA模型中降低（分别为p = 1.0×10-4和p = 1.2×10-3），表明6-OHDA模型不仅在黑质纹状体系统中受到影响，而且在其他皮质区域也受到影响。相反，A53T-α-突触核蛋白模型在这些皮质区域没有显示出明显变化。
尽管与6-OHDA模型相比，A53T-α-突触核蛋白模型表现出的明确行为变化较少，但它呈现出更局限的帕金森病病理生理表现，并且在进行充分的神经化学表征时，可能更适合评估某些治疗干预措施。
